Purine and Pyrimidine Metabolism

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Nucleotide Synthesis:

• Two ways: de novo and salvage pathways.

de novo: occurs in liver; purines and pyramidines are synthesized from smaller precursors.

• Salvage pathways: purines and pyramidines converted into nucleotides directly by salvage enzymes.

Lesch-Nyhan:

• Absent salvage enzyme (HPRT).

• Orange crystals in diapers of babies.

• Self mutilation.

• Purines are not salvaged, and excreted, causing synthesis of more purines.

• Urate accumulation causes gouty arthritis and urate nephropathy.

Pyramidine Synthesis:

de novo in cytoplasm from aspartate, CO2, and glutamine.

• UMP formed in the end, and converted to dTMP.

• Important enzymes: ribonucleotide reductase, thymidylate synthase, and dihydrofolate reductase.

Orotic Aciduria:

• Defective orotic acid phosphoribosyltransferase or OMP.

• Orotic acid cannot be converted to UMP; excreted in urine.

• Megaloblastic anemia.

• Uridine salvaged to UMP, which inhibits carbamoyl phosphate synthase-2, preventing orotic acid formation.

• Treatment: uridine.

Purine Synthesis:

de novo with PRPP.

• Important enzyme: PRPP amidotransferase, which catalyzes first and rate-limiting reaction.

• PRPP amidotransferase inhibited by AMP, GMP, and IMP.

Purine Catabolism:

• 90% purines are recycled and 10% are converted to uric acid and excreted.

• Increased purine catabolism causes hyperuricemia and gout.

Adenosine Deaminase Deficiency:

• Produces SCID.

• dATP accumulates in RBCs, indirectly inhibiting DNA systhesis.

Hyperuricemia and Gout:

• Uric acid overproduction.

• AMP cannot be phosphorylated to ADP and ATP; AMP converted to uric acid.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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