weiterführende literatur zum lehrbuch...
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Weiterführende Literatur zum Lehrbuch „Biochemie“ (Kapitel 4 – 50) Im Buch ist aus Platzgründen auf die Angabe weiterführender Literatur verzichtet worden. Auskünfte zu den thematischen Schwerpunkten der vier Hauptteile II bis V geben die im Folgenden aufgeführten knapp 1000 einschlägigen Artikel aus wissenschaftlichen Fachzeitschriften. Die Zusammenstellung von Dr. Heike Angerer folgt der Gliederung des Buchs. Über die Lesezeichen-Darstellung (links) können Sie direkt zur Literatur der einzelnen Kapitel springen, aber es ist stets auch die gesamte Literatur hinterlegt (z.B. für einen kompletten Ausdruck). Die Aufstellung enthält überwiegend Review-Artikel der letzten 4 Jahre, in denen der aktuelle Kenntnisstand zu einem ausgewählten Thema von führenden Wissenschaftlern präsentiert wird. Beim Einführungsteil (Kapitel 1 bis 3) haben wir dagegen bewusst auf Spezialliteratur verzichtet; hier sei auf einschlägige Lehrbücher der Biochemie, Molekularbiologie, Genetik und Zellbiologie, die diesen fundamentalen Aspekten breiten Raum widmen, verwiesen. Falls Sie als Leser interessante Artikel finden, die unsere Literatursammlung ergänzen und bereichern könnten, bitten wir um kurze Mitteilung an den Verlag. Werner Müller-Esterl (für die Autoren)Heike Angerer (Bearbeitung für die 2. Auflage)
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Teil II Struktur und Funktion von Proteinen
4 Proteine – Werkzeuge der Zelle
4.1 Liganden binden an Proteine und verändern deren Konformation
Wilson MA, Brunger AT (2000) The 1.0 Å crystal structure of Ca2+-bound calmodulin:
an analysis of disorder and implications for functionally relevant plasticity, J Mol Biol
301, 1237-1256
O'Day DH & Myre MA (2004) Calmodulin-binding domains in Alzheimer's disease
proteins: extending the calcium hypothesis. Biochemical and Biophysical Research
Communications, 320, 1051-1054.
4.2 Enzyme binden Substrate und setzen sie zu Produkten um
Showalter AK & Tsai MD (2002) A reexamination of the nucleotide incorporation
fidelity of DNA polymerases. Biochemistry, 41, 10571-10576.Johnson KA (2008)
Role of induced fit in enzyme specificity: A molecular forward/reverse switch. Journal
of Biological Chemistry, 283, 26297-26301.
4.3 Liganden kommunizieren über allosterische Effekte
Ridge KD et al (2003) Phototransduction: crystal clear, Trends Biochem Sci 28, 479-
487
Villaverde A (2003) Allosteric enzymes as biosensors for molecular diagnosis. Febs
Letters, 554, 169-172.
Ascenzi P & Fasano M (2010) Allostery in a monomeric protein: The case of human
serum albumin. Biophysical Chemistry, 148, 16-22.
4.4 Die Bindung und Hydrolyse von Nucleotiden steuert Motorproteine
Tomkiewicz D, Nouwen N, & Driessen AJM (2007) Pushing, pulling and trapping -
Modes of motor protein supported protein translocation. Febs Letters, 581, 2820-
2828.
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Enernark EJ & Joshua-Tor L (2008) On helicases and other motor proteins. Current
Opinion in Structural Biology, 18, 243-257. (PDF)
4.5 Regulatorproteine werden oft über Phosphorylierung gesteuert
Johnson LN (2009) The regulation of protein phosphorylation. Biochemical Society
Transactions, 037, 627-641.
Bradshaw JM (2010) The Src, Syk, and Tec family kinases: Distinct types of
molecular switches. Cellular Signalling, 22, 1175-1184.
4.6 Enzyme passen sich metabolischen Bedürfnissen an
Roach PJ (2002) Glycogen and its metabolism, Curr Mol Med 2, 101-120
4.7 Proteine können auf mechanische Spannung reagieren
Tsunozaki M & Bautista DM (2009) Mammalian somatosensory
mechanotransduction. Current Opinion in Neurobiology, 19, 362-369.
Arnadottir J & Chalfie M (2010) Eukaryotic Mechanosensitive Channels. Annual
Review of Biophysics, Vol 39, 39, 111-137.
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5 Ebenen der Proteinarchitektur
5.1 Die Proteinstruktur ist hierarchisch gegliedert
Liu M, Grigoriev A (2004) Protein domains correlate strongly with exons in multiple
eukaryotic genomes - evidence of exon shuffling?, Trends Genet 20, 399-403
Thomas A, Joris B, & Brasseur R (2010) Standardized evaluation of protein stability.
Biochimica et Biophysica Acta-Proteins and Proteomics, 1804, 1265-1271.
5.2 Aminosäuren werden zu Polypeptidketten verknüpft
Tamura K, Alexander RW (2004) Peptide synthesis through evolution, Cell Mol Life
Sci 61, 1317-1330
Rohde H & Seitz O (2010) Ligation-Desulfurization: A Powerful Combination in the
Synthesis of Peptides and Glycopeptides. Biopolymers, 94, 551-559.
Belousoff MJ, Davidovich C, Zimmerman E, Caspi Y, Wekselman I, Rozenszajn L,
Shapira T, Sade-Falk O, Taha L, Bashan A, Weiss MS, & Yonath A (2010) Ancient
machinery embedded in the contemporary ribosome. Biochemical Society
Transactions, 38, 422-427.
5.3 Polypeptide können nach ihrer Synthese modifiziert werden
Jensen ON (2004) Modification-specific proteomics: characterization of post-
translational modifications by mass spectrometry, Curr Opin Chem Biol 8, 33-41
Freitas MA, Sklenar AR, & Parthun MR (2004) Application of mass spectrometry to
the identification and quantification of histone post-translational modifications.
Journal of Cellular Biochemistry, 92, 691-700. (PDF)
5.4 Planare Peptidbindungen bilden das Rückgrat der Proteine
Takahashi K, Uchida C, Shin RW, Shimazaki K, & Uchida T (2008) Prolyl isomerase,
Pin1: new findings of post-translational modifications and physiological substrates in
cancer, asthma and Alzheimer's disease. Cellular and Molecular Life Sciences, 65,
359-375.
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5.5 Die α-Helix ist ein prominentes Sekundärstrukturelement
Chiang D, Joshi AK, & Dill KA (2006) A grammatical theory for the conformational
changes of simple helix bundles. Journal of Computational Biology, 13, 21-42.
5.6 β-Faltblätter und β-Schleifen bilden ausgedehnte Sekundärstrukturen
Khakshoor O & Nowick JS (2008) Artificial beta-sheets: chemical models of beta-
sheets. Current Opinion in Chemical Biology, 12, 722-729. (PDF)
5.7 Sekundärstrukturelemente bilden wiederkehrende Motive
Watanabe M, Kobashigawa Y, Aizawa T, Demura M, & Nitta K (2004) A non-native
alpha-helix is formed in the beta-sheet region of the molten globule state of canine
milk lysozyme. Protein Journal, 23, 335-342.
5.8 Nichtkovalente Wechselwirkungen stabilisieren die Tertiärstruktur
Boas FE & Harbury PB (2007) Potential energy functions for protein design. Current
Opinion in Structural Biology, 17, 199-204.
5.9 Globuläre Proteine falten sich zu kompakten Strukturen
Frauenfelder H et al (2003) Myoglobin: the hydrogen atom of biology and a paradigm
of complexity, Proc Natl Acad Sci U S A 100, 8615-8617. (PDF)
Elber R (2010) Ligand diffusion in globins: simulations versus experiment. Current
Opinion in Structural Biology, 20, 162-167.
5.10 Mehrere Untereinheiten bilden die Quartärstruktur der Proteine
Brinda KV, Surolia A, & Vishveshwara S (2005) Insights into the quaternary
association of proteins through structure graphs: a case study of lectins. Biochemical
Journal, 391, 1-15. (PDF)
Rosenzweig R & Glickman MH (2008) Chaperone-driven proteasome assembly.
Biochemical Society Transactions, 36, 807-812.
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5.11 Proteine falten schrittweise in ihre native Konformation
Dobson CM (2003) Protein folding and misfolding, Nature 426, 884-890
Foguel B & Silva JL (2004) New insights into the mechanisms of protein misfolding
and aggregation in amyloidogenic diseases derived from pressure studies.
Biochemistry, 43, 11361-11370.
Ito K & Inaba K (2008) The disulfide bond formation (Dsb) system. Current Opinion in
Structural Biology, 18, 450-458.
Bandopadhyay R & de Belleroche J (2010) Pathogenesis of Parkinson's disease:
emerging role of molecular chaperones. Trends in Molecular Medicine, 16, 27-36.
5.12 Proteine können reversibel denaturieren
May BC et al (2004) Prions: so many fibers, so little infectivity, Trends Biochem Sci
29, 162-165
Oberhauser AF & Carrion-Vazquez M (2008) Mechanical biochemistry of proteins
one molecule at a time. Journal of Biological Chemistry, 283, 6617-6621. (PDF)
Perrin RJ, Fagan AM, & Holtzman DM (2009) Multimodal techniques for diagnosis
and prognosis of Alzheimer's disease. Nature, 461, 916-922.
5.13 Proteine können maßgeschneidert werden
Georlette D et al (2004) Some like it cold: biocatalysis at low temperatures, FEMS
Microbiol Rev 28, 25-42
Tian J & Xie ZJ (2008) The Na-K-ATPase and calcium-signaling microdomains.
Physiology, 23, 205-211. (PDF)
Wang HX, Nakata E, & Hamachi I (2009) Recent Progress in Strategies for the
Creation of Protein-Based Fluorescent Biosensors. Chembiochem, 10, 2560-2577.
Omenetto FG & Kaplan DL (2010) New Opportunities for an Ancient Material.
Science, 329, 528-531.
Cartellieri M, Bachmann M, Feldmann A, Bippes C, Stamova S, Wehner R, Temme
A, & Schmitz M (2010) Chimeric Antigen Receptor-Engineered T Cells for
Immunotherapy of Cancer. Journal of Biomedicine and Biotechnology. (PDF)
6 Proteine auf dem Prüfstand
6.1 Proteine müssen für die Aufreinigung in wässriger Lösung vorliegen
Bowie JU (2001) Stabilizing membrane proteins, Curr Opin Struct Biol 11, 397-402
Seddon AM, Curnow P, & Booth PJ (2004) Membrane proteins, lipids and
detergents: not just a soap opera. Biochimica et Biophysica Acta-Biomembranes,
1666, 105-117.
6.2 Die Gelfiltrationschromatographie trennt Proteine nach ihrer Größe
Winzor DJ (2003) The development of chromatography for the characterization of
protein interactions: a personal perspective, Biochem Soc Trans 31, 1010-1014
Berek D (2010) Size exclusion chromatography - A blessing and a curse of science
and technology of synthetic polymers. Journal of Separation Science, 33, 315-335.
6.3 Die Ionenaustauschchromatographie trennt Proteine unterschiedlicher Ladung
Stahlberg J (1999) Retention models for ions in chromatography, J Chromatogr A
855, 3-55
Jungbauer A & Hahn R (2009) Ion-Exchange Chromatography. Guide to Protein
Purification, Second Edition, 466, 349-371.
6.4 Die Affinitätschromatographie nutzt die spezifischen Bindungseigenschaften von Proteinen
Vikis HG, Guan KL (2004) Glutathione-S-transferase-fusion based assays for
studying protein-protein interactions, Methods Mol Biol 261, 175-86
Lee WC, Lee KH (2004) Applications of affinity chromatography in proteomics, Anal
Biochem 324, 1-10
Urh M, Simpson D, & Zhao K (2009) Affinity Chromatography: General Methods.
Guide to Protein Purification, Second Edition, 466, 417-438.
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6.5 Die Elektrophorese analysiert Proteingemische qualitativ
Kleparnik K & Bocek P (2010) Electrophoresis today and tomorrow: helping
biologists' dreams come true. Bioessays, 32, 218-226.
6.6 Die isoelektrische Fokussierung trennt Proteine nach Neutralpunkten
Van den Bergh G, Arckens L (2004) Fluorescent two-dimensional difference gel
electrophoresis unveils the potential of gel-based proteomics, Curr Opin Biotechnol
15, 38-43
Barnouin K (2004) Two-dimensional gel electrophoresis for analysis of protein
complexes, Methods Mol Biol 261, 479-98
Zilberstein G, Bukshpan S, & Righetti PG (2010) Third generation of focusing: Gel
matrices with immobilized cation gradients. Electrophoresis, 31, 1747-1753.
6.7 Antikörpersonden identifizieren Proteine
Shaw CE, Zheng J (1998) Western immunoblot analysis, Methods Mol Biol 105, 295-
306
Ahmed FE (2002) Detection of genetically modified organisms in foods, Trends
Biotechnol 20, 215-223
Kurien BT & Scofield RH (2009) A brief review of other notable protein detection
methods on blots. Methods Mol Biol, 536.
6.8 Enzymimmuntests quantifizieren Proteine in komplexen Gemischen
Plested JS et al (2003) ELISA, Methods Mol Med 71, 243-61
6.9 Die Fluoreszenzmikroskopie lokalisiert Proteine in Zellen
Huang B, Bates M, & Zhuang XW (2009) Super-Resolution Fluorescence
Microscopy. Annual Review of Biochemistry, 78, 993-1016. (PDF)
7 Die Erforschung der Proteinstruktur
7.1 Die Edman-Sequenzierung entziffert die Primärstruktur eines Proteins
Grant GA et al (1997) Edman sequencing as tool for characterization of synthetic
peptides, Methods Enzymol 289, 395-419
7.2 Die chemische Synthese von Peptiden erfolgt im Merrifield-Verfahren
Merrifield B (1997) Concept and early development of solid-phase peptide synthesis,
Methods Enzymol 289, 3-13
Marasco D, Perretta G, Sabatella M, & Ruvo M (2008) Past and Future Perspectives
of Synthetic Peptide Libraries. Current Protein & Peptide Science, 9, 447-467.
7.3 Die Massenspektrometrie bestimmt exakt Protein- und Peptidmassen
Steen H, Mann M (2004) The ABC's (and XYZ's) of peptide sequencing, Nat Rev Mol
Cell Biol 5, 699-711
Bergeron JJM, Au CE, Desjardins M, McPherson PS, & Nilsson T (2010) Cell biology
through proteomics - ad astra per alia porci. Trends in Cell Biology, 20, 337-345.
7.4 Die Röntgenstrukturanalyse entschlüsselt Proteinkonformationen
Torres J et al (2003) Membrane proteins: the 'Wild West' of structural biology, Trends
Biochem Sci 28, 137-144
Vrielink A, Sampson N (2003) Sub-Angstrom resolution enzyme X-ray structures: is
seeing believing?, Curr Opin Struct Biol 13, 709-715
Joachimiak A (2009) High-throughput crystallography for structural genomics.
Current Opinion in Structural Biology, 19, 573-584.
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7.5 Die Kernresonanzspektroskopie untersucht Proteine in Lösung
Baldwin AJ & Kay LE (2009) NMR spectroscopy brings invisible protein states into
focus. Nature Chemical Biology, 5, 808-814.
Sakurai K, Konuma T, Yagi M, & Goto Y (2009) Structural dynamics and folding of
beta-lactoglobulin probed by heteronuclear NMR. Biochimica et Biophysica Acta-
General Subjects, 1790, 527-537.
Jensen MR, Markwick PRL, Meier S, Griesinger C, Zweckstetter M, Grzesiek S,
Bernado P, & Blackledge M (2009) Quantitative Determination of the Conformational
Properties of Partially Folded and Intrinsically Disordered Proteins Using NMR
Dipolar Couplings. Structure, 17, 1169-1185.
8 Proteine als Strukturträger
8.1 Strukturproteine bilden die Matrix des Bindegewebes
Persikov AV, Ramshaw JA et al (2002) Peptide investigations of pairwise interactions
in the collagen triple-helix, J Mol Biol 316, 385-394
Brodsky B, Thiagarajan G, Madhan B, & Kar K (2008) Triple-helical peptides: An
approach to collagen conformation, stability, and self-association. Biopolymers, 89,
345-353.
Shoulders MD & Raines RT (2009) Collagen Structure and Stability. Annual Review
of Biochemistry, 78, 929-958. (PDF)
8.2 Posttranslationale Modifikationen stabilisieren die Tripelhelix
Olsen DR, Leigh SD et al (2001) Production of human type I collagen in yeast reveals
unexpected new insights into the molecular assembly of collagen trimers, J Biol
Chem 276, 24038-24043 (PDF)
Myllyharju J (2008) Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens
and regulation of the response to hypoxia, and their roles as treatment targets.
Annals of Medicine, 40, 402-417.
8.3 Chemische Quervernetzung stabilisiert die Kollagenfibrillen
Kagan HM, Li W (2003) Lysyl oxidase: properties, specificity, and biological roles
inside and outside of the cell, J Cell Biochem 88, 660-672
Robins SP (2007) Biochemistry and functional significance of collagen cross-linking.
Biochemical Society Transactions, 35, 849-852.
8.4 Störungen in der Kollagenbildung führen zu schwerwiegenden Erkrankungen
Mao JR, Bristow J (2001) The Ehlers-Danlos syndrome: on beyond collagens, J Clin
Invest 107, 1063-1069 (PDF)
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Gregersen N, Bolund L, & Bross P (2005) Protein misfolding, aggregation, and
degradation in disease. Molecular Biotechnology, 31, 141-150.
8.5 Elastin verleiht dem Bindegewebe Flexibilität
Tatham AS, Shewry PR (2000) Elastomeric proteins: biological roles, structures and
mechanisms, Trends Biochem Sci 25, 567-571
MacEwan SR & Chilkoti A (2010) Elastin-Like Polypeptides: Biomedical Applications
of Tunable Biopolymers. Biopolymers, 94, 60-77.
8.6 Proteoglykane und Glykosaminoglykane verleihen Widerstandsfähigkeit gegen Kompressionskräfte
Taylor KR & Gallo RL (2006) Glycosaminoglycans and their proteoglycans: host-
associated molecular patterns for initiation and modulation of inflammation. Faseb
Journal, 20, 9-22. (PDF)
Bishop JR, Schuksz M, & Esko JD (2007) Heparan sulphate proteoglycans fine-tune
mammalian physiology. Nature, 446, 1030-1037.
8.7 Adhäsionsproteine sind wichtige Komponenten der extrazellulären Matrix
Kaspar M, Zardi L, & Neri D (2006) Fibronectin as target for tumor therapy.
International Journal of Cancer, 118, 1331-1339.
Berrier AL & Yamada KM (2007) Cell-matrix adhesion. Journal of Cellular Physiology,
213, 565-573.
Rowe RG & Weiss SJ (2008) Breaching the basement membrane: who, when and
how? Trends in Cell Biology, 18, 560-574.
9 Proteine als molekulare Motoren
9.1 Skelettmuskelfasern enthalten geordnete Bündel aus Proteinfilamenten
Granzier H & Labeit S (2002) Cardiac titin: an adjustable multi-functional spring.
Journal of Physiology-London, 541, 335-342. (PDF)
Kim J, Lowe T, & Hoppe T (2008) Protein quality control gets muscle into shape.
Trends in Cell Biology, 18, 264-272.
9.2 Dicke und dünne Filamente gleiten bei der Kontraktion aneinander vorbei
Volkmann N, Hanein D (2000) Actomyosin: law and order in motility, Curr Opin Cell
Biol 12, 26-34
Gordon AM, Homsher E, & Regnier M (2000) Regulation of contraction in striated
muscle. Physiological Reviews, 80, 853-924. (PDF)
9.3 Myosinköpfe binden und hydrolysieren ATP
Kolomeisky AB & Fisher ME (2007) Molecular motors: A theorist's perspective.
Annual Review of Physical Chemistry, 58, 675-695.
Spudich JA & Sivaramakrishnan S (2010) Myosin VI: an innovative motor that
challenged the swinging lever arm hypothesis. Nature Reviews Molecular Cell
Biology, 11, 128-137. (PDF)
9.4 Die Struktur des Myosinkopfs ist im atomaren Detail bekannt
Cooke R (1999) Myosin structure: does the tail wag the dog?, Curr Biol 9, R773-
R775
Sweeney HL & Houdusse A (2010) Myosin VI Rewrites the Rules for Myosin Motors.
Cell, 141, 573-582.
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9.5 Ein elektrischer Reiz löst die Muskelkontraktion aus
Michele DE, Metzger JM (2000) Physiological consequences of tropomyosin
mutations associated with cardiac and skeletal myopathies, J Mol Med 78, 543-553
Kobayashi T & Solaro RJ (2005) Calcium, thin filaments, and the integrative biology
of cardiac contractility. Annual Review of Physiology, 67, 39-67.
9.6 Glatte Muskulatur kontrahiert nach reversibler Phosphorylierung von Myosin
Wang CL (2001) Caldesmon and smooth-muscle regulation, Cell Biochem Biophys
35, 275-288
Murthy KS (2006) Signaling for contraction and relaxation in smooth muscle of the
gut. Annual Review of Physiology, 68, 345-374.
9.7 Die Duchenne-Muskeldystrophie beruht auf einem Defekt im Dystrophingen
Cossu G & Sampaolesi M (2007) New therapies for Duchenne muscular dystrophy:
challenges, prospects and clinical trials. Trends in Molecular Medicine, 13, 520-526.
Woolner S & Bement WM (2009) Unconventional myosins acting unconventionally.
Trends in Cell Biology, 19, 245-252.
