Biosynthesis and Degradation of Pyrimidines
Start with the big picture
In de novo synthesis, the pyrimidine ring is assembled before it is joined to PRPP, producing OMP and then UMP. CPS II is the rate-limiting enzyme: PRPP activates it, while UTP inhibits it. UMP supplies UDP and UTP, and CTP synthetase converts UTP to CTP. Further reactions generate deoxyribonucleotides and dTMP; these steps involve targets of drugs such as hydroxyurea and 5-FU. Salvage pathways recycle nucleosides and support activation of some antiviral drugs. The topic also compares orotic aciduria with ornithine transcarbamylase deficiency and describes pyrimidine breakdown products. Because pyrimidine catabolites are water-soluble, their degradation does not cause gout-like crystal deposition.
What you'll learn
- Outline the order of de novo pyrimidine synthesis and identify the first nucleotide formed.
- Explain CPS II regulation and the conversion of UMP into UTP and CTP.
- Identify key steps in deoxyribonucleotide and thymidylate synthesis and their drug targets.
- Describe pyrimidine salvage and distinguish orotic aciduria from ornithine transcarbamylase deficiency.
- Summarize pyrimidine degradation products and their clinical relevance.
Continue your study
Work through the complete notes and reinforce the topic with the study tools available in the full lesson.
