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aminoglycan bond formed • analogous to pyrimidine salvage Pyrimidine Biosynthesis • orotidylate decarboxylase • catalyzes synthesis of UMP • very efficient enzyme • uridylate kinase • nucleoside monophosphate kinase specific for UMP • nucleoside diphosphate kinase • generic enzyme for (d)NDP’s • cytidylate synthetase • an amidotransferase • UTP is aminated using glutamine • carbonyl group is activated with ATP to form acyl phosphate intermediate Cytidine 5’-triphosphate (CTP) Pyrimidine Biosynthesis Enzyme Complexes • Eukaryotes have a multifunctional protein with the first 3 enzymes in pyrimidine biosynthetic pathway C carbamoyl phosphate synthetase II A aspartate transcarbamoylase D dihydroorotase • CAD has 3 identical polypeptides (Mr 230,000) each with sites for all 3 reactions Regulation of Pyrimidine Biosynthesis • Feedback inhibition of 1st step aspartate transcarbamoylase (ATCase) by CTP • Bacterial ATCase has: • 6 catalytic subunits • 6 regulatory subunits • Allosteric inhibition: • 2 conformations of ATCase: active ↔ inactive • binding of CTP to regulatory subunits shifts conformation active → inactive • ATP reverses effect of CTP Activation of Nucleotides • Nucleoside monophosphate kinases • specific enzyme for each base (e.g

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583, 377–382 [DOI] [PubMed] [Google Scholar] 265.Yang G., Yang W., Wu L., Wang R