10 Dynamik sauerstoffbindender Proteine
10.1 Myoglobin bindet Sauerstoff mittels seiner prosthetischen Gruppe
Brunori M (2001) Nitric oxide moves myogobin to center stage, Trends Biochem Sci
26, 209-210
Wittenberg JB & Wittenberg BA (2003) Myoglobin function reassessed. Journal of
Experimental Biology, 206, 2011-2020. (PDF)
10.2 Die Sauerstoffdissoziationskurve von Myoglobin ist hyperbolisch
Garry D et al (1998) Mice without myoglobin, Nature 395, 905-908
Gros G, Wittenberg BA, & Jue T (2010) Myoglobin's old and new clothes: from
molecular structure to function in living cells. Journal of Experimental Biology, 213,
2713-2725.
10.3 Hämoglobin ist ein tetrameres Protein
Kundu S et al (2003) Plants, humans and hemoglobins, Trends Plant Sci 8, 387-393
Lukin JA, Ho C (2004) The structure - function relationship of hemoglobin in solution
at atomic resolution, Chem Rev 104, 1219-1230
10.4 Die Sauerstoffbindung von Hämoglobin ist kooperativ
Manning JM et al (1999) Remote contributions to subunit interactions: lessons from
adult and fetal hemoglobins, Trends Biochem Sci 24, 211-212
Ackers GK & Holt JM (2006) Asymmetric cooperativity in a symmetric tetramer:
Human hemoglobin. Journal of Biological Chemistry, 281, 11441-11443. (PDF)
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10.5 Oxy- und Desoxyhämoglobin unterscheiden sich in ihrer Raumstruktur
Verde C, Vergara A, Mazzarella L, & di Prisco G (2008) The Hemoglobins of Fishes
Living at Polar Latitudes - Current Knowledge on Structural Adaptations in a
Changing Environment. Current Protein & Peptide Science, 9, 578-590.
Bellelli A (2010) Hemoglobin and Cooperativity: Experiments and Theories. Current
Protein & Peptide Science, 11, 2-36.
10.6 Zwei unterschiedliche Modelle beschreiben kooperatives Verhalten
Royer WE, Knapp JE, Strand K, & Heaslet HA (2001) Cooperative hemoglobins:
conserved fold, diverse quaternary assemblies and allosteric mechanisms. Trends in
Biochemical Sciences, 26, 297-304.
Shikama K (2006) Nature of the FeO2 bonding in myoglobin and hemoglobin: A new
molecular paradigm. Progress in Biophysics & Molecular Biology, 91, 83-162.
10.7 2,3-Bisphosphoglycerat bindet in der zentralen Pore des Hämoglobins
Yachie-Kinoshita A, Nishino T, Shimo H, Suematsu M, & Tomita M (2010) A
Metabolic Model of Human Erythrocytes: Practical Application of the E-Cell
Simulation Environment. Journal of Biomedicine and Biotechnology. (PDF)
10.8 Protonierung von Hämoglobin erleichtert die O2-Abgabe in den
Kapillaren
Lane P, Gross S (2002) Hemoglobin as a chariot for NO bioactivity, Nat Med 8, 657-
658
Gladwin MT et al (2003) Nitric oxide's reactions with hemoglobin: a view through the
SNO-storm, Nat Med 9, 496-500
Giardina B, Mosca D, & De Rosa MC (2004) The Bohr effect of haemoglobin in
vertebrates: an example of molecular adaptation to different physiological
requirements. Acta Physiologica Scandinavica, 182, 229-244.
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10.9 Hämoglobinopathien beruhen auf molekularen Defekten von Hämoglobin
Strasser BJ (1999) Sickle cell anemia, a molecular disease, Science 286, 1488-1490
Allison AC (2002) The discovery of resistance to malaria of sickle-cell heterozygotes,
Biochem Mol Biol Educ 30, 279-287 (PDF)
Smiley D, Dagogo-Jack S, & Umpierrez G (2008) Therapy Insight: metabolic and
endocrine disorders in sickle cell disease. Nature Clinical Practice Endocrinology &
Metabolism, 4, 102-109.
10.10 Eisen wird mithilfe von Proteinen resorbiert, transportiert und gespeichert
Aisen P et al (1999) Iron metabolism, Curr Opin Chem Biol 3, 200-206
Dunn LL, Rahmanto YS, & Richardson DR (2007) Iron uptake and metabolism in the
new millennium. Trends in Cell Biology, 17, 93-100.
Roy CN, Enns CA (2000) Iron homeostasis: new tales from the crypt, Blood 96,
4020-4027 (PDF)
11 Proteine als molekulare Katalysatoren
11.1 Enzyme haben eine hohe Substrat- und Reaktionsspezifität
Mesecar A & Koshland D (2000) A new model for protein stereospecificity, Nature
403, 614-615
Copley SD (2003) Enzymes with extra talents: moonlighting functions and catalytic
promiscuity, Curr Opin Chem Biol 7, 265-272
Siddiqui KS & Cavicchioli R (2006) Cold-adapted enzymes. Annual Review of
Biochemistry, 75, 403-433.
11.2 Das aktive Zentrum wird von reaktiven Aminosäuren gebildet
Wolfe MS, Kopan R (2004) Intramembrane proteolysis: theme and variations,
Science 305, 1119-1123
Eliot AC, Kirsch JF (2004) Pyridoxal phosphate enzymes: mechanistic, structural,
and evolutionary considerations, Annu Rev Biochem 73, 383-415
Berger F et al (2004) The new life of a centenarian: signalling functions of NAD(P),
Trends Biochem Sci 29, 111-118
Khersonsky O, Roodveldt C, & Tawfik DS (2006) Enzyme promiscuity: evolutionary
and mechanistic aspects. Current Opinion in Chemical Biology, 10, 498-508.
11.3 Enzyme werden nach Art der katalysierten Reaktion klassifiziert
Hult K & Berglund P (2007) Enzyme promiscuity: mechanism and applications.
Trends in Biotechnology, 25, 231-238.
11.4 Der Übergangszustand liegt zwischen Edukt und Produkt einer Reaktion
Warshel A, Sharma PK, Kato M, Xiang Y, Liu HB, & Olsson MHM (2006) Electrostatic
basis for enzyme catalysis. Chemical Reviews, 106, 3210-3235.
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11.5 Enzyme setzen die freie Aktivierungsenergie von Reaktionen herab
Stroppolo ME et al (2001) Superefficient enzymes, Cell Mol Life Sci 58, 1451-1460
Garcia-Viloca M et al (2004) How enzymes work: analysis by modern rate theory and
computer simulations, Science 303, 186-195
Hu H & Yang WT (2008) Free energies of chemical reactions in solution and in
enzymes with ab initio quantum mechanics/molecular mechanics methods. Annual
Review of Physical Chemistry, 59, 573-601.
12 Mechanismen der Katalyse
12.1 Enzyme nutzen unterschiedliche Katalysestrategien
Kraut DA et al (2003) Challenges in enzyme mechanism and energetics, Annu Rev
Biochem 72, 517-71
Evans MJ & Cravatt BF (2006) Mechanism-based profiling of enzyme families.
Chemical Reviews, 106, 3279-3301.
12.2 Enzyme binden bevorzugt den Übergangszustand
Borden J, Crans DC, & Florian J (2006) Transition state analogues for nucleotidyl
transfer reactions: Structure and stability of pentavalent vanadate and phosphate
ester dianions. Journal of Physical Chemistry B, 110, 14988-14999.
Senn HM & Thiel W (2007) QM/MM studies of enzymes. Current Opinion in Chemical
Biology, 11, 182-187.
Wojcik T & Kiec-Kononowicz K (2008) Catalytic activity of certain antibodies as a
potential tool for drug synthesis and for directed prodrug therapies. Current Medicinal
Chemistry, 15, 1606-1615.
12.3 Lactat-Dehydrogenase verschließt nach Substratbindung das aktive Zentrum
Gutteridge A, Thornton J (2004) Conformational change in substrate binding,
catalysis and product release: an open and shut case?, FEBS Lett 567, 67-73
Zhou SF, Zhou ZW, Yang LP, & Cai JP (2009) Substrates, Inducers, Inhibitors and
Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in
Drug Development. Current Medicinal Chemistry, 16, 3480-3675.
12.4 Die katalytische Triade ist das Herzstück im aktiven Zentrum von Trypsin
Blow D (1997) The tortuous story of Asp...His...Ser: Structural analysis of
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20
Hedstrom L (2002) Serine protease mechanism and specificity, Chem Rev 102,
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12.5 Trypsin bildet eine kovalentes Acyl-Intermediat
Wilmouth R et al (2001) X-Ray snapshots of serine protease catalysis reveals a
tetrahedral intermediate, Nature Struct Biol 8, 689-694
Dunn BM & Uversky VN (2009) Cryoenzymology: Enzyme Action in Slow Motion.
Current Protein & Peptide Science, 10, 408-415.
12.6 Proteasen haben vielfältige biologische Aufgaben
De Clercq E (2007) The design of drugs for HIV and HCV. Nature Reviews Drug
Discovery, 6, 1001-1018.
Page MJ & Di Cera E (2008) Serine peptidases: Classification, structure and
function. Cellular and Molecular Life Sciences, 65, 1220-1236.
12.7 Ribozyme sind katalytisch aktive Ribonucleinsäuren
Lilley DM (2003) The origins of RNA catalysis in ribozymes, Trends Biochem Sci 28,
495-501
Isaacs FJ, Dwyer DJ, & Collins JJ (2006) RNA synthetic biology. Nature
Biotechnology, 24, 545-554.
Serganov A & Patel DJ (2007) Ribozymes, riboswitches and beyond: regulation of
gene expression without proteins. Nature Reviews Genetics, 8, 776-790.
21
13 Regulation der Enzymaktivität
13.1 Geschwindigkeitskonstanten charakterisieren chemische Reaktionen
Kraut DA, Carroll KS, & Herschlag D (2003) Challenges in enzyme mechanism and
energetics. Annual Review of Biochemistry, 72, 517-571.
Walde S & Kehlenbach RH (2010) The Part and the Whole: functions of nucleoporins
in nucleocytoplasmic transport. Trends in Cell Biology, 20, 461-469.
13.2 Die Michaelis-Menten-Gleichung beschreibt eine einfache Enzymkinetik
Xie XS, Lu HP (1999) Single-molecule enzymology, J Biol Chem 274, 15967-70
(PDF)
Atkins WM (2005) Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed
reactions. Annual Review of Pharmacology and Toxicology, 45, 291-310.
Moffitt JR, Chemla YR, & Bustamante C (2010) Methods in Statistical Kinetics.
Elsevier Academic Press Inc., San Diego.
13.3 Michaelis-Konstante und Wechselzahl sind wichtige Kenngrößen von Enzymen
Fox RJ & Clay MD (2009) Catalytic effectiveness, a measure of enzyme proficiency
for industrial applications. Trends in Biotechnology, 27, 137-140.
13.4 Die Enzymkinetik hilft bei der Untersuchung von Enzymmechanismen
Peracchi A (2001) Enzyme catalysis: removing chemically 'essential' residues by site-
directed mutagenesis, Trends Biochem Sci 26, 497-503
Cleland WW (2005) The use of isotope effects to determine enzyme mechanisms.
Archives of Biochemistry and Biophysics, 433, 2-12.
22
13.5 Kompetitive Inhibitoren binden an das aktive Zentrum und verhindern den Substratzutritt
Istvan ES, Deisenhofer J (2001) Structural mechanism for statin inhibition of HMG-
CoA reductase, Science 292, 1160-1164
Simmons DL et al (2004) Cyclooxygenase isozymes: the biology of prostaglandin
synthesis and inhibition, Pharmacol Rev 56, 387-437
Tafi A, Angeli L, Venturini G, Travagli M, Corelli F, & Botta M (2006) Computational
studies of competitive inhibitors of nitric oxide synthase (NOS) enzymes: Towards the
development of powerful and isoform selective inhibitors. Current Medicinal
Chemistry, 13, 1929-1946.
13.6 Hohe Substratkonzentrationen heben die kompetitive Inhibition auf
Schep LJ, Slaughter RJ, Temple WA, & Beasley DMG (2009) Diethylene glycol
poisoning. Clinical Toxicology, 47, 525-535.
13.7 Kovalent bindende Inhibitoren hemmen irreversibel
Nitiss JL (2009) Targeting DNA topoisomerase II in cancer chemotherapy. Nature
Reviews Cancer, 9, 338-350. (PDF)
Singh J, Petter RC, & Kluge AF (2010) Targeted covalent drugs of the kinase family.
Current Opinion in Chemical Biology, 14, 475-480.
13.8 Allosterische Regulatoren modulieren die Enzymaktivität
Dijkstra BW, Matthews RG (2003) Catalysis and regulation - from structure to
function, Curr Opin Struct Biol 13, 706-708
Goodey NM & Benkovic SJ (2008) Allosteric regulation and catalysis emerge via a
common route. Nature Chemical Biology, 4, 474-482.
13.9 Heterotrope Effektoren binden an regulatorische Untereinheiten
Lim WA (2002) The modular logic of signaling proteins: building allosteric switches
from simple binding domains, Curr Opin Struct Biol 12, 61-68
23
24
Villaverde A (2003) Allosteric enzymes as biosensors for molecular diagnosis, FEBS
Lett 554, 169-172
Gold MG, Barford D, & Komander D (2006) Lining the pockets of kinases and
phosphatases. Current Opinion in Structural Biology, 16, 693-701.
13.10 Reversible Phosphorylierung reguliert die Enzymaktivität
Kolmodin K, Aqvist J (2001) The catalytic mechanism of protein tyrosine
phosphatases revisited, FEBS Lett 498, 208-213
Hirose Y & Ohkuma Y (2007) Phosphorylation of the c-terminal domain of RNA
polymerase II plays central roles in the integrated events of eucaryotic gene
expression. Journal of Biochemistry, 141, 601-608.
Pulido R & Hooft van Huijsduijnen R (2008) Protein tyrosine phosphatases: dual-
specificity phosphatases in health and disease. Febs Journal, 275, 848-866.
13.11 Gezielte proteolytische Spaltungen können Zymogene aktivieren
Krem MM, Di Cera E (2002) Evolution of enzyme cascades from embryonic
development to blood coagulation, Trends Biochem Sci 27, 67-74
Amour A et al (2004) General considerations for proteolytic cascades, Biochem Soc
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Regulation. Journal of Biological Chemistry, 284, 21777-21781. (PDF)
14 Enzymkaskaden des Bluts
14.1 Proteolytische Kaskaden steuern die Bildung und Auflösung von Blutgerinnseln
Davidson CJ et al (2003) 450 million years of hemostasis, J Thromb Haemost 1,
1487-1494
Schenone M et al (2004) The blood coagulation cascade, Curr Opin Hematol 11,
272-277
Monroe DM & Hoffman M (2006) What does it take to make the perfect clot?
Arteriosclerosis Thrombosis and Vascular Biology, 26, 41-48. (PDF)
14.2 Die Initiation der Gerinnungskaskade erfolgt über den Gewebsfaktor
McVey JH (2003) Your bleeding heart: lessons from low tissue factor expression in
mice, Trends Pharmacol Sci 24, 269-272
Hoffman M (2003) A cell-based model of coagulation and the role of factor VIIa,
Blood Rev 17, S1-5
Mann KG, Kalafatis M (2003) Factor V: a combination of Dr Jekyll and Mr Hyde,
Blood 101, 20-30 (PDF)
Persson E, Bolt G, Steenstrup TD, & Ezban M (2010) Recombinant coagulation
factor VIIa - from molecular to clinical aspects of a versatile haemostatic agent.
Thrombosis Research, 125, 483-489.
14.3 Fibrinmonomere assoziieren zu einem Netzwerk
Yang Z, Mochalkin I et al (2000) Crystal structure of native chicken fibrinogen at 5.5-
A resolution, Proc Natl Acad Sci U S A 97, 3907-3912 (PDF)
Doolittle RF (2003) Structural basis of the fibrinogen-fibrin transformation:
contributions from X-ray crystallography, Blood Rev 17, 33-41
Guthold M, Liu W, Sparks EA, Jawerth LM, Peng L, Falvo M, Superfine R, Hantgan
RR, & Lord ST (2007) A comparison of the mechanical and structural properties of
fibrin fibers with other protein fibers. Cell Biochemistry and Biophysics, 49, 165-181.
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14.4 Gerinnungsfaktoren besitzen einen modularen Aufbau
Furie B et al (1999) Vitamin K-dependent biosynthesis of gamma-carboxyglutamic
acid, Blood 93, 1798-1808 (PDF)
Lee CJ, Chandrasekaran V, Wu SW, Duke RE, & Pedersen LG (2010) Recent
Estimates of the Structure of the Factor VIIa (FVIIa)/Tissue Factor (TF) and Factor
Xa (FXa) Ternary Complex. Thrombosis Research, 125, S7-S10.
14.5 Inhibition und Proteolyse kontrollieren die Blutgerinnung
Huntington JA, Baglin TP (2003) Targeting thrombin - rational drug design from
natural mechanisms, Trends Pharmacol Sci 24, 589-595
Bussey H, Francis JL (2004) Heparin overview and issues, Pharmacotherapy 24,
103S-107S
Lwaleed BA & Bass PS (2006) Tissue factor pathway inhibitor: structure, biology and
involvement in disease. Journal of Pathology, 208, 327-339.
14.6 Das fibrinolytische System löst Thromben auf
Medved L, Nieuwenhuizen W (2003) Molecular mechanisms of initiation of fibrinolysis
by fibrin, Thromb Haemost 89, 409-419
Laurens N, Koolwijk P, & De Maat MPM (2006) Fibrin structure and wound healing.
Journal of Thrombosis and Haemostasis, 4, 932-939.
Zorio E, Gilabert-Estelles J, Espana F, Ramon LA, Cosin R, & Estelles A (2008)
Fibrinolysis: The key to new pathogenetic mechanisms. Current Medicinal Chemistry,
15, 923-929.
14.7 Defekte Gerinnungsfaktoren führen zur Hämophilie
Bolton-Maggs PH, Pasi KJ (2003) Haemophilias A and B, Lancet 361, 1801-1809
Nathwani AC et al (2004) Prospects for gene therapy of haemophilia, Haemophilia
10, 309-318
O'Connor TP & Crystal RG (2006) Genetic medicines: treatment strategies for
hereditary disorders. Nature Reviews Genetics, 7, 261-276.
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27
Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL,
Rick ME, Sadler JE, Weinstein M, & Yawn BP (2008) von Willebrand disease (VWD):
evidence-based diagnosis and management guidelines, the National Heart, Lung,
and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia, 14, 171-232.
15 Evolution der Proteine
15.1 Mutationen und Duplikationen treiben die Proteinevolution an
Kinch LN, Grishin NV (2002) Evolution of protein structures and functions, Curr Opin
Struct Biol 12, 400-408
Kondrashov FA & Kondrashov AS (2006) Role of selection in fixation of gene
duplications. Journal of Theoretical Biology, 239, 141-151.
Conant GC & Wolfe KH (2008) Turning a hobby into a job: How duplicated genes find
new functions. Nature Reviews Genetics, 9, 938-950.
Soskine M & Tawfik DS (2010) Mutational effects and the evolution of new protein
functions. Nature Reviews Genetics, 11, 572-582.
15.2 Domänen sind die Bausteine der Proteinevolution
Khosla C, Harbury PB (2001) Modular enzymes, Nature 409, 247-252
Kolkman JA, Stemmer WP (2001) Directed evolution of proteins by exon shuffling,
Nat Biotechnol 19, 423-428
Bhattacharyya RP, Remenyi A, Yeh BJ, & Lim WA (2006) Domains, motifs, and
scaffolds: The role of modular interactions in the evolution and wiring of cell signaling
circuits. Annual Review of Biochemistry, 75, 655-680.
Han JH, Batey S, Nickson AA, Teichmann SA, & Clarke J (2007) The folding and
evolution of multidomain proteins. Nature Reviews Molecular Cell Biology, 8, 319-
330.
15.3 Sequenzvergleiche spüren Schlüsselpositionen in verwandten Proteinen auf
Jeanmougin F et al (1998) Multiple sequence alignment with Clustal X, Trends
Biochem Sci 23, 403-405
Kumar S & Filipski A (2007) Multiple sequence alignment: In pursuit of homologous
DNA positions. Genome Research, 17, 127-135. (PDF)
Lenaerts T, Schymkowitz J, & Rousseau F (2009) Protein Domains as Information
Processing Units. Current Protein & Peptide Science, 10, 133-145.
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15.4 Der Vergleich von Tertiärstrukturen verrät entfernte Verwandtschaften
Hocker B et al (2002) A common evolutionary origin of two elementary enzyme folds,
FEBS Lett 510, 133-135
Lee D et al (2003) A structural perspective on genome evolution, Curr Opin Struct
Biol 13, 359-369
Carugo O (2007) Recent progress in measuring structural similarity between
proteins. Current Protein & Peptide Science, 8, 219-241.
15.5 Proteine werden in Datenbanken gesammelt
Orengo CA et al (2001) Review: what can structural classifications reveal about
protein evolution?, J Struct Biol 134, 145-165
Koonin EV et al (2002) The structure of the protein universe and genome evolution,
Nature 420, 218-223
Shen MY & Sali A (2006) Statistical potential for assessment and prediction of protein
structures. Protein Science, 15, 2507-2524. (PDF)
Dunbrack RL (2006) Sequence comparison and protein structure prediction. Current
Opinion in Structural Biology, 16, 374-384.
Raman P, Cherezov V, & Caffrey M (2006) The membrane protein data bank.
Cellular and Molecular Life Sciences, 63, 36-51. (PDF)
15.6 Die Zahl der Proteine ist sehr viel größer als die der Gene
Burley SK, Bonanno JB (2002) Structural genomics of proteins from conserved
biochemical pathways and processes, Curr Opin Struct Biol 12, 383-391
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126, 37-47.
