| Synthesis of purine nucleotides, ATP, and guanosine triphosphate (GTP) from IMP
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IMP is the precursor of other purine nucleotides; it does not accumulate significantly within the cell. As shown in Figure 29.3, IMP serves as the starting material for both adenosine and guanosine monophosphate (AMP and GMP). Two enzymatic reactions are required to convert the ring system of IMP into that of AMP. In reactions similar to those in steps 8 and 9 for addition of the N6 purine nitrogen to CAIR, aspartate is added at C-6 of IMP to form the adenylosuccinate intermediate by adenylosuccinate synthetase. Adenylosuccinate lyase then catalyzes hydrolysis of adenylosuccinate, yielding fumarate and AMP.
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| The formation of GMP from IMP is also a two-step process. The C-2 carbon is oxidized by IMP dehydrogenase by sequential hydration and oxidation reactions to yield xanthine monophosphate (XMP). XMP is then converted into GMP by GMP synthetase, using glutamine as the nitrogen donor (Fig. 29.3).
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| Figure 29.2 Portions of the purine biosynthetic pathway. Enzymes for indicated steps: (1) PRPP synthetase; (2) amidophosphoribosyl-transferase; (3) GAR synthetase; (4) GAR transformylase; (5) FGAM synthetase; (6) AIR synthetase; (7) AIR carboxylase; (8) SACAIR synthetase; (9) adenylosuccinate lyase; (10) AICAR transformylase; (11) IMP synthase. |
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| Figure 29.3 The conversion of IMP into AMP and GMP. Two enzymatic reactions are needed for each branch of the pathway. |
| Adenylate kinase and guanylate kinase use ATP to synthesize the nucleotide diphosphates from the nucleotide monophosphates. Finally, a single enzyme, termed nucleotide diphosphokinase, converts diphosphonucleotides into triphosphonucleotides. This enzyme has activity towards all nucleotide diphosphates, regardless of the base or sugar.
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