BCH4024 - McKenna Lecture 46

BCH4024 - McKenna Lecture 46 - BIOSYNTHESIS AND DEGRADATION...

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1 BIOSYNTHESIS AND DEGRADATION OF NUCLEOTIDES PURINE AND PYRIMIDINE METABOLISM A. INTRODUCTION Purines and pyrimidines participate in many biochemical reactions. 1. Nucleoside triphosphates are activated precursors in DNA replication and synthesis . 2. ATP : UNIVERSAL ENERGY CURRENCY IN ALL CELLS; GTP also used. 3. Adenine nucleotides are components of 3 major coenzymes: NAD + FAD COA 4. Nucleotide derivatives are activated intermediates in many biosyntheses pathways Ex: UDP - GLUCOSE è GLYCOGEN 5. Nucleotides are metabolic regulators Ex: cAMP ... 2 nd messenger in many hormone actions 6. Critical reactions in pu and py biosynthesis are targets for cancer chemotherapy and viral disease treatment . NUCLEOTIDE METABOLISM SALVAGE DE NOVO METABOLIC PATHWAYS SYNTHESIS PRODUCTS RIBOSE, AMINO ACIDS, SOURCES OF -CO 2 AND -NH 2 RIBONUCLEOSIDES REGULATORY MOLECULES COENZYMES BASES RIBONUCLEOTIDES RNA OTHER INTERMEDIATES DEOXYRIBONUCLEOSIDES DEOXYRIBONUCLEOTIDES DNA 3 routes to make NTs
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2 NUCLEOSIDES AND NUCLEOTIDES H Phosphate dAdenosine dAdenylic acid (dAMP) Adenine Deoxyribose Glycosidic bond Deoxyadenosine 5’-monophosphate (dAMP) dATP Deoxythmidine 5’-monophosphate (dTMP) dTTP Deoxyguanosine 5’-monophosphate (dGMP) dGTP Deoxycytidine 5’-monophosphate (dCMP) dCTP De novo synthesis proceeds via triphosphate intermediates THE BUILDING BLOCKS De Novo Pathway for Nucleotide Metabolism NDP Kinase Ribonucleotide Reductase - requires NADPH -also at RR 1 - NDP kinase 2- dUTPase (-Ppi) 3-Thymidylate Synthase Base specific kinases Only route to Thymine nucleotides Only Py NT 1 2 3 RR +NH 2
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3 B. CENTRAL ROLE OF PRPP Ribose phosphate pyrophosphate 1. De Novo synthesis a. Purine ring assembled on PRPP. b.
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This note was uploaded on 03/15/2010 for the course BCH 4024 taught by Professor Allison during the Spring '08 term at University of Florida.

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BCH4024 - McKenna Lecture 46 - BIOSYNTHESIS AND DEGRADATION...

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