Jensen ON (2006) Interpreting the protein language using proteomics. Nature
Reviews Molecular Cell Biology, 7, 391-403.
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Teil III Speicherung und Ausprägung von Erbinformation
16 Nucleinsäuren – Struktur und Organisation
16.1 Aufbau der DNA
Burge S, Parkinson GN, Hazel P, Todd AK, & Neidle S (2006) Quadruplex DNA:
sequence, topology and structure. Nucleic Acids Research, 34, 5402-5415. (PDF)
16.2 Antiparallele DNA-Stränge bilden eine Doppelhelix
Watson JD, Crick FHC (1953) Molecular structure of nucleic acids, Nature 171, 737-
738 (PDF)
Andersen ES (2010) Prediction and design of DNA and RNA structures. New
Biotechnology, 27, 184-193.
16.3 Die Asymmetrie der Basenpaare erzeugt kleine und große Furchen
Dickerson RE et al (1982) The anatomy of A-, B- and Z-DNA, Science 216, 475-485
Herbert A, Rich A (1996) The biology of lefthanded Z-DNA, J Biol Chem 271, 11595-
598 (PDF)
Mooers BH (2009) Crystallographic studies of DNA and RNA. Methods, 47, 168-176.
Masquida B, Beckert B, & Jossinet F (2010) Exploring RNA structure by integrative
molecular modelling. New Biotechnology, 27, 170-183.
16.4 Chromosomen sind Komplexe aus DNA und Histonen
Luger K et al (1997) Crystal structure of the nucleosome core particle at 2.8 Å
resolution, Nature 389, 251-260
Shilatifard A (2006) Chromatin modifications by methylation and ubiquitination:
Implications in the regulation of gene expression. Annual Review of Biochemistry, 75,
243-269.
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31
Li B, Carey M, & Workman JL (2007) The role of chromatin during transcription. Cell,
128, 707-719.
Taverna SD, Li H, Ruthenburg AJ, Allis CD, & Patel DJ (2007) How chromatin-
binding modules interpret histone modifications: lessons from professional pocket
pickers. Nature Structural & Molecular Biology, 14, 1025-1040.
16.5 Nucleosomen bilden die Glieder einer Chromatinkette
Hirano T (2006) At the heart of the chromosome: SMC proteins in action. Nature
Reviews Molecular Cell Biology, 7, 311-322.
Bailey SM & Murnane JP (2006) Telomeres, chromosome instability and cancer.
Nucleic Acids Research, 34, 2408-2417. (PDF)
Bazile F, St-Pierre J, & D'Amours D (2010) Three-step model for condensin
activation during mitotic chromosome condensation. Cell Cycle, 9, 3243-3255.
(Website)
16.6 Das Genom von E. coli ist ringförmig
Blattner FR et al (1997) The complete genome sequence of Escherichia coli K-12,
Science 277, 1453-62
Espeli O & Boccard F (2006) Organization of the Escherichia coli chromosome into
macrodomains and its possible functional implications. Journal of Structural Biology,
156, 304-310.
17 Transkription – Umschrift genetischer Information
17.1 Ribonucleinsäuren sind Produkte der Transkription
Orphanides G, Reinberg D (2002) A unified theory of gene expression, Cell 108, 439-
451
White RJ & Sharrocks AD (2010) Coordinated control of the gene expression
machinery. Trends in Genetics, 26, 214-220.
17.2 Die Transkription startet an der Promotorregion
Hahn S (2004) Structure and mechanism of the RNA polymerase II transcription
machinery, Nat Struct Mol Biol 11, 394-403 (PDF)
Haugen SP, Ross W, & Gourse RL (2008) Advances in bacterial promoter
recognition and its control by factors that do not bind DNA. Nature Reviews
Microbiology, 6, 507-519.
17.3 RNA-Polymerase windet den Doppelstrang auf
Woychik NA, Hampsey M (2002) The RNA polymerase II machinery: structure,
illuminates function, Cell 108, 453-463
Kornberg RD (2007) The molecular basis of eucaryotic transcription. Cell Death and
Differentiation, 14, 1989-1997. (PDF)
17.4 Eukaroytische Zellen besitzen drei nucleäre RNA-Polymerasen
Cramer P, Armache KJ, Baumli S, Benkert S, Brueckner E, Buchen C, Damsma GE,
Dengl S, Geiger SR, Jaslak AJ, Jawhari A, Jennebach S, Kamenski T, Kettenberger
H, Kuhn CD, Lehmann E, Leike K, Sydow JE, & Vannini A (2008) Structure of
eukaryotic RNA polymerases. Annual Review of Biophysics, 37, 337-352.
Geiduschek EP (2009) Without a License, or Accidents Waiting to Happen. Annual
Review of Biochemistry, 78, 1-28.
Selth LA, Sigurdsson S, & Svejstrup JQ (2010) Transcript Elongation by RNA
Polymerase II. ANNUAL REVIEWS, PALO ALTO.
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17.5 Eukaryotische RNA macht eine Reifung durch
Proudfoot NJ et al (2002) Integrating mRNA processing with transcription, Cell 108,
501-512
Shyu AB, Wilkinson MF, & van Hoof A (2008) Messenger RNA regulation: to
translate or to degrade. Embo Journal, 27, 471-481. (PDF)
17.6 Der Spleißvorgang entfernt Introns aus unreifer RNA
Roy SW & Gilbert W (2006) The evolution of spliceosomal introns: patterns, puzzles
and progress. Nature Reviews Genetics, 7, 211-221.
Wang GS & Cooper TA (2007) Splicing in disease: disruption of the splicing code and
the decoding machinery. Nature Reviews Genetics, 8, 749-761.
Wang GS & Cooper TA (2007) Splicing in disease: disruption of the splicing code and
the decoding machinery. Nature Reviews Genetics, 8, 749-761.
17.7 Das Spleißosom ist ein multikatalytischer Komplex
Murray HL, Jarrell KA (1999) Flipping the switch to an active spliceosome, Cell 96,
599-602
Stahley MR & Strobel SA (2006) RNA splicing: group I intron crystal structures reveal
the basis of splice site selection and metal ion catalysis. Current Opinion in Structural
Biology, 16, 319-326.
17.8 Alternatives Spleißen und RNA-Editing erhöhen die strukturelle Variabilität
Gott JM, Emeson RB (2000) Functions and mechanisms of RNA editing, Annu Rev
Genet 34, 499-531
Blencowe BJ (2006) Alternative splicing: New insights from global analyses. Cell,
126, 37-47.
Xing Y & Lee C (2006) Alternative splicing and RNA selection pressure - evolutionary
consequences for eukaryotic genomes. Nature Reviews Genetics, 7, 499-509.
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17.9 RNA-Polymerase I produziert ribosomale RNA
Scheer U, Hock R (1999) Structure and function of the nucleolus, Curr Opin Cell Biol
11, 385-390
Haeusler RA & Engelke DR (2006) Spatial organization of transcription by RNA
polymerase III. Nucleic Acids Research, 34, 4826-4836. (PDF)
Boisvert FM, van Koningsbruggen S, Navascues J, & Lamond AI (2007) The
multifunctional nucleolus. Nature Reviews Molecular Cell Biology, 8, 574-585.
17.10 Transfer-RNAs werden posttranskriptional modifiziert
Kirsebohm LA (2002) RNase P RNA-mediated catalysis, Biochem Soc Trans 30,
1153-58
Kazantsev AV & Pace NR (2006) Bacterial RNase P: a new view of an ancient
enzyme. Nature Reviews Microbiology, 4, 729-740.
Agris PF, Vendeix FAP, & Graham WD (2007) tRNA's wobble decoding of the
genome: 40 years of modification. Journal of Molecular Biology, 366, 1-13.
Gustilo EM, Franck APF, & Agris PF (2008) tRNA's modifications bring order to gene
expression. Current Opinion in Microbiology, 11, 134-140. (PDF)
18 Translation – Decodierung genetischer Information
18.1 Basentripletts sind genetische Informationseinheiten
Kapp LD, Lorsch JR (2004) The Molecular Mechanisms of Eucarytic Translation,
Annu Rev Biochem 73, 657-704
Koonin EV & Novozhilov AS (2009) Origin and Evolution of the Genetic Code: The
Universal Enigma. Iubmb Life, 61, 99-111.
18.2 Transfer-Ribonucleinsäuren haben eine bipolare Struktur
Ogle JM et al (2003) Insights into the decoding mechanism from recent ribosome
structures, Trends Biochem Sci 28, 259-265
Park SG, Schimmel P, & Kim S (2008) Aminoacyl tRNA synthetases and their
connections to disease. Proceedings of the National Academy of Sciences of the
United States of America, 105, 11043-11049. (PDF)
Guo M, Yang XL, & Schimmel P (2010) New functions of aminoacyl-tRNA
synthetases beyond translation. Nature Reviews Molecular Cell Biology, 11, 668-674.
18.3 Ribosomen dienen bei der Translation als Werkbänke
Yusupov M et al (2001) Crystal structure of the ribosome at 5.5 Å resolution, Science
292, 883-896
Beringer M & Rodnina MV (2007) The ribosomal peptidyl transferase. Molecular Cell,
26, 311-321.
Steitz TA (2008) A structural understanding of the dynamic ribosome machine.
Nature Reviews Molecular Cell Biology, 9, 242-253.
Schmeing TM & Ramakrishnan V (2009) What recent ribosome structures have
revealed about the mechanism of translation. Nature, 461, 1234-1242.
18.4 Initiationsfaktoren steuern die Startphase der Translation
Proud CG (2007) Signalling to translation: how signal transduction pathways control
the protein synthetic machinery. Biochemical Journal, 403, 217-234.
35
Hinnebusch AG (2006) eIF3: a versatile scaffold for translation initiation complexes.
Trends in Biochemical Sciences, 31, 553-562.
Kolitz SE & Lorsch JR (2010) Eukaryotic initiator tRNA: Finely tuned and ready for
action. Febs Letters, 584, 396-404.
18.5 Molekulare Roboter assemblieren die Polypeptidkette
Crick FHC (1966) Codon-anticodon pairing: the wobble hypothesis, J Mol Biol 19,
548-555
Andersen GR, et al (2003) Elongation factors in protein biosynthesis, Trends
Biochem Sci 28, 434-441
Abbott CM, Proud CG (2004) Translation factors, in sickness and in health, Trends
Biochem Sci 29, 25-31
Peterlin BM & Price DH (2006) Controlling the elongation phase of transcription with
P-TEFb. Molecular Cell, 23, 297-305.
Mateyak MK & Kinzy TG (2010) eEF1A: Thinking Outside the Ribosome. Journal of
Biological Chemistry, 285, 21209-21213.
18.6 Die Proteinbiosynthese ist ein ökonomischer Prozess
Rodnina MV, Wintermeyer W (2001) Ribosome fidelity, tRNA discrimination,
proofreading and induced fit, Trends Biochem Sci 26, 124-130
Zaher HS & Green R (2009) Fidelity at the Molecular Level: Lessons from Protein
Synthesis. Cell, 136, 746-762.
18.7 Die Translation wird effizient kontrolliert
Kimball SR (1999) Eukaryotic initiation factor eIF2, Int J Biochem Cell Biol 31, 25-29
Browne GJ, Proud CG (2002) Regulation of peptide-chain elongation in mammalian
cells, Eur J Biochem 269, 5360-68
Munro JB, Sanbonmatsu KY, Spahn CMT, & Blanchard SC (2009) Navigating the
ribosome's metastable energy landscape. Trends in Biochemical Sciences, 34, 390-
400. (PDF)
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18.8 Viele Antibiotika sind Hemmer der Translation
Gaynor M, Mankin AS (2003) Macrolide antibiotics: binding site, mechanism of
action, resistance, Curr Top Med Chem 3, 949-961
Ippolito JA, Kanyo ZF, Wang DP, Franceschi FJ, Moore PB, Steitz TA, & Duffy EM
(2008) Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S
ribosomal subunit. Journal of Medicinal Chemistry, 51, 3353-3356.
19 Posttranslationale Prozessierung und Sortierung von Proteinen
19.1 Zellen sortieren Proteine nach der Translation
Saibil HR, Ranson N (2002) The chaperonin folding machine, Trends Biochem Sci
27, 627-632
Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent
chain to folded protein, Science 295, 1852-1858
Appenzeller-Herzog C & Hauri HP (2006) The ER-Golgi intermediate compartment
(ERGIC): in search of its identity and function. Journal of Cell Science, 119, 2173-
2183. (PDF)
Saibil HR (2008) Chaperone machines in action. Current Opinion in Structural
Biology, 18, 35-42.
Mayer MP (2010) Gymnastics of Molecular Chaperones. Molecular Cell, 39, 321-331.
19.2 Signalsequenzen dirigieren Proteine zu Mitochondrien
Neupert W & Herrmann JM (2007) Translocation of proteins into mitochondria.
Annual Review of Biochemistry, 76, 723-749.
Schmidt O, Pfanner N, & Meisinger C (2010) Mitochondrial protein import: from
proteomics to functional mechanisms. Nature Reviews Molecular Cell Biology, 11,
655-667.
19.3 Nucleäre Proteine tragen Kernlokalisationssequenzen
Fahrenkrog B et al (2004) The nuclear pore complex, a jack of all trades ?, Trends
Biochem Sci 29, 174-182
Tran EJ & Wente SR (2006) Dynamic nuclear pore complexes: Life on the edge. Cell,
125, 1041-1053.
Stewart M (2007) Molecular mechanism of the nuclear protein import cycle. Nature
Reviews Molecular Cell Biology, 8, 195-208.
Walde S & Kehlenbach RH (2010) The Part and the Whole: functions of nucleoporins
in nucleocytoplasmic transport. Trends in Cell Biology, 20, 461-469.
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19.4 Signalsequenzen lotsen Ribosomen zum endoplasmatischen Reticulum
Doudna JA, Batey RT (2004) Strucural Insights into the Signal Recognition Particle,
Annu Rev Biochem 73, 539-57
Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic
reticulum and bacterial plasma membranes. Nature, 450, 663-669.
Kraut-Cohen J & Gerst JE (2010) Addressing mRNAs to the ER: cis sequences act
up! Trends in Biochemical Sciences, 35, 459-469.
19.5 Transfersequenzen regulieren den Proteineinbau in Membranen
Hessa T, Meindl-Beinker NM, Bernsel A, Kim H, Sato Y, Lerch-Bader M, Nilsson I,
White SH, & von Heijne G (2007) Molecular code for transmembrane-helix
recognition by the Sec61 translocon. Nature, 450, 1026-10U2.
White SH & von Heijne G (2008) How translocons select transmembrane helices.
Annual Review of Biophysics, 37, 23-42.
19.6 Posttranslationale Modifikationen verleihen Proteinen neue Funktionen
Kleizen B, Braakman I (2004) Protein folding and quality control in the endoplasmic
reticulum, Curr Opin Cell Biol 16, 343-349
Ni M & Lee AS (2007) ER chaperones in mammalian development and human
diseases. Febs Letters, 581, 3641-3651. (PDF)
Orlean P & Menon AK (2007) GPI anchoring of protein in yeast and mammalian cells,
or: how we learned to stop worrying and love glycophospholipids. Journal of Lipid
Research, 48, 993-1011. (PDF)
19.7 Lysosomale Proteine erhalten ein Sortierungssignal
Barr FA (2002) The golgi apparatus: going round in circles ?, Trends Cell Biol 12,
101-104
Bonifacino JS, Traub LM (2003) Signals for Sorting of Transmembrane Proteins to
Endosomes and Lysosomes, Annu Rev Biochem 72, 395-447
39
Zhang M, Chen L, Wang SC, & Wang TL (2009) Rab7: roles in membrane trafficking
and disease. Bioscience Reports, 29, 193-209.
19.8 Terminale Glykosylierungen laufen im medialen Golgi ab
Ohtsubo K & Marth JD (2006) Glycosylation in cellular mechanisms of health and
disease. Cell, 126, 855-867.
Molinari M (2007) N-glycan structure dictates extension of protein folding or onset of
disposal. Nature Chemical Biology, 3, 313-320.
19.9 Vesikulärer Transport ist spezifisch und gerichtet
Bonifacino JS, Traub LM (2003) Signals for Sorting of Transmembrane Proteins to
Endosomes and Lysosomes, Annu Rev Biochem 72, 395-447
Edeling MA, Smith C, & Owen D (2006) Life of a clathrin coat: insights from clathrin
and AP structures. Nature Reviews Molecular Cell Biology, 7, 32-44.
McNiven MA (2006) Big gulps: specialized membrane domains for rapid receptor-
mediated endocytosis. Trends in Cell Biology, 16, 487-492.
19.10 Kleine G-Proteine regeln den vesikulären Transport
Haucke V (2003) Vesicle budding: a coat for the COPs, Trends Cell Biol 13, 59-60
Nie Z et al (2003) ARF and its many interactors, Curr Opin Cell Biol 15, 396-404
Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, & Chapman ER (2006)
SV2 is the protein receptor for botulinum neurotoxin A. Science, 312, 592-596.
Hsu VW, Lee SY, & Yang JS (2009) The evolving understanding of COPI vesicle
formation. Nature Reviews Molecular Cell Biology, 10, 360-364.
Beck R, Ravet M, Wieland FT, & Cassel D (2009) The COPI system: Molecular
mechanisms and function. Febs Letters, 583, 2701-2709.
19.11 Ubiquitin reguliert den Abbau cytosolischer Proteine
Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway:
destruction for the sake of construction, Physiol Rev 82, 373-428
40
41
Hartmann-Petersen R et al (2003) Transferring substrates to the 26S proteasome,
Trends Biochem Sci 28, 26-31
Nandi D, Tahiliani P, Kumar A, & Chandu D (2006) The ubiquitin-proteasome system.
Journal of Biosciences, 31, 137-155. (PDF)
Mogk A, Schmidt R, & Bukau B (2007) The N-end rule pathway for regulated
proteolysis: prokaryotic and eukaryotic strategies. Trends in Cell Biology, 17, 165-
172.
20 Kontrolle der Genexpression
20.1 Ein Komplex aus allgemeinen Transkriptionsfaktoren platziert die RNA-Polymerase
Davidson I (2003) The genetics of TBP and TBP-related factors, Trends Biochem Sci
28, 391-398
Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, & Hume DA (2007)
Mammalian RNA polymerase II core promoters: insights from genome-wide studies.
Nature Reviews Genetics, 8, 424-436.
Torres-Padilla ME & Tora L (2007) TBP homologues in embryo transcription: who
does what? Embo Reports, 8, 1016-1018. (PDF)
Baumann M, Pontiller J, & Ernst W (2010) Structure and Basal Transcription
Complex of RNA Polymerase II Core Promoters in the Mammalian Genome: An
Overview. Molecular Biotechnology, 45, 241-247.
20.2 Spezifische Transkriptionsfaktoren binden an definierte DNA-Segmente
Struhl K (1989) Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eucaryotic
transcriptional regulatory proteins, Trends Biochem Sci 14, 137-140
Laniel MA et al (2001) Electrophoretic mobility shift assays for the analysis of DNA-
protein interactions, Methods Mol Biol 148, 13-30
Laity JH et al (2001) Zinc finger proteins: new insights into structural and functional
diversity, Curr Opin Struct Biol 11, 39-46
Wasserman WW & Sandelin A (2004) Applied bioinformatics for the identification of
regulatory elements. Nature Reviews Genetics, 5, 276-287.
20.3 HTH-Proteine binden an palindromische Sequenzen
Martinez P, Amemiya CT (2002) Genomics of the HOX gene cluster, Comp Biochem
Physiol B Biochem Mol Biol 133, 571-580
Hombria JC, Lovegrove B (2003) Beyond homeosis–HOX function in morphogenesis
and organogenesis, Differentiation 71, 461-76
42
Lemons D & McGinnis W (2006) Genomic evolution of Hox gene clusters. Science,
313, 1918-1922.
20.4 Hormonrezeptoren gehören zur Klasse der Zinkfingerproteine
Li L et al (2004) Gene regulation by SP1 and SP3, Biochem Cell Biol 82, 460-471
Novac N, Heinzel T (2004) Nuclear receptors: overview and classification,
Curr Drug Targets Inflamm Allergy 3, 335-46
Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, & Mackay JP (2007) Sticky
fingers: zinc-fingers as protein-recognition motifs. Trends in Biochemical Sciences,
32, 63-70.
Siu YT & Jin DY (2007) CREB - a real culprit in oncogenesis. Febs Journal, 274,
3224-3232.
20.5 Enhancer und Silencer sitzen weitab vom Promoter
Dhillon N, Kamakaka RT (2002) Breaking through to the other side: silencers and
barriers, Curr Opin Genet Dev 12, 188-192
Cao A, Moi P (2002) Regulation of the globin genes, Pediatr Res 51, 415-21
Valenzuela L & Kamakaka RT (2006) Chromatin insulators. Annual Review of
Genetics, 40, 107-138.
Bushey AM, Dorman ER, & Corces VG (2008) Chromatin Insulators: Regulatory
Mechanisms and Epigenetic Inheritance. Molecular Cell, 32, 1-9. (PDF)
20.6 Posttranslationale Modifikationen steuern die Funktion von Transkriptionsfaktoren
Benayoun BA & Veitia RA (2009) A post-translational modification code for
transcription factors: sorting through a sea of signals. Trends in Cell Biology, 19, 189-
197.
43
44
20.7 Chemische Modifikation von Histonen reguliert die Expression von Genen
Carrozza MJ et al (2003) The diverse functions of histone acetyltransferase
complexes, Trends Genet 19, 321-9
Peterson CL, Laniel MA (2004) Histones and histone modifications, Curr Biol 27,
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Lee KK & Workman JL (2007) Histone acetyltransferase complexes: one size doesn't
fit all. Nature Reviews Molecular Cell Biology, 8, 284-295.
