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Virtually all cells are capable of synthesizing purine and pyrimidine nucleotides. These compounds then serve as essential intermediates in metabolism and as the building blocks for DNA and RNA synthesis. In this chapter you will learn: How do cells synthesize purines and pyrimidines? | Chapter 27 The Synthesis and Degradation of Nucleotides to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline 27.1 Nucleotide Biosynthesis 27.2 The Biosynthesis of Purines 27.3 Purine Salvage 27.4 Purine Degradation 27.5 Biosynthesis of Pyrimidines 27.6 Pyrimidine Degradation 27.7 Deoxyribonucleotide Biosynthesis 27.8 Synthesis of Thymine Nucleotides 27.1 Nucleotide Biosynthesis Nearly all organisms synthesize purines and pyrimidines "de novo" Many organisms also "salvage" purines and pyrimidines from diet and degradative pathways Ribose generates energy, but purine and pyrimidine rings do not Nucleotide synthesis pathways are good targets for anti-cancer/antibacterial strategies 27.2 Biosynthesis of Purines John Buchanan (1948) "traced" the sources of all nine atoms of purine ring N-1: aspartic acid N-3, N-9: glutamine C-4, C-5, N-7: glycine C-6: CO2 C-2, C-8: THF - one carbon units Inosine-5'-P Biosynthesis The purine ring is built on a ribose-5-P foundation First step: ribose-5-P must be activated - by PPi PRPP is limiting substance for purine synthesis But PRPP is a branch point so next step is the committed step - Gln PRPP amidotransferase Note that second step changes C-1 configuration G- and A-nucleotides inhibit this step - but at distinct sites! Azaserine - Gln analog - inhibitor/anti-tumor Steps 3-5 Step 3: Glycine carboxyl condenses with amine Glycine carboxyl activated by -P from ATP Amine attacks glycine carboxyl Step 4: Formyl group of N10-formyl-THF is transferred to free amino group of GAR Step 5: C-4 carbonyl forms a P-ester from ATP and active NH3 attacks C-4 to form imine Steps 6-8 Closure of the first ring, carboxylation and attack by aspartate Step 6: Similar in some ways to step 5. ATP activates the formyl group by . | Chapter 27 The Synthesis and Degradation of Nucleotides to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline 27.1 Nucleotide Biosynthesis 27.2 The Biosynthesis of Purines 27.3 Purine Salvage 27.4 Purine Degradation 27.5 Biosynthesis of Pyrimidines 27.6 Pyrimidine Degradation 27.7 Deoxyribonucleotide Biosynthesis 27.8 Synthesis of Thymine Nucleotides 27.1 Nucleotide Biosynthesis Nearly all organisms synthesize purines and pyrimidines "de novo" Many organisms also "salvage" purines and pyrimidines from diet and degradative pathways Ribose generates energy, but purine and pyrimidine rings do not Nucleotide synthesis pathways are good targets for anti-cancer/antibacterial strategies 27.2 Biosynthesis of Purines John Buchanan (1948) "traced" the sources of all .