Nucleotide Metabolism Flashcards
Cause of Gout?
Accumulation of purine catabolic product. Uric acid. Mostly big toe joint. ADA deficiency. Chronic treated by allopurinol
Purine numbering system
Counterclockwise, N-9 attached to sugar
Pyrimidine C numbering system
Clockwise, sugar bound to N1
Ribose5p and deoxyribose5p are produced by what?
Pentose phosphate pathway
Are nucleotides ingested in diet used in metabolism?
No, usually excreted
How are purines and pyrimidines made?
De Novo and Salvage.
Purines synthesized directly on PRPP, pyrimidines pre made and attached. De Novo needs ATP, in liver.
What is the rate limiting step of nucleotide anabolism, and what enzyme is needed?
R5P and ATP to AMP and PRPP. Enzyme is PRPP synthetase
How is PRPP committed to purine biosynthesis?
By PRPP amidotransferase. Adds amine and loses 2p.
When is glutamine used in purine biosynthesis?
Twice, step 2 and 5.
Result of initial steps or purine synthesis?
Inosine monophosphate, with hypoxanthine as base. Branch point for synthesis of AMP and GMP
Steps for formation of adenylate from IMP?
Catalyze by adenylsuccinate synthetase. Aspartate added to c6 carbon. Needs GTP
Steps for formation of guanylate from IMP?
Amine from glutamine added at c2 carbon. Catalyzed by GMP synthase. Activated by AMP attachment.
Regulation of purine formation?
ATP needed to make GMP, and GTP needed to make AMP. Prevents an imbalance from forming
AMP+ATP=2ADP
What enzyme does this?
Adenylate kinase
GMP+ATP=GDP+ADP
What enzyme does this?
Guanylate kinase
XDP+ATP=XTP+ADP
What enzyme does this?
Nucleotide diphosphate kinase
Feedback regulation for purine synthesis?
First two steps inhibited by products. Step one inhibited by DP, two by MP.
Pyrimidine biosynthesis steps?
Two things attached to make orotate, attached to PPRP to make OMP. Processed to make UMP. Glutamine makes CTP from UTP.
How is TTP made?
From deoxyUMP only. Which is made by ribonucleotide reductase. Then thymidine synthase
What is ribonucleotide reductase inhibited by?
Its products, such as dATP.
Salvage reactions for nucleotide metabolism?
Attach free bases to PRPP. Most important enzyme is HGRPT, which attaches base to sugar.
Nucleotide degradation?
Purines degraded to uric acid. Usually close to solubility limit, so increase is very bad
ADA deficiency
ADA converts adenylate to inosylate. Alternative pathways not found for dAdenylate, so rapid cell division affected. Immunodeficiency
Hyperuricemia causes
Increase in purine biosynthesis or degradation. Decreased excretion. Increased PRPP synthesis, or decreased HGRPT