Li B, Carey M, & Workman JL (2007) The role of chromatin during transcription. Cell,
128, 707-719.
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification
maps. Nature Reviews Genetics, 8, 286-298.
20.8 Die Methylierung von CG-reichen Regionen inaktiviert Gene
Wilkins JF, Haig D (2003) What good is genomic imprinting: the function of parent-
specific gene expression, Nature Rev Gen 4, 1-10
Hermann A et al (2004) Biochemistry and biology of mammalian DNA
methyltransferases, Cell Mol Life Sci 61, 2571-87.
Klose RJ & Bird AP (2006) Genomic DNA methylation: the mark and its mediators.
Trends in Biochemical Sciences, 31, 89-97.
Suzuki MM & Bird A (2008) DNA methylation landscapes: provocative insights from
epigenomics. Nature Reviews Genetics, 9, 465-476.
21 Replikation – Kopieren genetischer Information
21.1 Die DNA-Replikation ist semikonservativ
Davey MJ, O´Donnell M (2000) Mechanisms of DNA replication, Curr Opin Chem Biol
4, 581-586
Bell SP, Dutta A (2002) DNA Replication in Eucaryotic Cells, Annu Rev Biochem 71,
333-74
Masai H, Matsumoto S, You ZY, Yoshizawa-Sugata N, & Oda M (2010) Eukaryotic
Chromosome DNA Replication: Where, When and How? ANNUAL REVIEWS, PALO
ALTO.
21.2 Origin-bindende Proteine eröffnen die Replikation
Gilbert DM (2001) Making sense of eukaryotic DNA replication origins, Science 294,
96-100 (PDF)
Soultanas P, Wigley DB (2001) Unwinding the ´Gordian knot´ of helicase action,
Trends Biochem Sci 26, 47-54
Mott ML & Berger JM (2007) DNA replication initiation: mechanisms and regulation in
bacteria. Nature Reviews Microbiology, 5, 343-354.
Singleton MR, Dillingham MS, & Wigley DB (2007) Structure and mechanism of
helicases and nucleic acid translocases. Annual Review of Biochemistry, 76, 23-50.
21.3 Die Synthese des Folgestrangs läuft über mehrere Stufen
Frick DN, Richardson CC (2001) DNA primases, Annu Rev Biochem 70, 39-80
O´Donnell M et al (2001) Clamp loader structure predicts the architecture of DNA
polymerase III holoenzyme and RFC, Curr Biol 11, R935-R946
Hübscher U et al (2002) Eukaryotic DNA polymerases, Annu Rev Biochem 71, 133-
163
45
21.4 Telomerase vervollständigt das 5´-Ende eines Folgestrangs
Kelleher C et al (2002) Telomerase, biochemical considerations for enzyme and
substrate, Trends Biochem Sci 27, 572-579
Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nature
Reviews Genetics, 8, 299-309.
Paeschke K, McDonald KR, & Zakian VA (2010) Telomeres: Structures in need of
unwinding. Febs Letters, 584, 3760-3772.
21.5 Die Replikation verläuft mit bemerkenswerter Präzision
Kunkel TA, Bebenek K (2004) DNA Replication Fidelity, Annu Rev Biochem 69, 497-
529
Diffley JF (2004) Regulation of early events in chromosome replication, Curr Biol 14,
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McCulloch SD & Kunkel TA (2008) The fidelity of DNA synthesis by eukaryotic
replicative and translesion synthesis polymerases. Cell Research, 18, 148-161.
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Bloom LB (2009) Loading clamps for DNA replication and repair. Dna Repair, 8,
570-578. (PDF)
21.6 Die postreplikative Korrektur gewährleistet eine hohe Präzision
Schofield MJ, Hsieh P (2003) DNA mismatch repair: molecular mechanisms and
biological functions, Annu Rev Microbiol 57, 579-608
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Modrich P (2006) Mechanisms in eukaryotic mismatch repair. Journal of Biological
Chemistry, 281, 30305-30309. (PDF)
Burgers PMJ (2009) Polymerase Dynamics at the Eukaryotic DNA Replication Fork.
Journal of Biological Chemistry, 284, 4041-4045. (PDF)
21.7 Topoisomerasen entwinden DNA-Stränge
Espeli O, Marians KJ (2004) Untangling intracellular DNA topology, Mol Microbiol 52,
925-931
46
47
Schvarzman JB, Stasniak A (2004) A topological view of the replicon, EMBO Report
5, 256-261 (PDF)
Nitiss JL (2009) DNA topoisomerase II and its growing repertoire of biological
functions. Nature Reviews Cancer, 9, 327-337. (PDF)
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Reviews Cancer, 9, 338-350. (PDF)
21.8 Nucleosomen werden während der Replikation neu verteilt
Mello JA, Almouzni G (2001) The ins and outs of nucleosome assembly, Curr Opin
Genet Dev 11, 136-141
Saha A, Wittmeyer J, & Cairns BR (2006) Chromatin remodelling: the industrial
revolution of DNA around histones. Nature Reviews Molecular Cell Biology, 7, 437-
447.
Groth A, Rocha W, Verreault A, & Almouzni G (2007) Chromatin challenges during
DNA replication and repair. Cell, 128, 721-733.
22 Analyse und Manipulation von Nucleinsäuren
22.1 Restriktionsendonucleasen spalten DNA an definierten Stellen
Nathans D, Smith HO (1975) Restriction endonucleases in the analysis and
restructuring of DNA molecules, Annu Rev Biochem 44, 273-293
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applications, Mol Biotechnol 23, 225-243
Orlowski J & Bujnicki JM (2008) Structural and evolutionary classification of Type II
restriction enzymes based on theoretical and experimental analyses. Nucleic Acids
Research, 36, 3552-3569. (PDF)
22.2 DNA-Moleküle können rekombiniert werden
Cohen S et al (1973) Construction of biologically functional bacterial plasmids in vitro,
Proc Natl Acad Sci USA 70, 3240-44 (PDF)
Kan CC (2002) Impact of recombinant DNA technology and protein engineering on
structure-based drug design: case studies of HIV-1 and HCMV proteases, Curr Top
Med Chem 2, 247-269
Milligan G et al (2004) G protein-coupled receptor fusion proteins in drug discovery,
Curr Pharm Des 10, 1989-2001
Zuo PJ & Rabie ABM (2010) One-step DNA Fragment Assembly and Circularization
for Gene Cloning. Current Issues in Molecular Biology, 12, 11-16. (PDF)
22.3 Gezielter Kettenabbruch ermöglicht die Sequenzierung von DNA
Sanger F et al (1977) DNA sequencing with chain-terminating inhibitors, Proc Natl
Acad Sci USA 74, 5463-67 (Website)
Itakura K et al (1984) Synthesis and use of synthetic oligonucleotides, Annu Rev
Biochem 53, 323-356
Franca LT et al (2002) A review of DNA sequencing techniques, Q Rev Biophys 35,
169-200
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26, 1135-1145.
48
22.4 Nucleinsäuren können miteinander hybridisieren
Southern EM (1975) Detection of specific sequences among DNA fragments
separated by gel electrophoresis, J Mol Biol 98, 503-517
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genomic Southern blot probes. Bmc Genomics, 11. (PDF)
22.5 Die Hybridisierung ermöglicht eine chromosomale Lokalisation
Liehr T, Claussen U (2002) Current developments in human molecular cytogenetic
techniques, Curr Mol Med 2, 283-297
Jenkins G (2003) Unfolding large-scale maps, Genome 46, 947-952
Bartlett JM (2004) Fluorescence in situ hybridization: technical overview, Methods
Mol Med 97, 77-78
Langer S et al (2004) Multicolor chromosome painting in diagnostic and research,
Chromosome Res 12, 15-23
Jain KK (2004) Current status of fluorescent in-situ hybridisation, Med Device
Technol 15, 14-17
22.6 Die Polymerasekettenreaktion vervielfältigt definierte DNA-Abschnitte
Arnheim N, Erlich H (1992) Polymerase chain reaction strategy, Annu Rev Biochem
61, 131-156.
Mocellin S et al (2003) Quantitative real-time PCR: a powerful ally in cancer
research, Trends Mol Med 9, 189-195
Jobling MA, Gill P (2004) Encoded evidence: DNA in forensic analysis, Nature Rev
Gen 5, 739-750
VanGuilder HD, Vrana KE, & Freeman WM (2008) Twenty-five years of quantitative
PCR for gene expression analysis. Biotechniques, 44, 619-626. (PDF)
49
22.7 DNA-Bibliotheken erlauben die Identifizierung unbekannter Gene
Shizuya H et al (1992) Cloning and stable maintenance of 300 kbp fragments of
human DNA in E.coli using an F-factor-based vector, Proc Natl Acad Sci USA 89,
8794-97 (PDF)
Ying SY (2004) Complementary DNA libraries: an overview, Mol Biotechnol 27, 245-
252
Kasai K & Saeki Y (2006) DNA-based methods to prepare helper virus-free herpes
amplicon vectors and versatile design of amplicon vector plasmids. Current Gene
Therapy, 6, 303-314.
22.8 Polymorphismen helfen beim Auffinden krankheitsrelevanter Gene
Cullis CA (2002) The use of DNA polymorphisms in genetic mapping, Genet Eng 24,
179-189
Ogino S, Wilson RB (2004) Spinal muscular atrophy: molecular genetics and
diagnostics, Expert Rev Mol Diagn 4, 15-29
Altshuler D, Daly MJ, & Lander ES (2008) Genetic Mapping in Human Disease.
Science, 322, 881-888. (PDF)
22.9 Rekombinant exprimierte Proteine werden therapeutisch eingesetzt
Andersen DC, Krummen L (2002) Recombinant protein expression for therapeutic
applications, Curr Opin Biotechnol 13, 117-123
Kastrup J (2003) Therapeutic angiogenesis in ischemic heart disease: gene or
recombinant vascular growth factor protein therapy? Curr Gene Ther 3, 197-206
Walsh G & Jefferis R (2006) Post-translational modifications in the context of
therapeutic proteins. Nature Biotechnology, 24, 1241-1252.
22.10 Gezielte Mutagenese hilft bei der Aufklärung von Proteinfunktionen
Kristiansen K (2004) Molecular mechanisms of ligand binding, signaling, and
regulation within the superfamily of G-protein-coupled receptors: molecular modeling
and mutagenesis approaches to receptor structure and function, Pharmacol Ther
103, 21-80
50
de Graaf C, Oostenbrink C, Keizers PHJ, van Vugt-Lussenburg BMA, van
Waterschoot RAB, Tschirret-Guth RA, Commandeur JNM, & Vermeulen NPE (2007)
Molecular modeling-guided site-directed mutagenesis of cytochrome P450 2D6.
Current Drug Metabolism, 8, 59-77.
Yan Z, Sun X, & Engelhardt JF (2009) Progress and prospects: techniques for site-
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51
23 Veränderung genetischer Information
23.1 Transition und Transversion sind häufige Substitutionen
Courtois G & Gilmore TD (2006) Mutations in the NF-kappa B signaling pathway:
implications for human disease. Oncogene, 25, 6831-6843.
23.2 Die Reparatur von DNA erfolgt prompt und effizient
Sancar A et al (2004) Molecular Mechanisms of Mammalian DNA Repair and the
DNA Damage Checkpoints, Annu Rev Biochem 73, 39-85
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Molecular Life Sciences, 63, 1266-1277.
Wyman C & Kanaar R (2006) DNA double-strand break repair: All's well that ends
well. Annual Review of Genetics, 40, 363-383.
23.3 Eliminierende Reparatursysteme sichern die Integrität der Erbinformationen
Moriwaki S, Kraemer KH (2001) Xeroderma pigmentosum – bridging a gap between
clinic and laboratory, Photodermatol Photoimmunol Photomed 17: 47-54
Sinha RP, Hader DP (2002) UV-induced DNA damage and repair: a review,
Photochem Photobiol Sci 1, 225-236
Cleaver JE (2005) Cancer in xeroderma pigmentosum and related disorders of DNA
repair. Nature Reviews Cancer, 5, 564-573.
Reardon JT & Sancar A (2006) Purification and characterization of Escherichia coli
and human nucleotide excision repair enzyme systems. Elsevier Academic Press
Inc., San Diego.
23.4 Die Neuverknüpfung von DNA sorgt für genetische Variabilität
Petronczki M et al (2003) Un ménage a quatre: the molecular biology of chromosome
segregation in meiosis, Cell 112, 423-440
52
Lynn A et al (2004) Variation in human meiotic recombination, Annu Rev Genomics
Hum Genet 5, 317-349
Liu Y, West SC (2004) Happy Hollidays: 40th anniversery of the Holliday junction,
Nat Rev Mol Cell Biol 5, 937-946
Neale MJ & Keeney S (2006) Clarifying the mechanics of DNA strand exchange in
meiotic recombination. Nature, 442, 153-158.
23.5 Die Auflösung der Strangkreuzung kann auf zwei Wegen erfolgen
Yamada K et al (2004) Three-dimensional structural views of branch migration and
resolution in DNA homologous recombination, Curr Opin Struct Biol 14, 130-137
Griffin CS, Thacker J (2004) The role of homologous recombination repair in the
formation of chromosome aberrations, Cytogenet Genome Res 104, 21-27
Cox MM (2007) Motoring along with the bacterial RecA protein. Nature Reviews
Molecular Cell Biology, 8, 127-138.
23.6 Die Antikörperdiversität beruht auf ortsgerichteter Rekombination
Oettinger MA (2004) How to keep V(D)J recombination under control, Immunol Rev
200, 165-181
Jung D, Giallourakis C, Mostoslavsky R, & Alt FW (2006) Mechanism and control of
V(D)J recombination at the immunoglobulin heavy chain locus. Annual Review of
Immunology, 24, 541-570.
Di Nola JM & Neuberger MS (2007) Molecular mechanisms of antibody somatic
hypermutation. Annual Review of Biochemistry, 76, 1-22.
Hewitt SL, Chaumeil J, & Skok JA (2010) Chromosome dynamics and the regulation
of V(D)J recombination. Immunological Reviews, 237, 43-54.
23.7 Ortsgerichtete Rekombination erzeugt die Vielfalt von T-Zell-Rezeptoren
Jones JM, Gellert M (2004) The taming of a transposon: V(D)J recombination and the
immune systeme, Immunol Rev 200, 233-248
Hersh MN et al (2004) Adaptive mutation and amplification in Escherichia coli: two
pathways of genome adaptation under stress, Res Microbiol 155, 352-359
53
Odegard VH & Schatz DG (2006) Targeting of somatic hypermutation. Nature
Reviews Immunology, 6, 573-583.
23.8 Transposons sind mobile Genelemente
Kazazian HH Jr (2004) Mobile elements: drivers of genome evolution, Science 303,
1626-32
Levy SB, Marshall B (2004) Antibacterial resistance worldwide: causes, challenges
and responses, Nat Med 10, S122-129
Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy
P, Morgante M, Panaud O, Paux E, SanMiguel P, & Schulman AH (2007) A unified
classification system for eukaryotic transposable elements. Nature Reviews
Genetics, 8, 973-982.
23.9 Retroviren integrieren ihre DNA in das Wirtsgenom
Wu X, Burgess SM (2004) Integration target site selection for retroviruses and
transposable elements, Cell Mol Life Sci 61, 2588-96
Bennett PM (2004) Genome plasticity: insertion sequence elements, transposons and
integrons, and DNA rearrangement, Methods Mol Biol 266, 71-113
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5, 253-263.
Balvay L, Lastra ML, Sargueil B, Darlix JL, & Ohlmann T (2007) Translational control
of retroviruses. Nature Reviews Microbiology, 5, 128-140.
23.10 Transgene Tiere gestatten die funktionelle Analyse ausgewählter Genprodukte
Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA,
Nature 431, 343-349
Medema RH (2004) Optimizing RNA interference for application in mammalian cells,
Biochem.J. 380, 593-603 (PDF)
Recillas-Targa F (2006) Multiple strategies for gene transfer, expression, knockdown,
and chromatin influence in mammalian cell lines and transgenic animals. Molecular
Biotechnology, 34, 337-354.
54
Venkatesh MN (2008) Transgenic animals and current scenario. Research Journal of
Biotechnology, 3, 53-63. (PDF)
23.11 Gentherapie ermöglicht die Behandlung von ererbten Erkrankungen
Gaspar HB et al (2003) Gene therapy progress and prospects: gene therapy for
severe combined immunodeficiency, Gene Ther 10, 1999-2004
Li SD & Huang L (2006) Gene therapy progress and prospects: non-viral gene
therapy by systemic delivery. Gene Therapy, 13, 1313-1319.
Waehler R, Russell SJ, & Curiel DT (2007) Engineering targeted viral vectors for
gene therapy. Nature Reviews Genetics, 8, 573-587.
23.12 Der Mensch entschlüsselt sein eigenes Genom
Austin CP (2004) The impact of the completed human genome sequence on the
development of novel therapeutics for human disease, Annu Rev Med 55, 1-13
Eichler EE et al (2004) An assessment of the sequence gaps: unfinished business in
a finished humane genome, Nat Rev Genet 5, 345-354
Nielsen R, Hellmann I, Hubisz M, Bustamante C, & Clark AG (2007) Recent and
ongoing selection in the human genome. Nature Reviews Genetics, 8, 857-868.
(PDF)
55
Teil IV Signaltransduktion an biologischen Membranen
24 Struktur und Dynamik biologischer Membranen
24.1 Phospholipide bilden in wässriger Lösung spontan Doppelschichten
Nagle JF, Tristram-Nagle S (2000) Lipid bilayer structure, Curr Opin Struct Biol 110,
474-480 (PDF)
Monnard PA, Deamer DW (2002) Membrane self-assembly processes: steps toward
the first cellular life, Anat Rec 268, 196-207 (PDF)
Carmona-Ribeiro AM (2006) Lipid bilayer fragments and disks in drug delivery.
Current Medicinal Chemistry, 13, 1359-1370.
Feigenson GW (2009) Phase diagrams and lipid domains in multicomponent lipid
bilayer mixtures. Biochimica et Biophysica Acta-Biomembranes, 1788, 47-52. (PDF)
24.2 Biologische Membranen sind dynamische Strukturen
Jacbson K et al (1995) Revisiting the fluid mosaic model of membranes, Science
268, 1441-42
Bagatolli LA (2006) To see or not to see: Lateral organization of biological
membranes and fluorescence microscopy. Biochimica et Biophysica Acta-
Biomembranes, 1758, 1541-1556.
van Meer G, Voelker DR, & Feigenson GW (2008) Membrane lipids: where they are
and how they behave. Nature Reviews Molecular Cell Biology, 9, 112-124. (PDF)
Elson EL, Fried E, Dolbow JE, & Genin GM (2010) Phase Separation in Biological
Membranes: Integration of Theory and Experiment. ANNUAL REVIEWS, PALO
ALTO.
24.3 Lipidmembranen verfügen über eine selektive Permeabilität
Holsbeeks I et al (2004) The eukaryotic plasma membrane as a nutrient-sensing
device, Trends Biochem Sci 29, 556-564
56
Chen RRZ (2007) Permeability issues in whole-cell bioprocesses and cellular
membrane engineering. Applied Microbiology and Biotechnology, 74, 730-738.
24.4 Biologische Membranen sind asymmetrisch und geladen
Devaux PF, Morris R (2004) Transmembrane asymmetry and lateral domains in
biological membranes, Traffic 5, 241-246
Fadeel B & Xue D (2009) The ins and outs of phospholipid asymmetry in the plasma
membrane: roles in health and disease. Critical Reviews in Biochemistry and
Molecular Biology, 44, 264-277. (PDF)
24.5 Das endoplasmatische Reticulum produziert asymmetrische Membranen
Sanyat S & Menon AK (2009) Flipping Lipids: Why an' What's the Reason for? Acs
Chemical Biology, 4, 895-909.
Contreras FX, Sanchez-Magraner L, Alonso A, & Goni FM (2010) Transbilayer (flip-
flop) lipid motion and lipid scrambling in membranes. Febs Letters, 584, 1779-1786.
24.6 Die Verteilung von Lipiden und Proteinen in biologischen Membranen schwankt
Parton RG, Hancock JF (2004) Lipid rafts and plasma membrane microorganization:
insights from Ras, Trends Cell Biol 14, 141-147
Hancock JF (2006) Lipid rafts: contentious only from simplistic standpoints. Nature
Reviews Molecular Cell Biology, 7, 456-462. (PDF)
Jacobson K, Mouritsen OG, & Anderson RGW (2007) Lipid rafts: at a crossroad
between cell biology and physics. Nature Cell Biology, 9, 7-14.
Parton RG & Simons K (2007) The multiple faces of caveolae. Nature Reviews
Molecular Cell Biology, 8, 185-194.
24.7 Funktionelle Membransysteme können rekonstituiert werden
Silvius JR (1992) Solubilization and functional reconstitution of biomembrane
components, Annu Rev Biophys Biomol Struct 21, 323-348
57
58
Seddon AM et al (2004) Membrane proteins, lipids and detergents: not just a soap
opera, Biochim Biophys Acta 1666, 105-117
Liguori L & Lenormand JL (2009) Production of Recombinant Proteoliposomes for
Therapeutic Uses. Elsevier Academic Press Inc., San Diego.
Ritchie TK, Grinkova YV, Bayburt TH, Denisov IG, Zolnerciks JK, Atkins WM, &
Sligar SG (2009) Reconstitution of Membrane Proteins in Phospholipid Bilayer
Nanodiscs. Elsevier Academic Press Inc., San Diego.
25 Proteine als Funktionsträger von Biomembranen
25.1 Integrale Proteine durchspannen biologische Membranen
Doura AK, Fleming KG (2004) Complex interactions at the helix-helix interface
stabilize the glycophorin A transmembrane dimer, J Mol Biol 343,1487-97
Opin Struct Biol 8, 640-648
MacKenzie KR (2006) Folding and stability of alpha-helical integral membrane
proteins. Chemical Reviews, 106, 1931-1977.
Speers AE & Wu CC (2007) Proteomics of integral membrane proteins-theory and
application. Chemical Reviews, 107, 3687-3714.
25.2 Periphere Membranproteine binden einseitig an die Lipidschicht
Linder ME, Deschenes RJ (2003) New insights into the mechanisms of protein
palmitoylation, Biochem 42, 4311-20
Resh MD (2004) Membrane targeting of lipid modified signal transduction proteins,
Subcell Biochem 37, 217-32
Cheng TL & Roffler S (2008) Membrane-Tethered Proteins for Basic Research,
Imaging, and Therapy. Medicinal Research Reviews, 28, 885-928.
25.3 Membranproteine bewegen sich in der Lipidschicht
Jaskolski F & Henley JM (2009) Synaptic Receptor Trafficking: the Lateral Point of
View. Neuroscience, 158, 19-24.
Rayan G, Guet JE, Taulier N, Pincet F, & Urbach W (2010) Recent Applications of
Fluorescence Recovery after Photobleaching (FRAP) to Membrane Bio-
Macromolecules. Sensors, 10, 5927-5948. (PDF)
25.4 Membranproteine verleihen Membranen ihre funktionelle Vielfalt
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60
Sperandio M (2006) Selectins and glycosyltransferases in leukocyte rolling in vivo.
Febs Journal, 273, 4377-4389.
25.5 Transportproteine vermitteln regen Stoffaustausch über Membranen
Huang Y & Sadee W (2006) Membrane transporters and channels in
chemoresistance and -sensitivity of tumor cells. Cancer Letters, 239, 168-182.
25.6 Transport über Membranen kann uni- oder bidirektional sein
Philipson KD, Nicoll DA (2000) Sodium-calcium exchange: a molecular approach,
Annu Rev Physiol 62, 111-133
Zhao FQ & Keating AF (2007) Functional properties and genomics of glucose
transporters. Current Genomics, 8, 113-128. (PDF)
Abramson J & Wright EM (2009) Structure and function of Na+-symporters with
inverted repeats. Current Opinion in Structural Biology, 19, 425-432.
25.7 Pumpen und Kanäle schleusen Ionen über Membranbarrieren
Jentsch T et al (2004) Ion channels: function unravelled by dysfunction, Nature Cell
Biol 6, 1039-37
DeFelice LJ (2004) Going against the flow, Nature 432, 279
Piddock LJ (2006) Multidrug-resistance efflux pumps - not just for resistance. Nature
Reviews Microbiology, 4, 629-636.
Tadini-Buoninsegni F, Bartolornmei G, Moncelli MR, & Fendler K (2008) Charge
transfer in P-type ATPases investigated on planar membranes. Archives of
Biochemistry and Biophysics, 476, 75-86.
26 Ionenpumpen und Membrankanäle
26.1 Die Na+-K+-ATPase arbeitet im Antiport-Modus
Kaplan JH (2002) Biochemistry of NA,K-ATPase, Annu Rev Biochem 71, 511-35
Jorgensen PL et al (2003) Structure and mechanism of Na,K-ATPase: Functional
sites and their interaction, Annu Rev Physiol 66, 817-849
Poulsen H, Morth P, Egebjerg J, & Nissen P (2010) Phosphorylation of the Na+,K+-
ATPase and the H+,K+-ATPase. Febs Letters, 584, 2589-2595.
26.2 Ionengradienten treiben den Stofftranport über Membranen an
Toyoshima C, InesiI G (2004) Strucural Basis of Ion Pumping by Ca2+-ATPase of the
Sarcoplasmic Reticulum, Annu Rev Biochem 73, 269-92
Toyoshima C (2008) Structural aspects of ion pumping by Ca2+-ATPase of
sarcoplasmic reticulum. Archives of Biochemistry and Biophysics, 476, 3-11.
26.3 Protonentransporter entsorgen die zellulären H+-Lasten
Subramaniam S (1999) The structure of bacteriorhodopsin: an emerging consensus,
Curr Opin Struct Biol 9, 462-468
Padan E, Kozachkov L, Herz K, & Rimon A (2009) NhaA crystal structure: functional-
structural insights. Journal of Experimental Biology, 212, 1593-1603.
Hirai T, Subramaniam S, & Lanyi JK (2009) Structural snapshots of conformational
changes in a seven-helix membrane protein: lessons from bacteriorhodopsin. Current
Opinion in Structural Biology, 19, 433-439. (PDF)
Tian P (2010) Computational protein design, from single domain soluble proteins to
membrane proteins. Chemical Society Reviews, 39, 2071-2082.
26.4 ABC-Transporter verfrachten Ionen, Lipide und Arzneimittel über Membranen
McCarty NA (2000) Permeation through the CFTR chloride channel, J Exp Biol 203,
1947-62 (PDF)
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Borst P, Elferink RO (2002) Mammalian ABC Transporters in Health and Disease,
Annu Rev Biochem 71, 537-92
Guggino WB & Stanton BA (2006) New insights into cystic fibrosis: molecular
switches that regulate CFTR. Nature Reviews Molecular Cell Biology, 7, 426-436.
Rees DC, Johnson E, & Lewinson O (2009) ABC transporters: the power to change.
Nature Reviews Molecular Cell Biology, 10, 218-227. (PDF)
26.5 Ionenkanäle bilden temporäre Poren in der Membran
Miloshevsky GV, Jordan PC (2004) Permeation in ion channels: the interplay
between structure and theory, Trends Neurosci 27, 308-314
Owsianik G, Talavera K, Voets T, & Nilius B (2006) Permeation and selectivity of
TRP channels. Annual Review of Physiology, 68, 685-717.
26.6 Spannungsgesteuerte Ionenkanäle sondieren Potenzialänderungen
Kaczmarek LK (2006) Non-conducting functions of voltage-gated ion channels.
Nature Reviews Neuroscience, 7, 761-771.
Dai SP, Hall DD, & Hell JW (2009) Supramolecular Assemblies and Localized
Regulation of Voltage-Gated Ion Channels. Physiological Reviews, 89, 411-452.
(PDF)
26.7 Der nicotinische Acetylcholinrezeptor ist ein ligandengesteuerter Ionenkanal
Utkin Y et al (2000) Structural organization of nicotinic acetylcholin receptors, Membr
Cell Biol 13, 143-164
Miyazawa A et al (2003) Structure and gating mechanism of the acetylcholin receptor
pore, Nature 432, 949-955
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Nicotinic Acetylcholine Receptors: From Structure to Function. Physiological
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26.8 Liganden steuern die Öffnung der Rezeptorschleuse
Neher E, Sakmann B (1992) The patch-clamp technique, Sci Am 266(3), 28-35
Maksay G (2009) Ligand-gated pentameric ion channels, from binding to gating. Curr
Mol Pharmacol, 2.
26.9 Zellporen erlauben den Stoffaustausch zwischen Nachbarzellen
Unger VM et al (1999) Three-dimensional structure of a recombinant gap junction
membrane channel, Science 283, 1176-1180
Stout C et al (2004) Connexins: functions without junctions, Curr Opin Cell Biol 16:
507-512
Bloomfield SA & Volgyi B (2009) The diverse functional roles and regulation of
neuronal gap junctions in the retina. Nature Reviews Neuroscience, 10, 495-506.
27 Prinzipien der interzellulären Kommunikation
27.1 Interzelluläre Kommunikation nutzt mehrere Modalitäten
Drucker DJ (2007) The role of gut hormones in glucose homeostasis. Journal of
Clinical Investigation, 117, 24-32. (PDF)
27.2 Endokrine Signalsysteme sind selektiv, amplifizierend und flexibel
Bokoch MP, Zou YZ, Rasmussen SGF, Liu CW, Nygaard R, Rosenbaum DM, Fung
JJ, Choi HJ, Thian FS, Kobilka TS, Puglisi JD, Weis WI, Pardo L, Prosser RS,
Mueller L, & Kobilka BK (2010) Ligand-specific regulation of the extracellular surface
of a G-protein-coupled receptor. Nature, 463, 108-U121. (PDF)
27.3 Fundamentale Signalwege vermitteln die interzelluläre Kommunikation
Taniguchi CM, Emanuelli B, & Kahn CR (2006) Critical nodes in signalling pathways:
insights into insulin action. Nature Reviews Molecular Cell Biology, 7, 85-96.
Pilecka I, Whatmore A, van Huijsduijnen RH, Destenaves B, & Clayton P (2007)
Growth hormone signalling: sprouting links between pathways, human genetics and
therapeutic options. Trends in Endocrinology and Metabolism, 18, 12-18.
27.4 Intrazelluläre Rezeptoren wirken als Transkriptionsfaktoren
Dilworth FJ, Chambon P (2001) Nuclear receptors coordinate the activities of
chromatin remodeling complexes and coactivators to facilitate initiation of
transcription, Oncogene 20, 3047-3054 (PDF)
Evans R (2004) A transcriptional basis for physiology, Nat Med 10, 1022-1026
Bain DL, Heneghan AF, Connaghan-Jones KD, & Miura MT (2007) Nuclear receptor
structure: Implications for function. Annual Review of Physiology, 69, 201-220.
Cheng SY, Leonard JL, & Davis PJ (2010) Molecular Aspects of Thyroid Hormone
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64
27.5 Stickstoffmonoxid ist ein gasförmiger Botenstoff
Bredt DS (2003) Nitric oxide signaling specificity – the heart of the problem, J Cell Sci
1, 9-15 (PDF)
Moncada S & Bolanos JP (2006) Nitric oxide, cell bioenergetics and
neurodegeneration. Journal of Neurochemistry, 97, 1676-1689.
Cary SPL, Winger JA, Derbyshire ER, & Marletta MA (2006) Nitric oxide signaling: no
longer simply on or off. Trends in Biochemical Sciences, 31, 231-239.
27.6 Proteohormone werden aus inaktiven Vorstufen freigesetzt
Tanaka S (2004) Comparative aspects of intracellular proteolytic processing of
peptide hormone precursors: studies of proopiomelanocortin processing, Zoolog Sci
20,1183-1198
Michael DJ, Cai HJ, Xiong WY, Ouyang J, & Chow RH (2006) Mechanisms of
peptide hormone secretion. Trends in Endocrinology and Metabolism, 17, 408-415.
27.7 Zelloberflächenrezeptoren aktivieren intrazelluläre Signalkaskaden
Scott JD, Pawson T (2000) Cell Communication, The Inside Story, Sci Amer 282,
June: 54-61
Schlessinger J & Lemmon MA (2006) Nuclear signaling by receptor tyrosine kinases:
The first robin of spring. Cell, 127, 45-48.
Hanson MA & Stevens RC (2009) Discovery of New GPCR Biology: One Receptor
Structure at a Time. Structure, 17, 8-14. (PDF)
27.8 GTP-bindende Proteine verknüpfen Signalketten
Neves SR et al (2002) G protein pathways, Science 296, 1636-1639
Bos JL, Rehmann H, & Wittinghofer A (2007) GEFs and GAPs: Critical elements in
the control of small G proteins. Cell, 129, 865-877.
Marrari Y, Crouthamel M, Irannejad R, & Wedegaertner PB (2007) Assembly and
trafficking of heterotrimeric G proteins. Biochemistry, 46, 7665-7677. (PDF)
Gasper R, Meyer S, Gotthardt K, Sirajuddin M, & Wittinghofer A (2009) It takes two to
tango: regulation of G proteins by dimerization. Nature Reviews Molecular Cell
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27.9 Effektoren integrieren Signale verschiedener Rezeptoren
Tan X et al (2003) Integration of G-protein coupled receptor signaling pathways for
activation of a transcription factor (EGR-3). Genomics Proteomics Bioinformatics 1,
173-179
Tiyyagura SR et al (2004) Reciprocal regulation and integration of signaling by
intracellular calcium and cyclic GMP, Vitam Horm 69, 69-94
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Reviews Immunology, 8, 559-568. (PDF)
Milano A, De Rosa V, Iaffaioli RV, & Caponigro F (2007) Downstream intracellular
effectors of epidermal growth factor receptor as targets for anticancer therapy. Expert
Opinion on Therapeutic Targets, 11, 771-782.
28 Signaltransduktion über G-Protein-gekoppelte Rezeptoren
28.1 G-Protein-gekoppelte Rezeptoren durchspannen siebenmal die Membran
Ross EM, Wilkie TM (2000) GTPase-Activating Proteins for Heterotrimeric G
Proteins, Regulators of G Protein Signaling (RGS) and RGS-like Proteins, Annu Rev
Biochem 69, 795-827 (PDF)
Dohlman HG, Thorner JW (2001) Regulation of G-Protein-Initiated Signal
Transduction in Yeast, Paradigms and Principles, Annu Rev Biochem 70, 703-54
Congreve M & Marshall F (2010) The impact of GPCR structures on pharmacology
and structure-based drug design. British Journal of Pharmacology, 159, 986-996.
28.2 G-Proteine modulieren die Aktivität von Adenylat-Cyclase
Lencer WI, Tsai B (2003) The intracellular voyage of cholera toxin, going retro,
Trends Biochem Sci 28, 639-645
Rebois RV, Robitaille M, Gales C, Dupre DJ, Baragli A, Trieu P, Ethier N, Bouvier M,
& Hebert TE (2006) Heterotrimeric G proteins form stable complexes with adenylyl
cyclase and Kir3.1 channels in living cells. Journal of Cell Science, 119, 2807-2818.
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Willoughby D & Cooper DMF (2007) Organization and Ca2+ regulation of adenylyl
cyclases in cAMP microdomains. Physiological Reviews, 87, 965-1010. (PDF)
28.3 Kinasen phosphorylieren und desensitivieren G-Protein-gekoppelte Rezeptoren
Ribas C et al (2007) The G protein-coupled receptor kinase (GRK) interactome: Role
of GRKs in GPCR regulation and signaling. Biochimica et Biophysica Acta-
Biomembranes, 1768, 913-922.
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28.4 Die Rezeptorendocytose benutzt clathrinbeschichtete Vesikel
Marchese A et al (2003) The ins and outs of G-protein-coupled receptor trafficking,
Trends Biochem Sci 28, 369-376
McNiven MA & Thompson HM (2006) Vesicle formation at the plasma membrane
and trans-Golgi network: The same but different. Science, 313, 1591-1594.
Wolfe BL & Trejo J (2007) Clathrin-dependent mechanisms of G protein-coupled
receptor endocytosis. Traffic, 8, 462-470.
28.5 cAMP steuert über Transkriptionsfaktoren die Genexpression
Brivanlou AH, Darnell JE (2002) Signal transduction and the control of gene
expression, Science 295, 813-818
Kitagawa K (2007) CREB and cAMP response element-mediated gene expression in
the ischemic brain. Febs Journal, 274, 3210-3217.
Benito E & Barco A (2010) CREB's control of intrinsic and synaptic plasticity:
implications for CREB-dependent memory models. Trends in Neurosciences, 33,
230-240.
28.6 Sinneszellen nutzen G-Protein-abhängige Signalwege
Buck LB (2000) The molecular architecture of odor and pheromone sensing in
mammals, Cell 100, 611-618
Ridge KD et al (2003) Phototransduction, crystal clear, Trends Biochem Sci 28, 479-
487
Palczewski K (2006) G protein-coupled receptor rhodopsin. Annual Review of
Biochemistry, 75, 743-767. (PDF)
Yau KW & Hardie RC (2009) Phototransduction Motifs and Variations. Cell, 139, 246-
264. (PDF)
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Circuits. Cell, 139, 45-59.
28.7 Inositoltrisphosphat setzt Ca2+ aus intrazellulären Speichern frei
Patterson RL et al (2004) Inositol 1,4,5-Trisphosphate Receptors as Signal
Integrators, Annu Rev Biochem 73, 437-64
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Carafolie E (2004) Calcium-mediated cellular signals, a story of failures, Trends
Biochem Sci 29, 371-379
Mikoshiba K (2007) IP3 receptor/Ca2+ channel: from discovery to new signaling
concepts. Journal of Neurochemistry, 102, 1426-1446.
Joseph SK & Hajnoczky G (2007) IP3 receptors in cell survival and apoptosis: Ca2+
release and beyond. Apoptosis, 12, 951-968.
28.8 Ca2+ und Calmodulin wirken im Duett
Chin D, Means AR (2000) Calmodulin : a prototypical calcium sensor, Trends Cell
Biol 10, 322-328
Corcoran EE, Means AR (2001) Defining Ca2+/calmodulin-dependent protein kinase
cascades in transcriptional regulation, J Biol Chem 276, 2975-78 (PDF)
Al-Shanti N & Stewart CE (2009) Ca2+/calmodulin-dependent transcriptional
pathways: potential mediators of skeletal muscle growth and development. Biological
Reviews, 84, 637-652.
28.9 Diacylglycerin aktiviert Proteinkinase C
Spitaler M, Cantrell DA (2004) Protein kinase C and beyond, Nat Immunol 5, 785-790
Newton AC (2004) Diacylglycerol's affair with protein kinase C turns 25, Trends
Pharmacol Sci 25, 175-177
Wang QMJ (2006) PKD at the crossroads of DAG and PKC signaling. Trends in
Pharmacological Sciences, 27, 317-323.
29 Signaltransduktion über enzymgekoppelte Rezeptoren
29.1 Enzymgekoppelte Rezeptoren besitzen meist Tyrosin-Kinase-Aktivität
Schlessinger J (2000) Cell signaling by receptor tyrosin kinases, Cell 103,211-225
Cross MJ et al (2003) VEGF-receptor signal transduction, Trends Biochem Sci 28,
488-494
Dengjel J, Kratchmarova I, & Blagoev B (2009) Receptor tyrosine kinase signaling: a
view from quantitative proteomics. Molecular Biosystems, 5, 1112-1121.
29.2 Liganden induzieren Dimerisierung und Autophosphorylierung
Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation
of EGF receptor, Cell 110, 669-672
Bae JH & Schlessinger J (2010) Asymmetric tyrosine kinase arrangements in
activation or autophosphorylation of receptor tyrosine kinases. Molecules and Cells,
29, 443-448.
29.3 Enzymgekoppelte Rezeptoren aktivieren monomere G-Proteine
Corbett KD, Alber T (2001) The many faces of Ras, recognition of small GTP-binding
proteins, Trends Biochem Sci 26, 710-716
Harden TK & Sondek J (2006) Regulation of phospholipase C isozymes by Ras
superfamily GTPases. Annual Review of Pharmacology and Toxicology, 46, 355-379.
Karnoub AE & Weinberg RA (2008) Ras oncogenes: split personalities. Nature
Reviews Molecular Cell Biology, 9, 517-531.
29.4 GTP-Ras aktiviert den MAP-Kinasen-Signalweg
Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades, Nature 410,
37-40
Buchwalter G, Gross C, & Wasylyk B (2004) Ets ternary complex transcription
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Dhillon AS, Hagan S, Rath O, & Kolch W (2007) MAP kinase signalling pathways in
cancer. Oncogene, 26, 3279-3290.
29.5 Mutierte Signalproteine haben onkogenes Potenzial
Blume-Jensen P, Hunter T (2001) Oncogenic kinase signaling, Nature 411, 355-365
Rajalingam K, Schreck R, Rapp UR, & Albert S (2007) Ras oncogenes and their
downstream targets. Biochimica et Biophysica Acta-Molecular Cell Research, 1773,
1177-1195.
Krab LC, Goorden SMI, & Elgersma Y (2008) Oncogenes on my mind: ERK and
MTOR signaling in cognitive diseases. Trends in Genetics, 24, 498-510.
29.6 Cytokine benutzen Tyrosin-Kinase-assoziierte Rezeptoren
Attisano L, Wranna JL (2002) Signal transduction by the TGF- β superfamily, Science
296, 1646-47
Aaronson DS, Horvath CM (2002) A roadmap for those who don´t know JAK-STAT,
Science 296, 1653-55
Schindler C, Levy DE, & Decker T (2007) JAK-STAT signaling: From interferons to
cytokines. Journal of Biological Chemistry, 282, 20059-20063. (PDF)
Steinberg GR, Watt MJ, & Febbraio MA (2009) Cytokine regulation of AMPK
signalling. Frontiers in Bioscience, 14, 1902-1916.
29.7 Integrine sind zellmatrixassoziierte Rezeptoren
Humphries MJ et al (2003) Integrin structure, heady advances in ligand binding, but
activation still makes the knees wobble, Trends Biochem Sci 28/6, 313-320
Fagerholm S et al (2004) P marks the spot, site-specific integrin phosphorylation
regulates molecular interactions, Trends Biochem Sci 29, 504-512
Arnaout MA, Goodman SL, & Xiong JP (2007) Structure and mechanics of integrin-
based cell adhesion. Current Opinion in Cell Biology, 19, 495-507. (PDF)
Gahmberg CG, Fagerholm SC, Nurmi SM, Chavakis T, Marchesan S, & Gronholm M
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30 Hormonelle Steuerung komplexer Systeme
30.1 Regulation des kardiovaskulären Systems
Lowenstein CJ (2007) Nitric oxide regulation of protein trafficking in the
cardiovascular system. Cardiovascular Research, 75, 240-246. (PDF)
Hendriks-Balk MC, Peters SLM, Michel MC, & Alewijnse AE (2008) Regulation of G
protein-coupled receptor signalling: Focus on the cardiovascular system and
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278-291.
30.2 Regulation von Wasser- und Elektrolythaushalt
Ruilope LM (2008) Angiotensin receptor blockers: RAAS blockade and
renoprotection. Current Medical Research and Opinion, 24, 1285-1293.
Brown D, Hasler U, Nunes P, Bouley R, & Lu HAJ (2008) Phosphorylation events
and the modulation of aquaporin 2 cell surface expression. Current Opinion in
Nephrology and Hypertension, 17, 491-498.
30.3 Steuerung von Calcium- und Phosphathaushalt
Wada T, Nakashima T, Hiroshi N, & Penninger JM (2006) RANKL-RANK signaling in
osteoclastogenesis and bone disease. Trends in Molecular Medicine, 12, 17-25.
30.4 Molekulare Basis von Wachstum und Entwicklung
Kurmasheva RT & Houghton PJ (2006) IGF-I mediated survival pathways in normal
and malignant cells. Biochimica et Biophysica Acta-Reviews on Cancer, 1766, 1-22.
Sami AJ (2007) Structure-function relation of somatotropin with reference to
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30.5 Hormonelle Regulation in reproduktiven Sytemen
Hunzicker-Dunn M & Maizels ET (2006) FSH signaling pathways in immature
granulosa cells that regulate target gene expression: Branching out from protein
kinase A. Cellular Signalling, 18, 1351-1359. (PDF)
Palermo R (2007) Differential actions of FSH and LH during folliculogenesis.
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31 Molekulare Physiologie des Gastrointestinaltrakts
31.1 Hormonelle Regelwerke im Magen
Kusters JG, van Vliet AHM, & Kuipers EJ (2006) Pathogenesis of Helicobacter pylori
infection. Clinical Microbiology Reviews, 19, 449-90. (PDF)
Forte JG & Zhu LX (2010) Apical Recycling of the Gastric Parietal Cell H,K-ATPase.
Annual Review of Physiology, 72, 273-296.
31.2 Molekulare Mechanismen von Digestion und Resorption
Lomer MCE, Parkes GC, & Sanderson JD (2008) Review article: lactose intolerance
in clinical practice - myths and realities. Alimentary Pharmacology & Therapeutics,
27, 93-103. (PDF)
Borghese MFA & Majowicz MP (2009) Inhibitors of Sodium/Glucose Cotransport.
Drugs of the Future, 34, 297-305.
31.3 Hormonelle Steuerung des exokrinen Pankreas
Alrefai WA & Gill RK (2007) Bile acid transporters: Structure, function, regulation and
pathophysiological implications. Pharmaceutical Research, 24, 1803-1823.
Czako L, Hegyi P, Rakonczay Z, Wittmann T, & Otsuki M (2009) Interactions
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31.4 Hormonelle Steuerung des Glucosemetabolismus
Bansal P & Wang QH (2008) Insulin as a physiological modulator of glucagon
secretion. American Journal of Physiology-Endocrinology and Metabolism, 295,
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32 Neuronale Erregung und Transmission
32.1 An der Zellmembran entsteht ein Ruhepotenzial
Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its
application to conduction and excitation in nerve, J Physiol 117, 500-544 (PDF)
Sundelacruz S, Levin M, & Kaplan DL (2009) Role of Membrane Potential in the
Regulation of Cell Proliferation and Differentiation. Stem Cell Reviews and Reports,
5, 231-246.
32.2 Der K+-Gradient bestimmt vorwiegend das Ruhepotenzial
Kurata HT & Fedida D (2006) A structural interpretation of voltage-gated potassium
channel inactivation. Progress in Biophysics & Molecular Biology, 92, 185-208.
Ashcroft FM (2006) From molecule to malady. Nature, 440, 440-447.
32.3 Nervenzellen können auf einen Reiz mit einem Aktionspotenzial reagieren
Acebes A, Ferrus A (2000) Cellular and molecular features of axon collaterals and
dendrites, Trends Neurosci 23, 557-565
Lai HC & Jan LY (2006) The distribution and targeting of neuronal voltage-gated ion
channels. Nature Reviews Neuroscience, 7, 548-562.
Borjesson SI & Elinder F (2008) Structure, Function, and Modification of the Voltage
Sensor in Voltage-Gated Ion Channels. Cell Biochemistry and Biophysics, 52, 149-
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32.4 Aktionspotenziale verlaufen unidirektional, stereotyp und oft saltatorisch
Chotard C, Salecker I (2004) Neurons and glia: team players in axon guidance,
Trends Neurosci 27, 655-661
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Bean BP (2007) The action potential in mammalian central neurons. Nature Reviews
Neuroscience, 8, 451-465.
Baranauskas G (2007) Ionic Channel Function in Action Potential Generation:
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32.5 Neurotransmitter übertragen Botenschaften an chemischen Synapsen
Kiehn O, Tresch MC (2002) Gap junctions and motor behavior, Trends Neurosci 25,
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Haydon PG & Carmignoto G (2006) Astrocyte control of synaptic transmission and
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Rizo J, Chen XC, & Arac D (2006) Unraveling the mechanisms of synaptotagmin and
SNARE function in neurotransmitter release. Trends in Cell Biology, 16, 339-350.
32.6 Neurotransmitter können exzitatorisch oder inhibitorisch wirken
Mayer ML (2004) Structure and function of glutamate receptor ion channels, Annu
Rev Physiol 66, 161-181
Craig AM, Graf ER, & Linhoff MW (2006) How to build a central synapse: clues from
cell culture. Trends in Neurosciences, 29, 8-20. (PDF)
Ben-Ari Y, Gaiarsa JL, Tyzio R, & Khazipov R (2007) GABA: A pioneer transmitter
that excites immature neurons and generates primitive oscillations. Physiological
Reviews, 87, 1215-1284. (PDF)
Lau CG & Zukin RS (2007) NMDA receptor trafficking in synaptic plasticity and
neuropsychiatric disorders. Nature Reviews Neuroscience, 8, 413-426.
32.7 Katecholamine steuern elementare neuronale Prozesse
Oberbeck R (2006) Catecholamines: Physiological Immunomodulators During Health
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32.8 Neuropeptide und Toxine modulieren die synaptische Aktivität
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Nature 407, 963-970
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33 Struktur und Dynamik des Cytoskeletts
33.1 Mikrotubuli sind dynamische Strukturen des Cytoskeletts
Nogales E (2000) Structural Insights into Mikrotubule Function, Annu Rev Biochem
69, 277-302
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Akhmanova A & Steinmetz MO (2008) Tracking the ends: a dynamic protein network
controls the fate of microtubule tips. Nature Reviews Molecular Cell Biology, 9, 309-
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33.2 Intermediärfilamente verleihen mechanische Widerstandsfähigkeit
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Herrmann H, Aebi U (2004) Intermediate Filaments, Molecular Structure, Assembly
Mechanism, and Integration into Functionally Distinct Intracellular Scaffolds, Annu
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Post-translational modifications of intermediate filaments. Febs Letters, 582, 2140-
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33.3 Die Aggregation von Actin zu Filamenten ist strikt reguliert
McGough AM, Staiger CJ, Min JK, & Simonetti KD (2003) The gelsolin family of actin
regulatory proteins: modular structures, versatile functions. Febs Letters, 552, 75-81.
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33.4 Actinbindende Proteine bündeln und vernetzen Einzelfilamente
Winder SJ (2003) Structural insights into actin-binding, branching and bundling
proteins, Curr Opin Cell Biol 15, 14-22
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growth cones. Nature Reviews Neuroscience, 9, 136-147.
Khurana S & George SP (2008) Regulation of cell structure and function by actin-
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33.5 Actinfilamente formieren sich zu Gerüstwerken in der Zelle
Campbell I, Ginsberg M (2004) The talin-tail interaction places integrin activation on
FERM ground, Trends Biochem Sci 29, 429-435
Weis WI & Nelson WJ (2006) Re-solving the cadherin-catenin-actin conundrum.
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Elsaesser R & Paysan J (2007) The sense of smell, its signalling pathways, and the
dichotomy of cilia and microvilli in olfactory sensory cells. Bmc Neuroscience, 8.
33.6 Proteingerüste stabilisieren die Erythrocytenmembran
Dubreuil RR (2006) Functional links between membrane transport and the spectrin
cytoskeleton. Journal of Membrane Biology, 211, 151-161.
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33.7 Actinfilamente und Mikrotubuli bilden Schienen für Motorproteine
Cross RA (2004) The kinetic mechanism of kinesin, Trends Biochem Sci 29, 300-309
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and intracellular transport. Nature Reviews Molecular Cell Biology, 10, 682-696.
33.8 Selectine und CAM-Proteine vermitteln Zelladhäsion
Dalva MB, McClelland AC, & Kayser MS (2007) Cell adhesion molecules: signalling
functions at the synapse. Nature Reviews Neuroscience, 8, 206-220.
Sperandio M (2006) Selectins and glycosyltransferases in leukocyte rolling in vivo.
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34 Zellzyklus und programmierter Zelltod
34.1 Cycline und cyclinabhängige Kinasen steuern den eukaryotischen Zellzyklus
Kelly TJ, Brown GW (2000) Regulation of Chromosome Replication, Annu Rev
Biochem 69, 829-80
O´Connell MJ et al (2000) The G2-phase DNA-damage checkpoint, Trends Cell Biol
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lessons from genetically modified mice. Frontiers in Bioscience, 11, 1164-1188.
Musgrove EA (2006) Cyclins: Roles in mitogenic signaling and oncogenic
transformation. Growth Factors, 24, 13-19.
34.2 Aktivierung von CDK1 startet die Mitose
Hochegger H, Takeda S, & Hunt T (2008) Cyclin-dependent kinases and cell-cycle
transitions: does one fit all? Nature Reviews Molecular Cell Biology, 9, 910-U26.
Malumbres M & Barbacid M (2009) Cell cycle, CDKs and cancer: a changing
paradigm. Nature Reviews Cancer, 9, 153-166.
34.3 CDK4 kontrolliert den Restriktionspunkt in der G1-Phase
Ekholm SV & Reed SI (2000) Regulation of G(1) cyclin dependent kinases in the
mammalian cell cycle. Current Opinion in Cell Biology, 12, 676-684.
Nyberg KA et al (2002) Toward maintaining the genome: DNA damage and
replication checkpoints, Annu Rev Genet 36, 617-656
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34.4 Der Tumorsuppressor p53 moduliert die Aktivität von CDKs
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Acta 1602, 47-59
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Death and Differentiation, 13, 941-950. (PDF)
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34.5 Eine enzymatische Kaskade löst den programmierten Zelltod aus
Jiang X, Wang X (2004) Cytochrome c-mediated Apoptosis, Annu Rev Biochem 73,
87-106
Kumar S, Cakouros D (2004) Transkriptional control of the core cell-death machinery,
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Roos WP & Kaina B (2006) DNA damage-induced cell death by apoptosis. Trends in
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34.6 Caspasen spalten spezifische Funktionsproteine der Zelle
Jiang X, Wang X (2004) Cytochrome c-mediated Apoptosis, Annu Rev Biochem 73,
87-106
Shiozaki E, Yigong S (2004) Caspases, IAPs and Smac/DIABLO, mechanisms from
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Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, & Vandenabeele P (2007)
Caspases in cell survival, proliferation and differentiation. Cell Death and
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35 Molekulare Basis von Krebsentstehung und Krebsbekämpfung
35.1 Tumorzellen haben ungebremstes replikatives Potenzial
Zeng Q & Hong W (2008) The emerging role of the Hippo pathway in cell contact
inhibition, organ size control, and cancer development in mammals. Cancer Cell, 13,
188-192.
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, & Thompson CB (2008) The biology of
cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism,
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35.2 Krebs ist eine genetische Erkrankung
Jain S, Xu R, Prieto VG, Lee P (2010) Molecular classification of soft tissue
sarcomas and its clinical applications. Int J Clin Exp Pathol. 23;3(4):416-28. (PDF)
35.3 Mutagene Agenzien können Krebs auslösen
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DNA: Recent advances. Dna Repair, 6, 429-442.
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35.4 Onkogene Zellen können transformieren
Cowling VH & Cole MD (2006) Mechanism of transcriptional activation by the Myc
oncoproteins. Seminars in Cancer Biology, 16, 242-252.
Musgrove EA (2006) Cyclins: Roles in mitogenic signaling and oncogenic
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35.5 Tumorsuppressorgene wachen über die zelluläre Proliferation
Gabellini C, Del Bufalo D, & Zupi G (2006) Involvement of RB gene family in tumor
angiogenesis. Oncogene, 25, 5326-5332.
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regulated genes. Nature Reviews Molecular Cell Biology, 9, 402-412.
Kim WY & Sharpless NE (2006) The regulation of INK4/ARF in cancer and aging.
Cell, 127, 265-275.
35.6 Wachstumsfaktoren und die Signalproteine Wnt, Notch und Hedgehog steuern basale Zellfunktionen
Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nature
Reviews Molecular Cell Biology, 7, 678-689.
Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell, 127,
469-480.
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Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histology and
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35.7 p53, TGF- und Rb-Signalwege regulieren Zellteilung und -differenzierung
Bierie B & Moses HL (2006) TGF beta: the molecular Jekyll and Hyde of cancer.
Nature Reviews Cancer, 6, 506-520.
Adams JM & Cory S (2007) The Bcl-2 apoptotic switch in cancer development and
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35.8 NF-κB- und PI3K-Signalwege wachen über die Apoptose
Baud V & Jacque E (2008) The alternative NF-kappa B activation pathway and
cancer : friend or foe? M S-Medecine Sciences, 24, 1083-1088.
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35.9 Neue Ansätze in Tumordiagnostik und –therapie basieren auf molekularen Erkenntnissen
Carpi A, Mechanick JI, Saussez S, & Nicolini A (2010) Thyroid Tumor Marker
Genomics and Proteomics: Diagnostic and Clinical Implications. Journal of Cellular
Physiology, 224, 612-619.
Zhang JY & Tan EM (2010) Autoantibodies to tumor-associated antigens as
diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert
Review of Molecular Diagnostics, 10, 321-328.
Giaginis C, Vgenopoulou S, Vielh P, & Theocharis S (2010) MCM proteins as
diagnostic and prognostic tumor markers in the clinical setting. Histology and
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35.10 Molekulares Verständnis von Kanzerogenese eröffnet therapeutisches Neuland
Eskens FA & Verweij J (2006) The clinical toxicity profile of vascular endothelial
growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)
targeting angiogenesis inhibitors; A review. European Journal of Cancer, 42, 3127-
3139.
Pytel D, Sliwinski T, Poplawski T, Ferriola D, & Majsterek I (2009) Tyrosine Kinase
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36 Angeborenes und erworbenes Immunsystem
36.1 Das Komplementsystem attackiert bakterielle Invasoren
Kimbrell DA, Beutler B (2001) The evolution and genetics of innate immunity, Nat
Rev Genet 2, 256-267
Girardi G, Bulla R, Salmon JE, & Tedesco F (2006) The complement system in the
pathophysiology of pregnancy. Molecular Immunology, 43, 68-77.
Nonaka M & Kimura A (2006) Genomic view of the evolution of the complement
system. Immunogenetics, 58, 701-713. (PDF)
36.2 Der terminale Komplex stanzt Poren in die Bakterienmembran
Carroll MC (2004) The complement system in regulation of adaptive immunity, Nat
Immunol 5, 981-986
Kemper C & Atkinson JP (2007) T-cell regulation: with complements from innate
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36.3 Das natürliche Immunsystem nutzt Toll-ähnliche Rezeptoren
Janeway CA, Medzhitov R (2002) Innate immune recognition, Annu Rev Immunol 20,
197-216
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36.4 MHC-Proteine präsentieren Antigene auf der Zelloberfläche
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MHC class I and II proteins: New avenues from new methods. Molecular
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36.5 Lymphocyten bilden das Rückgrat des adaptiven Immunsystems
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36.6 T-Zellen organisieren die zellvermittelte Immunabwehr
Pitcher LA, van Oers NS (2003) T-cell receptor signal transmission: who gives an
ITAM ?, Trends Immunol 24, 554-560
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36.7 T-Helferzellen stimulieren B-Zellen
Davis MM et al (2003) Dynamics of Cell Surface Molecules During T Cell
Recognition, Annu Rev Biochem 72, 717-742
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Family. Annual Review of Immunology, 27, 519-550.
36.8 Cytotoxische T-Zellen versetzen infizierten Zellen den Todesstoß
Kloetzel PM, Ossendorp F (2004) Proteasome and peptidase function in MHC-class-
I-mediated antigen presentation, Curr Opin Immunol 16, 76-81
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that They Activate Diverse Apoptotic Pathways in Target Cells. International Reviews
of Immunology, 29, 38-55.
36.9 B-Zellen organisieren die humorale Immunantwort
Martin F & Chan AC (2006) B cell immunobiology in disease: Evolving concepts
from the clinic. Annual Review of Immunology, 24, 467-496.
Lanzavecchia A & Sallusto F (2007) Toll-like receptors and innate immunity in B-cell
activation and antibody responses. Current Opinion in Immunology, 19, 268-274.
36.10 Variable und konstante Domänen bilden die Antikörperketten
Wang W, Singh S, Zeng DL, King K, & Nema S (2007) Antibody structure, instability,
and formulation. Journal of Pharmaceutical Sciences, 96, 1-26.
Chen SW, Van Regenmortel MHV, & Pellequer JL (2009) Structure-Activity
Relationships in Peptide-Antibody Complexes: Implications for Epitope Prediction
and Development of Synthetic Peptide Vaccines. Current Medicinal Chemistry, 16,
953-964.
36.11 Somatische Hypermutation führt zur Affinitätsreifung von B-Zellen
Kinoshita K, Honjo T (2001) Linking class-switch recombination with somatic
hypermutation, Nat Rev Mol Cell Biol 2, 493-503
Odegard VH & Schatz DG (2006) Targeting of somatic hypermutation. Nature
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Di Nola JM & Neuberger MS (2007) Molecular mechanisms of antibody somatic
hypermutation. Annual Review of Biochemistry, 76, 1-22.
Peled JU, Kuang FL, Iglesias-Ussel MD, Roa S, Kalis SL, Goodman ME, & Scharff
MD (2008) The biochemistry of somatic hypermutation. Annual Review of
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37 Erforschung und Entwicklung neuer Arzeistoffe
37.1 Arzneistoffe binden an definierte Zielmoleküle
Nelson CP & Challiss RAJ (2007) "Phenotypic" pharmacology: The influence of
cellular environment on G protein-coupled receptor antagonist and inverse agonist
pharmacology. Biochemical Pharmacology, 73, 737-751.
Garcia-Lopez MT, Gonzalez-Muniz R, Martin-Martinez M, & Herranz R (2007)
Strategies for design of non peptide CCK1R agonist/antagonist ligands. Current
Topics in Medicinal Chemistry, 7, 1180-1194.
37.2 Arzneistoffe binden mit hoher Affinität an ihr Target
Ota T, Shinotoh H, Fukushi K, Kikuchi T, Sato K, Tanaka N, Shimada H, Hirano S,
Miyoshi M, Arai H, Suhara T, & Irie T (2010) Estimation of Plasma IC50 of Donepezil
for Cerebral Acetylcholinesterase Inhibition in Patients With Alzheimer Disease Using
Positron Emission Tomography. Clinical Neuropharmacology, 33, 74-78.
37.3 Die Analyse von Genomen und Proteomen liefert neue Zielmoleküle
Oh DY, Kim K, Kwon HB, & Seong JY (2006) Cellular and molecular biology of
orphan G protein-coupled receptors. Elsevier Academic Press Inc., San Diego.
Rix U & Superti-Furga G (2009) Target profiling of small molecules by chemical
proteomics. Nature Chemical Biology, 5, 616-624.
Bantscheff M, Scholten A, & Heck AJ (2009) Revealing promiscuous drug-target
interactions by chemical proteomics. Drug Discovery Today, 14, 1021-1029.
37.4 Naturstoffe dienen als Quelle neuer Arzneimittel
Lam KS (2007) New aspects of natural products in drug discovery. Trends in
Microbiology, 15, 279-289.
Molinski TF, Dalisay DS, Lievens SL, & Saludes JP (2009) Drug development from
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discovery through natural products. Expert Opinion on Drug Discovery, 5, 559-568.
37.5 Die Durchmusterung von Substanzbibliotheken liefert Arzneistoffkandidaten
Kumar RA & Clark DS (2006) High-throughput screening of biocatalytic activity:
applications in drug discovery. Current Opinion in Chemical Biology, 10, 162-168.
Snowden MA & Green DVS (2008) The impact of diversity-based, high-throughput
screening on drug discovery: "Chance favours the prepared mind". Current Opinion
in Drug Discovery & Development, 11, 553-558.
37.6 Arzneistoffe müssen resorbiert werden und in inakter Form an ihren Wirkort gelangen
de Boer AG & Breimer DD (1997) Hepatic first-pass effect and controlled drug
delivery following rectal administration. Advanced Drug Delivery Reviews, 28, 229-
237.
Chu I & Nomeir AA (2006) Utility of mass spectrometry for in-vitro ADME assays.
Current Drug Metabolism, 7, 467-477.
Ullrich R & Hofrichter M (2007) Enzymatic hydroxylation of aromatic compounds.
Cellular and Molecular Life Sciences, 64, 271-293.
37.7 Arzneistoffe müssen auf toxische Eigenschaften hin geprüft werden
Zunkler BJ (2006) Human ether-a-go-go-related (HERG) gene and ATP-sensitive
potassium channels as targets for adverse drug effects. Pharmacology &
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Chen MX, Helliwell RM, & Clare JJ (2009) In vitro profiling against ion channels
beyond hERG as an early indicator of cardiac risk. Current Opinion in Molecular
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37.8 Monoklonale Antikörper sind wirksame Biotherapeutika
Peterson E, Owens SM, & Henry RL (2006) Monoclonal antibody form and function:
Manufacturing the right antibodies for treating drug abuse. Aaps Journal, 8, E383-
E390.
Mano M & Humblet Y (2008) Drug insight: panitumumab, a human EGFR-targeted
monoclonal antibody with promising clinical activity in colorectal cancer. Nature
Clinical Practice Oncology, 5, 415-425.
Cheson BD & Leonard JP (2008) Drug therapy: Monoclonal antibody therapy for B-
cell non-Hodgkin's lymphoma. New England Journal of Medicine, 359, 613-626.
37.9 Die Arzneimitteltherapie der Zukunft ist personalisiert
van't Veer LJ & Bernards R (2008) Enabling personalized cancer medicine through
analysis of gene-expression patterns. Nature, 452, 564-570.
Zhou SF, Di YM, Chan E, Du YM, Chow VDW, Xue CCL, Lai XS, Wang JC, Li CG,
Tian M, & Duan W (2008) Clinical Pharmacogenetics and Potential Application in
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Olopade OI, Grushko TA, Nanda R, & Huo DZ (2008) Advances in Breast Cancer:
Pathways to Personalized Medicine. Clinical Cancer Research, 14, 7988-7999.
37.10 Die Entwicklung neuer Arzneistoffe ist langwierig
Adams VR & Leggas M (2007) Sunitinib malate for the treatment of metastatic renal
cell carcinoma and gastrointestinal stromal tumors. Clinical Therapeutics, 29, 1338-
1353.
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Teil V Energieumwandlung und Biosynthese
38 Grundprinzipien des Metabolismus
38.1 Biochemische Reaktionen gehorchen den Gesetzen der Thermodynamik
Halle B (2004) Protein hydration dynamics in solution: a critical survey, Philos Trans
Royal Soc 359, 1207-1224 (PDF)
Smith E, Morowitz HJ (2004) Universality in intermediary metabolism, Proc Natl Acad
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Saito N, Ohashi Y, Soga T, & Tomita M (2010) Unveiling cellular biochemical
reactions via metabolomics-driven approaches. Current Opinion in Microbiology, 13,
358-362.
38.2 ATP ist der universelle Energieüberträger
Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends in
Pharmacological Sciences, 27, 166-176.
38.3 NADH und FADH2 sind die wichtigsten Elektronenüberträger
Lin H (2007) Nicotinamide adenine dinucleotide: beyond a redox coenzyme. Organic
& Biomolecular Chemistry, 5, 2541-2554.
Wos ML & Pollard PC (2009) Cellular nicotinamide adenine dinucleotide (NADH) as
an indicator of bacterial metabolic activity dynamics in activated sludge. Water
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38.4 Coenzym A ist der wichtigste Überträger von Acylgruppen
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Hereditary and acquired diseases of acyl-coenzyme A metabolism. Molecular
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Spry C, Kirk K, & Saliba KJ (2008) Coenzyme A biosynthesis: an antimicrobial drug
target. Fems Microbiology Reviews, 32, 56-106.
38.5 Katabole Wege münden in den Citratzyklus
Owen OE et al (2002) The key role of anaplerosis and cataplerosis for citric acid
cycle function, J Biol Chem 277, 30409-30412 (PDF)
Fernie AR et al (2004) Respiratory metabolism: glycolysis, the TCA cycle and
mitochondrial electron transport, Curr Opin Plant Biol 7, 254-261
38.6 Die Regulation der Stoffwechselprozesse erfolgt multilateral
Jafri MS et al (2001) Cardiac energy metabolism: models of cellular respiration, Annu
Rev Biomed Eng 3, 57-81
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39 Glykolyse – Prototyp eines Stoffwechselwegs
39.1 Der glykolytische Weg läuft über zehn Stationen
Heinrich R et al (1999) The structural design of glycolysis: an evolutionary approach,
Biochem Soc Trans. 27, 294-298
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39.2 Die Bildung von Glycerinaldehyd-3-phosphat kostet ATP
Dunaway GA (1983) A review of animal phosphofructokinase isozymes with an
emphasis on their pysiological role, Mol Cell Biochem. 52, 75-91
Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular
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39.3 Die Oxidation von Glycerinaldehyd-3-phosphat liefert ATP
Berry MD & Boulton AA (2000) Glyceraldehyde-3-phosphate dehydrogenase and
apoptosis. Journal of Neuroscience Research, 60, 150-154.
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39.4 Die Erzeugung von Pyruvat ist an ATP-Gewinn geknüpft
Sugden MC & Holness MJ (2003) Recent advances in mechanisms regulating
glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.
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39.5 Die Energiebilanz der Glykolyse ist positiv
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39.6 Weitere Kohlenhydrate werden in den glykolytischen Weg eingeschleust
Novelli G & Reichardt JKV (2000) Molecular basis of disorders of human galactose
metabolism: Past, present, and future. Molecular Genetics and Metabolism, 71, 62-
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Michels PAM & Rigden DJ (2006) Evolutionary analysis of fructose 2,6-bisphosphate
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39.7 Die Glykolyse wird engmaschig kontrolliert
van de Werve G, Lange A, Newgard C, Mechin MC, Li YZ, & Berteloot A (2000) New
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Mader A (2003) Glcolysis and oxidative phosphorylation as a function of cytosolic
phosphorylation state and power output of the muscle cell, Eur J Appl Physiol 88,
317-338
Wu CD, Khan SA, & Lange AJ (2005) Regulation of glycolysis - role of insulin.
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40 Citratzyklus – zentrale Drehscheibe des Metabolismus
40.1 Die oxidative Decarboxylierung von Pyruvat liefert Acetyl-CoA
Zhou ZH et al (2001) The remarkable structural and functional organization of
the eucaryotic pyruvate dehydrogenase complexes, PNAS 98, 14802-14807
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mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.
Cellular and Molecular Life Sciences, 64, 830-849.
40.2 Der Citratzyklus ist eine geschlossene Folge von neun Einzelreaktionen
Huynen MA et al (1999) Variation and evolution of the citric-acid cycle: a genomic
perspective, Trends Microbiol 7, 281-291
Aoshima M (2007) Novel enzyme reactions related to the tricarboxylic acid cycle:
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40.3 Oxidoreduktasen liefern die Reduktionsäquivalente NADH und FADH2
May SW (1999) Applications of oxidoreductases. Current Opinion in Biotechnology,
10, 370-375.
Cecchini G, Maklashina E, Yankovskaya V, Iverson TM, & Iwata S (2003) Variation in
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40.4 Der Citratzyklus bedient katabole und anabole Wege
Gibala MJ et al (2000) Anaplerosis of the citric acid cycle: role in energy metabolism of
heart and skeletal muscle, Acta Physiol Scand 168, 657-665
Owen OE, Kalhan SC, & Hanson RW (2002) The key role of anaplerosis and
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40.5 Der Citratzyklus unterliegt einer stringenten Kontrolle
Krebs HA (1970) Rate control of the tricarboxylic acid cycle, Adv Enzyme Regul. 8,
335-353
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41 Oxidative Phosphorylierung – Elektronentransport und ATP-
Synthese
41.1 Cytosolisches NADH gelangt über Umwege in die Atmungskette
Minarik P et al (2002) Malate dehydrogenase - - structure and function, Gen Physiol
Biophys 21, 257-265 (PDF)
Li YJ, Dash RK, Kim JY, Saidel GM, & Cabrera ME (2009) Role of NADH/NAD(+)
transport activity and glycogen store on skeletal muscle energy metabolism during
exercise: in silico studies. American Journal of Physiology-Cell Physiology, 296, C25-
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41.2 Die oxidative Phosphorylierung verläuft in zwei Pasen
Saraste M (1999) Oxidative phosphorylation at the fin de siecle, Science 283, 1488-
1493
Kerr DS (2010) Treatment of mitochondrial electron transport chain disorders: A
review of clinical trials over the past decade. Molecular Genetics and Metabolism, 99,
246-255.
41.3 Komplex I schleust Elektronen von NADH in die Atmungskette ein
Brandt U (2006) Energy converting NADH : Quinone oxidoreductase (Complex I).
Annual Review of Biochemistry, 75, 69-92.
Lenaz G, Fato R, Formiggini G, & Genova ML (2007) The role of Coenzyme Q in
mitochondrial electron transport. Mitochondrion, 7, S8-S33.
41.4 Verschiedene FAD-abhängige Dehydrogenasen bilden weitere Zuflüsse zur Atmungskette
Scrutton NS, Sutcliffe MJ (2000) Trimethylamine dehydrogenase and electron
transferring flavoprotein, Subcell Biochem. 35, 145-181
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from electron transferring flavoproteins and partner complexes. Febs Journal, 274,
5481-5504.
41.5 Cytochrom c-Reduktase überträgt Elektronen auf Cytochrom c
Hunte C et al (2003) Protonmotive pathways and mechnisms in the cytochrome bc1
complex, FEBS Lett 545, 39-46
Crofts AR (2004) The cytochrome bc1 complex: function in the context of structure,
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Crofts AR, Lhee S, Crofts SB, Cheng J, & Rose S (2006) Proton pumping in the bc(1)
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Covian R & Trumpower BL (2008) Regulatory interactions in the dimeric cytochrome
bc(1) complex: The advantages of being a twin. Biochimica et Biophysica Acta-
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41.6 Cytochrom c-Oxidase überträgt Elektronen auf molekularen Sauerstoff
Michel H (1999) Cytochrome c oxidase: catalytic cycle and mechanism of proton
pumping - - a discussion, Biochemistry 38, 15129-15140
Richter OM, Ludwig B (2003) Cytochrome c oxidase - - structure, function, and
physiology of a redox driven machine, Rev Physiol Biochem Pharmacol 147, 47-74
Wikstrom M (2004) Cytochrome c oxidase: 25 years of the elusive proton pump,
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Qin L, Sharpe MA, Garavito RM, & Ferguson-Miller S (2007) Conserved lipid-binding
sites in membrane proteins: a focus on cytochrome c oxidase. Current Opinion in
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41.7 Elektronentransport und Phosphorylierung sind gekoppelt
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1493
Huttemann M, Lee I, Pecinova A, Pecina P, Przyklenk K, & Doan JW (2008)
Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and
their role in human disease. Journal of Bioenergetics and Biomembranes, 40, 445-
456.
41.8 Ein Nano-Rotationsmotor synthetisiert ATP
Boyer PD (2002) Catalytic occupancy during ATP synthase catalysis, FEBS Lett 512,
29-32
Weber J, Senior AE (2003) ATP synthesis driven by proton transport in F1F0-ATP
synthase, FEBS Lett 545, 61-70
Nakamoto RK, Scanlon JAB, & Al-Shawi MK (2008) The rotary mechanism of the
ATP synthase. Archives of Biochemistry and Biophysics, 476, 43-50. (PDF)
von Ballmoos C, Cook GM, & Dimroth P (2008) Unique rotary ATP synthase and its
biological diversity. Annual Review of Biophysics, 37, 43-64.
41.9 Eine Translokase lässt Nucleotide über Membranen fließen
Palmieri L et al (2000) Yeast mitochondrial carriers: bacterial expression, biochemical
identification and metabolic significance, J Bioenerg Biomembr 32, 67-77
Halestrap AP, Brennerb C (2003) The adenine nucleotide translocase: a central
component of the mitochondrial permeability transition pore and key player in cell
death, Curr Med Chem 10, 1507-1525
Dorner A & Schultheiss HP (2007) Adenine nucleotide translocase in the focus of
cardiovascular diseases. Trends in Cardiovascular Medicine, 17, 284-290.
41.10 Entkoppler verursachen einen Kurzschluss der Protonenbatterie
Kadenbach B (2003) Intrinsic and extrinsic uncoupling of oxidative phosphorylation,
Biochim Biophys Acta 1604, 77-94
Cannon B und Nedergaard J (2004) Brown adipose tissue: function and physiological
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Kovacic P, Pozos RS, Somanathan R, Shangari N, & O'Brien PJ (2005) Mechanism
of mitochondrial uncouplers, inhibitors, and toxins: Focus on electron transfer, free
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2623.
41.11 Die Verbrennung von 1 Mol Glucose erzeugt bis zu 30 Mol ATP
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analysis of some mechanisms affecting the yield of oxidative phosphorylation:
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42 Pentosephosphatweg- ein adaptives Stoffwechselmodul
42.1 Der Pentosephosphatweg läuft in zwei Phasen ab
Kruger NJ, von Schaewen A (2003) The oxidative pentose phosphate pathway:
structure and organisation,Curr Opin Plant Biol 6, 236-46
Huck JH et al (2003) Profiling of pentose phosphate pathway intermediates in blood
spots by tandem mass spectrometry: application to transaldolase deficiency, Clin
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Gupte SA (2008) Glucose-6-phosphate dehydrogenase: A novel therapeutic target in
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Bolanos JP, Almeida A, & Moncada S (2010) Glycolysis: a bioenergetic or a survival
pathway? Trends in Biochemical Sciences, 35, 145-149.
42.2 Die oxidative Phase liefert NADPH und Ribulose-5-phosphat
Duffieux F et al (2000) Molecular characterization of the first two enzymes of the
pentose-phosphate pathway of Trypanosoma brucei. Clucose-6-phosphate
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Ho HY, Cheng ML, & Chiu DTY (2007) Glucose-6-phosphate dehydrogenase - from
oxidative stress to cellular functions and degenerative diseases. Redox Report, 12,
109-118.
Cappellini MD & Fiorelli G (2008) Gluclose-6-phosphate dehydrogenase deficiency.
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42.3 Die nichtoxidative Phase interkonvertiert Kohlenhydrate
Kochetov GA (2001) Functional flexibility of the transketolase molecule, Biochemistry
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42.4 Der Pentosephosphatweg dient wechselnden zellulären Bedürfnissen
Siems WG et al (2000) Erythrocyte free radical and energy metabolism, Clin Nephrol
53(1 Suppl), 9-17
Tozzi MG, Camici M, Mascia L, Sgarrella F, & Ipata PL (2006) Pentose phosphates
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43 Gluconeogenese und Cori-Zyklus
43.1 Die Gluconeogenese läuft über elf enzymatische Stationen
Hers HG, Hue L (1983) Gluconeogenesis and related aspects of glycolysis, Annu
Rev Biochem 52, 617-53
Nuttall FQ, Ngo A, & Gannon MC (2008) Regulation of hepatic glucose production
and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?
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43.2 Eine transiente Carboxylierung führt über Oxalacetat zum Phosphoenolpyruvat
Delbaere LT et al (2004) Structure/function studies of phosphoryl transfer by
phosphoenolpyruvate carboxykinase, Biochim Biophys Acta 1697, 271-8
Jitrapakdee S, St Maurice M, Rayment I, Cleland WW, Wallace JC, & Attwood PV
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43.3 Zwei Phosphatasen sind Schlüsselenzyme der Gluconeogenese
Foster JD, Nordlie RC (2002) The biochemistry and molecular biology of the glucose-
6-phosphatase system, Exp Biol Med (Maywood) 227, 601-8 (PDF)
van Sschaftingen E, Gerin I (2002) The glucose-6-phosphatase system, Biochem J
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van Poelje PD, Dang Q, & Erion MD (2007) Discovery of fructose-1,6-
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Hutton JC & O'Brien RM (2009) Glucose-6-phosphatase Catalytic Subunit Gene
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43.4 Glykolyse und Gluconeogenese werden reziprok reguliert
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461-7
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Yalcin A, Telang S, Clem B, & Chesney J (2009) Regulation of glucose metabolism
by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer. Experimental
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43.5 Der Cori-Zyklus verbindet muskuläre Glykolyse und hepatische Gluconeogenese
Katz J, Tayek JA (1999) Recycling of glucose and determination of the Cori Cycle
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44 Biosynthese und Abbau von Glykogen
44.1 Glykogen ist ein verzweigtes Glucosepolymer
Roach PJ (2002) Glycogen and its metabolism, Curr Mol Med 2, 101-20
Shearer J, Graham TE (2002) New perspectives on the storage and organization of
muscle glycogen, Can J Appl Physiol 27, 179-203
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Gastroenterology, 13, 2541-2553. (PDF)
44.2 Die Glykogensynthese läuft über vier enzymatische Stationen
Melendez R, Melendez-Hevia E and Cascante M (1997) How did glycogen structure
evolve to satisfy the requirement for rapid mobilzation of glucose? A problem of
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Ballicora MA, Iglesias AA, & Preiss J (2003) ADP-glucose pyrophosphorylase, a
regulatory enzyme for bacterial glycogen synthesis. Microbiology and Molecular
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Agius L (2008) Glucokinase and molecular aspects of liver glycogen metabolism.
Biochemical Journal, 414, 1-18.
44.3 Glykogen-Synthase ist das Schlüsselenzym beim Aufbau von Glykogen
Lomako J et al (2004) Glycogenin: the primer for mammalian and yeast glycogen
synthesis, Biochim Biophys Acta 1673, 45-55
Weinstein DA, Correia CE, Saunders AC, & Wolfsdorf JI (2006) Hepatic glycogen
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44.4 Eine Transglykosylase verzweigt wachsende Glykogenketten
Abad MC et al (2002) The X-ray crystallographic structure of Escherichia coli
branching enzyme, J Biol Chem 277, 42164-70 (PDF)
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44.5 Die Glykogenolyse umfasst fünf enzymatische Stationen
Bollen M et al (1998) Specific features of glycogen metabolism in the liver, Biochem
J, 336, 19-31 (PDF)
Greenberg CC, Jurczak MJ, Danos AM, & Brady MJ (2006) Glycogen branches out:
new perspectives on the role of glycogen metabolism in the integration of metabolic
pathways. American Journal of Physiology-Endocrinology and Metabolism, 291, E1-
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44.6 Glykogen-Phosphorylase ist das Schlüsselenzym der Glykogenolyse
Livanova NB et al (2002) Pyridoxal 5’-phosphate as a catalytic and conformational
cofactor of muscle glycogen phosphorylase B, Biochemistry (Mosc) 67, 1089-98
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Somsak L, Czifrak K, Toth M, Bokor E, Chrysina ED, Alexacou KM, Hayes JM,
Tiraidis C, Lazoura E, Leonidas DD, Zographos SE, & Oikonomakos NG (2008) New
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Medicinal Chemistry, 15, 2933-2983.
Richard JP, Amyes TL, Crugeiras J, & Rios A (2009) Pyridoxal 5 '-phosphate:
electrophilic catalyst extraordinaire. Current Opinion in Chemical Biology, 13, 475-
483.
44.7 Ein bifunktionelles Enzym entzweigt Glykogen
Nakayama A et al (2001) Identification of the catalytic residues of bifunctional
glycogen debranching enzyme, Biol Chem 276, 28824-8 (PDF)
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44.8 Störungen des Glykogenabbaus führen zu Speicherkrankheiten
Chen YT et al (2002) Prenatal diagnosis in glycogen storage diseases, Prenat Diagn
22, 357-9
Wolfsdorf JI, Weinstein DA (2003) Glycogen storage diseases, Rev Endocr Metab
Disord 4, 95-102
Koeberl DD, Kishnani PS, Bali D, & Chen YT (2009) Emerging therapies for glycogen
storage disease type I. Trends in Endocrinology and Metabolism, 20, 252-258.
44.9 Hormonelle Signale steuern den Glykogenstoffwechsel
Yeaman SJ et al (2001) Regulation of glycogen synthesis in human muscle cells,
Biochem Soc Trans 29, 537-41
Klover PJ, Mooney RA (2004) Hepatocytes: critical for glucose homeostasis, Int J
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Wasserman DH (2009) Four grams of glucose. American Journal of Physiology-
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45 Fettsäuresynthese und β-Oxidation
45.1 Die Struktur der Fettsäuren bestimmt ihre Eigenschaften
Kaneko F et al (1998) Diversity in the fatty-acid conformation and chain packing of
cis-unsaturated lipids, Curr Opin Struct Biol 8, 417-25
Griel AE & Kris-Etherton PM (2006) Beyond saturated fat: The importance of the
dietary fatty acid profile on cardiovascular disease. Nutrition Reviews, 64, 257-262.
45.2 Lipasen hydrolysieren Triacylglycerine zu freien Fettsäuren
Yeaman SJ (2004) Hormone-sensitive lipase – new roles for an old enzyme,
Biochem J 379, 11-22 (PDF)
Cilingiroglu M, Ballantyne C (2004) Endothelial lipase and cholesterol metabolism,
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Zimmermann R, Lass A, Haemmerle G, & Zechner R (2009) Fate of fat: The role of
adipose triglyceride lipase in lipolysis. Biochimica et Biophysica Acta-Molecular and
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45.3 Acylcarnitin ist die Transportform der Fettsäuren
Eaton S (2002) Control of mitochondrial beta-oxidation flux, Prog Lipid Res 41, 197-
239
Ramsay RR, Naismith JH (2003) A snapshot of carnitine acetyltransferase, Trends
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45.4 Die β-Oxidation spaltet sukzessive C2-Einheiten von Fettsäuren ab
Ghisla S (2004) Beta-oxidation of fatty acids. A century of discovery, Eur J Biochem
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45.5 Zwei zusätzliche Enzyme erlauben den Abbau ungesättigter Fettsäuren
Novikov DK et al (1999) Enzymology of beta-oxidation of (poly)unsaturated fatty
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Poirier Y, Antonenkov VD, Glumoff T, & Hiltunen JK (2006) Peroxisomal beta-
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45.6 Bei einem Überangebot an Acetyl-CoA entstehen Ketonkörper
Fukao T et al (2004) Pathways and control of ketone body metabolism: on the fringe
of lipid biochemistry, Prostaglandins Leukot Essent Fatty Acids 70, 243-51
Maalouf M, Rho JM, & Mattson MP (2009) The neuroprotective properties of calorie
restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews, 59, 293-
315. (PDF)
45.7 Die Fettsäuresynthese ist keine einfache Umkehrung der β-Oxidation
Munday MR (2002) Regulation of mammalian acetyl-CoA carboxylase, Biochem Soc
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Smith S et al (2003) Structural and functional organization of the animal fatty acid
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45.8 Fettsäure-Synthase ist ein multifunktionelles Enzym
Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven
enzymes, FASEB J 8, 1248-59 (PDF)
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45.9 Fettsäuren entstehen durch multiple Kondensation von C2-Einheiten
Wakil SJ (1989) Fatty acid synthase, aproficient multifunctional enzyme,
Biochemistry 28, 4523-30
Kremer L, Dover LG, Carrere S, Nampoothiri KM, Lesjean S, Brown AK, Brennan PJ,
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characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from
Mycobacterium tuberculosis. Biochemical Journal, 364, 423-430. (PDF)
45.10 Im Cytosol entstehen längerkettige und ungesättigte Fettsäuren
Ntambi JM, Miyazaki M (2003) Recent insights into stearoyl-CoA desaturase-1, Curr
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Leonard AE et al (2004) Elongation of long-chain fatty acids, Prog Lipid Res 43, 36-
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Tehlivets O, Scheuringer K, & Kohlwein SD (2007) Fatty acid synthesis and
elongation in yeast. Biochimica et Biophysica Acta-Molecular and Cell Biology of
Lipids, 1771, 255-270.
45.11 Arachidonsäure ist die Vorstufe von Prostaglandinen und Thromboxanen
Ruan KH (2004) Advance in understanding the biosynthesis of prostacyclin and
thromboxane A2 in the endoplasmic reticulum membrane via the cyclooxygenase
pathway, Mini Rev Med Chem 4, 639-47
Harizi H, Corcuff JB, & Gualde N (2008) Arachidonic-acid-derived eicosanoids: roles
in biology and immunopathology. Trends in Molecular Medicine, 14, 461-469.
46 Biosynthese von Cholesterin, Steroiden und Membranlipiden
46.1 Cholesterin entsteht durch multiple Kondensation von Acetyl-CoA
Olivier LM, Krisans SK (2000) Peroxisomal protein targeting and identification of
peroxisomal targeting signals in cholesterol biosynthetic enzymes, Biochim Biophys
Acta 1529, 89-102
Santosa S, Varady KA, AbuMweis S, & Jones PJ (2007) Physiological and
therapeutic factors affecting cholesterol metabolism: Does a reciprocal relationship
between cholesterol absorption and synthesis really exist? Life Sciences, 80, 505-
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46.2 Eine komplexe Reaktionsabfolge führt vom Isopentenylpyrophosphat zum Cholesterin
Wang KC, Ohnuma S (2000) Isoprenyl diphosphate synthases, Biochim Biophys
Acta 1529, 33-48
DeBose-Boyd RA (2008) Feedback regulation of cholesterol synthesis: sterol-
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46.3 Lipoproteine steuern Transport und Verwertung von Cholesterin
Kruth HS (2001) Lipoprotein cholesterol and atherosclerosis, Curr Mol Med 1, 633-53
Schaefer EJ (2002) Lipoproteins, nutrition, and heart disease, Am J Clin Nutr 75,
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Davidson WS & Thompson TB (2007) The structure of apolipoprotein A-I in high
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46.4 LDL wird über rezeptorvermittelte Endocytose internalisiert
Schneider WJ, Nimpf J (2003) LDL receptor relatives at the crossroad of endocytosis
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46.5 Störungen der Cholesterinverwertung führen zu Hyperlipidämien
Soutar AK et al (2003) Genetics, clinical phenotype, and molecular cell biology of
autosomal recessive hypercholesterolemia, Arterioscler Thromb Vasc Biol 23, 1963-
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Gotto AM Jr (2003) Treating hypercholesterolemia: looking forward, Clin Cardiol 26(1
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46.6 Gallensäuren und Steroidhormone entstehen aus Cholesterin
Russell DW (2003) The enzymes, regulation, and genetics of bile acid synthesis,
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Espenshade PJ & Hughes AL (2007) Regulation of sterol synthesis in eukaryotes.
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Norlin M & Wikvall K (2007) Enzymes in the conversion of cholesterol into bile acids.
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46.7 Gallensäuren sind natürliche Detergenzien
Thomson AB et al (1993) Lipid absorption: passing through the unstirred layers,
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46.8 Progesteron ist die gemeinsame Vorstufe aller Steroidhormone
Edwards PA, Ericsson J (1999) Sterols and isoprenoids: signaling molecules derived
from the cholesterol biosynthetic pathway, Annu Rev Biochem 68, 157-85
Patel FA, Funder JW, & Challis JRG (2003) Mechanism of cortisol/progesterone
antagonism in the regulation of 15-hydroxyprostaglandin dehydrogenase activity and
113
114
messenger ribonucleic acid levels in human chorion and placental trophoblast cells at
term. Journal of Clinical Endocrinology & Metabolism, 88, 2922-2933. (PDF)
46.9 Phosphatidsäure ist die gemeinsame Vorstufe aller Phosphoglyceride
Vance JE, Vance DE (2004) Phospholipid biosynthesis in mammalian cells, Biochem
Cell Biol 82, 113-28
Kooijman EE & Burger KNJ (2009) Biophysics and function of phosphatidic acid: A
molecular perspective. Biochimica et Biophysica Acta-Molecular and Cell Biology of
Lipids, 1791, 881-888.
Carman GM & Han GS (2009) Phosphatidic Acid Phosphatase, a Key Enzyme in the
Regulation of Lipid Synthesis. Journal of Biological Chemistry, 284, 2593-2597.
(PDF)
46.10 Ceramid ist die Vorstufe aller Sphingolipide
Merrill AH Jr (2002) De novo sphingolipid biosynthesis: a necessary, but dangerous,
pathway, J Biol Chem 277, 25843-6 (PDF)
Hanada K (2003) Serine palmitoyltransferase, a key enzyme of shpingolipid
metabolism, Biochim Biophys Acta 1632, 16-30
Grassme H, Riethmuller J, & Gulbins E (2007) Biological aspects of ceramide-
enriched membrane domains. Progress in Lipid Research, 46, 161-170.
46.11 Ein gestörter Sphingolipidabbau führt zu Lipidspeicherkrankheiten
Butters TD et al (2003) New therapeutics for the treatment of glycosphingolipid
lysosomal storage diseases, Adv Exp Med Biol 535, 219-26
Zhang X, Kiechle FL (2004) eview: Glycosphingolipids in health and disease, Ann
Clin Lab 34, 3-13
Sillence DJ (2007) New insights into glycosphingolipid functions - Storage, lipid rafts,
and translocators. Elsevier Academic Press Inc., San Diego.
47 Abbau von Aminosäuren und Harnstoffzyklus
47.1 Transaminierungen entfernen die α-Aminogruppe der Aminosäuren
Christen P, Mehta PK (2001) From cofactor to enzymes. The molecular evolution of
pyridoxal-5’-phosphate-dependent enzymes, Chem Rec 1, 436-47
Burns KA, Kurian S, & Burke CC (2007) Evaluating patients with mildly elevated
transaminase levels. Clin J Oncol Nurs, 11.
47.2 Der Harnstoffzyklus entsorgt freie Ammoniumionen unter Energieaufwand
Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine
metabolism, Annu Rev Nutr 22, 87-105
Husson A et al (2003) Argininosuccinate synthetase from the urea cycle to the
citrulline-NO cycle, Eur J Biochem 270, 1887-99 (PDF)
Deignan JL, Cederbaum SD, & Grody WW (2008) Contrasting features of urea cycle
disorders in human patients and knockout mouse models. Molecular Genetics and
Metabolism, 93, 7-14. (PDF)
47.3 Das Kohlenstoffgerüst der Aminosäuren gelangt in den Citratzyklus
Owen OE et al (2002) The key role of anaplerosis and cataplerosis for citric acid
cycle function, Biol Chem 277, 30409-12 (PDF)
Newsholme P, Brennan L, Rubi B, & Maechler P (2005) New insights into amino acid
metabolism, beta-cell function and diabetes. Clinical Science, 108, 185-194.
47.4 Hauptprodukt der C2- und C3-Familien sind Acetyl-CoA bzw. Pyruvat
Yudkoff M (1997) Brain metabolism of branched-chain amino acids, Glia 21, 92-8
Layman DK (2002) Role of leucine in protein metabolism during exercise and
recovery, Can J Appl Physiol 27, 646-63
115
116
47.5 Oxalacetat, Succinat und Fumarat sind Intermediate der C4-Familie
Blau N, Erlandsen H (2004) The metabolic and molecular bases of
tetrahydrobiopterinresponsive phenylalanine hydroxylase deficiency, Mol Genet
Metab 82, 101-11
Schnell JR et al (2004) Structure, dynamics, and catalytic function of dihydrofolate
reductase, Annu Rev Biophys Biomol Struct 33, 119-40
Bolstad DB, Bolstad ESD, Wright DL, & Anderson AC (2008) Dihydrofolate reductase
inhibitors: developments in antiparasitic chemotherapy. Expert Opinion on
Therapeutic Patents, 18, 143-157.
47.6 Verzweigtketten-Dehydrogenase baut Intermediate der C4-S-Familie
ab
Banerjee R, Ragsdale SW (2003) The many faces of vitamin B12: catalysis by
cobalamin-dependent enzymes, Annu Rev Biochem 72, 209-47
Harris RA et al (2004) Mechanisms responsible for regulation of branched-chain
amino acid catabolism, Biochem Biophys Res Commun 313, 391-6
Binder S, Knill T, & Schuster J (2007) Branched-chain amino acid metabolism in
higher plants. Physiologia Plantarum, 129, 68-78.
47.7 α-Ketoglutarat ist Sammelpunkt beim Abbau der C5-Familie
Curthoys NP, Watford M (1995) Regulation of glutaminase activity and glutamine
metabolism, Annu Rev Nutr 15, 133-59
Haussinger D & Schliess F (2007) Glutamine metabolism and signaling in the liver.
Frontiers in Bioscience, 12, 371-391.
48 Biosynthese von Aminosäuren und Häm
48.1 Die α-Aminogruppe entstammt molekularem Stickstoff
Suarez I et al (2002) Glutamine synthetase in brain: effect of ammonia, Neurochem
Int 41, 123-42
Stanley CA (2004) Hyperinsulinism/hyperammonemia syndrome: insights into the
regulatory role of glutamate dehydrogenase in ammonia metabolism, Mol Genet
Metab 81 Suppl 1, 45-51
48.2 Das Kohlenstoffgerüst der Aminosäuren stammt aus Intermediaten des Stoffwechsels
Umbarger HE (1978) Amino acid biosynthesis and its regulation, Annu Rev Biochem
47, 532-606
Curien G, Biou V, Mas-Droux C, Robert-Genthon M, Ferrer JL, & Dumas R (2008)
Amino acid biosynthesis: New architectures in allosteric enzymes. Plant Physiology
and Biochemistry, 46, 325-339.
48.3 Einfache Reaktionen liefern acht nichtessenzielle Aminosäuren
Maden BE (2000) Tetrahydrofolate and tetrahydromethanopterin compared:
functionally distinct carriers in C1 metabolism, Biochem J 350, 609-29 (PDF)
Selhub J (2002) Folate, vitamin B12 and vitamin B6 and one carbon metabolism,
Nutr Health Aging 6, 39-42
Ragsdale SW (2008) Catalysis of Methyl Group Transfers Involving Tetrahydrofolate
and B-12. Elsevier Academic Press Inc., San Diego.
48.4 3-Phosphoglycerat ist Vorstufe für Serin, Glycin und Cystein
Fontecave M et al (2004) S-adenosylmethionine: nothing goes to waste, Trends
Biochem Sci 29, 243-9
Stipanuk MH (2004) Sulfur amino acid metabolism: pathways for production and
removal of homocysteine and cysteine, Annu Rev Nutr 24, 539-77
117
118
Wang SC & Frey PA (2007) S-adenosylmethionine as an oxidant: the radical SAM
superfamily. Trends in Biochemical Sciences, 32, 101-110.
48.5 Aminosäuren sind Vorstufen von Hormonen und Neurotransmittern
Barrenetxe J et al (2004) Physiological and metabolic functions of melatonin, Physiol
Biochem 60, 61-72
Grillo MA, Colombatto S (2004) Metabolism and function in animal tissues of
agmatine, a biogenic amine formed from arginine, Amino Acids 26, 3-8
Kvetnansky R, Sabban EL, & Palkovits M (2009) Catecholaminergic Systems in
Stress: Structural and Molecular Genetic Approaches. Physiological Reviews, 89, 535-606. (PDF)
48.6 Porphyrine entstehen aus Glycin und Succinyl-CoA
Fujita H (1997) Molecular mechanism of heme biosynthesis, Tohoku J Exp Med 183,
83-99 (PDF)
Schultz IJ, Chen C, Paw BH, & Hamza I (2010) Iron and porphyrin trafficking in heme
biogenesis. J Biol Chem, 285.
48.7 Der Abbau von Häm erzeugt Bilirubin und Biliverdin
Kapitulnik J (2004) Bilirubin: an endogenous product of heme degradation with both
cytotoxic and cytoprotective properties, Mol Pharmacol 66, 773-9 (PDF)
Shibahara S et al (2002) Heme degradation and human disease: diversity is the soul
of life, Antioxid Redox Signal 4, 593-602
Vitek L & Ostrow JD (2009) Bilirubin Chemistry and Metabolism; Harmful and
Protective Aspects. Current Pharmaceutical Design, 15, 2869-2883.
49 Bereitstellung und Verwertung von Nucleotiden
49.1 Die Neusynthese von Purinnucleotiden läuft über zehn Teilreaktionen
Zalkin H, Dixon JE (1992) De novo purine nucleotide biosynthesis, Prog Nucleic Acid
Res Mol Biol 42, 259-87
Tatibana M et al (1995) Mammalian phosphoribosyl-pyrophosphate synthetase, Adv
Enzyme Regul 35, 229-49
Zimmer HG (1998) Significance of the 5-phosphoribosyl-1-pyrophosphate pool for
cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine,
inosine, and orotic acid in rats, Cardiovasc Drugs Ther 12 Suppl2, 179-87
49.2 Der zweite Teil des Purinringsystems wird schrittweise aufgebaut
Maden BE (2000) Tetrahydrofolate and terahydromethanopterin compared:
functionally distinct carriers in C1 metabolism, Biochem J 350, 609-29 (PDF)
Ashihara H, Sano H, & Crozier A (2008) Caffeine and related purine alkaloids:
Biosynthesis, catabolism, function and genetic engineering. Phytochemistry, 69, 841-
856.
49.3 Die Biosynthese von Purinnucleotiden wird engmaschig kontrolliert
Moriwaki Y et al (1999) Enzymes involved in purine metabolism – a review of
histochemical localization and functional implications, Histol Histopathol 14, 1321-40
Downie MJ, Kirk K, & Ben Mamoun C (2008) Purine salvage pathways in the
intraerythrocytic malaria parasite Plasmodium falciparum. Eukaryotic Cell, 7, 1231-
1237. (PDF)
49.4 Carbamoylphosphat, Aspartat und PRPP sind Bausteine bei der Pyrimidinbiosynthese
Evans DR, Guy HI (2004) Mammalian pyrimidine biosynthesis: fresh insights into an
ancient pathway, J Biol Chem 279, 33035-8 (PDF)
119
120
Zrenner R, Stitt M, Sonnewald U, & Boldt R (2006) Pyrimidine and purine
biosynthesis and degradation in plants. Annual Review of Plant Biology, 57, 805-836.
49.5 Nucleosidtriphosphate entstehen unter Verbrauch von ATP
Ishikawa N et al (2003) Molecular evolution of nucleoside diphosphate kinase genes:
conserved core structures and multiple-layered regulatory regions, J Bioenerg
Biomembr 35, 5-6
Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: Important
modulators of purinergic signalling cascade. Biochimica et Biophysica Acta-Molecular
Cell Research, 1783, 673-694.
49.6 Desoxyribonucleotide entstehen aus Nucleosiddiphosphaten
Eklund H et al (2001) Structure and function of the radical enzyme ribonucleotide
reductase, Prog Biophys Mol Biol 77, 177-268
Stubbe J et al (2003) Radical initiation in the class I ribonucleotide reductase: long-
range proton-coupled electron transfer?, Chem Rev 103, 2167-201
Herrick J & Sclavi B (2007) Ribonucleotide reductase and the regulation of DNA
replication: an old story and an ancient heritage. Molecular Microbiology, 63, 22-34.
49.7 Fluoruracil ist ein irreversibler Hemmstoff der Thymidylat-Synthase
el Kouni MH (2003) Potential chemotherapeutic targets in the purine metabolism of
parasites, Pharmacol Ther 99, 283-309
van Kuilenburg AB et al (2004) Pyrimidine degradation defects and severe 5-
fluorouracil toxicity, Nucleosides Nucleotides Nucleic Acids 23, 1371-5
49.8 Harnstoff und Harnsäure sind die Hauptabbauprodukte der Nucleotide
van Gennip AH, van Kuilenburg AB (2000) Defects of pyrimidine degradation: clinical,
molecular and diagnostic aspects, Adv Exp Med Biol 486, 233-41
Beck H, Dobritzsch D, & Piskur J (2008) Saccharomyces kluyveri as a model
organism to study pyrimidine degradation. Fems Yeast Research, 8, 1209-1213.
50 Koordination und Integration des Stoffwechsels
50.1 Die metabolischen Homöostase jeder Einzelzelle wird bedarfsgerecht eingestellt
Lage R, Dieguez C, Vidal-Puig A, & Lopez M (2008) AMPK: a metabolic gauge
regulating whole-body energy homeostasis. Trends in Molecular Medicine, 14, 539-
549.
Wheatcroft SB & Kearney MT (2009) IGF-dependent and IGF-independent actions of
IGF-binding protein-1 and-2: implications for metabolic homeostasis. Trends in
Endocrinology and Metabolism, 20, 153-162.
50.2 Glucose-6-phosphat, Pyruvat und Acetyl-CoA markieren metabolische Knotenpunkte
Cappellini MD & Fiorelli G (2008) Gluclose-6-phosphate dehydrogenase deficiency.
Lancet, 371, 64-74.
Roche TE & Hiromasa Y (2007) Pyruvate dehydrogenase kinase regulatory
mechanisms and inhibition in treating diabetes, heart ischemia, and cancer. Cellular
and Molecular Life Sciences, 64, 830-849.
50.3 Transportvorgänge tragen zur Aufrechterhaltung der metabolischen Homöostase bei
Kellett GL, Brot-Laroche E, Mace OJ, & Leturque A (2008) Sugar absorption in the
intestine: The role of GLUT2. Annual Review of Nutrition, 28, 35-54.
Wu IC, Ohsawa I, Fuku N, & Tanaka M (2010) Metabolic analysis of 13C-labeled
pyruvate for noninvasive assessment of mitochondrial function. Ann N Y Acad Sci,
1201.
121
50.4 Die Koordination des Stoffwechsels beruht auf einer Arbeitsteilung zwischen Organen
Kraemer FB & Shen WJ (2006) Hormone-sensitive lipase knockouts. Nutrition &
Metabolism, 3. (PDF)
Maalouf M, Rho JM, & Mattson MP (2009) The neuroprotective properties of calorie
restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews, 59, 293-
315. (PDF)
50.5 Hormone orchestrieren den Gesamtstoffwechsel eines Organismus
Newsholme EA, Dimitriadis G (2001) Integration of biochemical and physiologic
effects of insulin on glucose metabolism, Exp Clin Endocrinol Diabetes 109 Suppl 2,
122-34
Silva JE (2006) Thermogenic mechanisms and their hormonal regulation.
Physiological Reviews, 86, 435-464. (PDF)
50.6 Glucose ist die wichtigste Regelgröße bei Nahrungsaufnahme und Hunger
Herman MA & Kahn BB (2006) Glucose transport and sensing in the maintenance of
glucose homeostasis and metabolic harmony. Journal of Clinical Investigation, 116,
1767-1775. (PDF)
Airley RE & Mobasheri A (2007) Hypoxic regulation of glucose transport, anaerobic
metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer
therapeutics. Chemotherapy, 53, 233-256.
Bansal P & Wang QH (2008) Insulin as a physiological modulator of glucagon
secretion. American Journal of Physiology-Endocrinology and Metabolism, 295,
E751-E761. (PDF)
50.7 Der Organismus antizipiert Situationen erhöhten Energiebedarfs durch gezielte Stoffwechselanpassungen
Febbraio MA (2001) Alterations in energy metabolism during exercise and heat
stress, Sports Med 31, 47-59
122
123
Seematter G et al (2004) Relationship between stress, inflammation and metabolism,
Curr Opin Clin Nutr Metab Care 7, 169-73
Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, & Mikhailidis DP (2009) The
Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis. Journal of
Clinical Endocrinology & Metabolism, 94, 2692-2701. (PDF)
50.8 Langfristige Anpassung des Energiestoffwechsels
Fruhbeck G (2006) Intracellular signalling pathways activated by leptin. Biochemical
Journal, 393, 7-20. (PDF)
Soares JB & Leite-Moreira AF (2008) Ghrelin, des-acyl ghrelin and obestatin: Three
pieces of the same puzzle. Peptides, 29, 1255-1270.
50.9 Störungen des Glucosestoffwechsels führen zu schwerwiegenden Erkrankungen
Khaw KT & Wareham N (2006) Glycated hemoglobin as a marker of cardiovascular
risk. Current Opinion in Lipidology, 17, 637-643.
Hipolito L, Sanchez MJ, Polache A, & Granero L (2007) Brain metabolism of ethanol
and alcoholism: An update. Current Drug Metabolism, 8, 716-727.
Barsotti A, Giannoni A, Di Napoli P, & Emdin M (2009) Energy Metabolism in the
Normal and in the Diabetic Heart. Current Pharmaceutical Design, 15, 836-840.
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