Pirimidinas_2025_Curso Ácidos nucleicos. Cinvestav
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Curso biomoléculas 2. DNA structure: Síntesis de pirimidinas. Maestría en Genética y Biología Molecular. Cinvestav. Dr. Luis Alvarez
Pirimidinas_2025_Curso Ácidos nucleicos. Cinvestav
- 9. Atom assembly of pyrimidine ring
- 11. Interconversion of Nucleotides The nucleoside monophosphates are the forms synthesized de novo. The triphosphates are the most commonly used forms. The monophosphates are converted to the di- and tri-phosphates by the sequential activities of nucleoside monophosphate kinases and nucleoside diphosphate kinase. The reactions are reversible, so the nucleoside mono-, di- and triphosphateforms are in equilibrium. Nucleoside monophosphate kinases: convert nucleoside monophosphates to diphosphates, using ATP as phosphate donor nucleoside monophosphate kinases show substrate specificity (different enzymes phosphorylate AMP, GMP, pyrimidines and deoxynucleotides) Adenylate kinase: AMP + ATP 2 ADP Thymidylate kinase: TMP + ATP TDP + ADP Nucleoside diphosphate kinase: converts nucleoside diphosphates to triphosphates, using ATP as phosphate donor nucleoside diphosphate kinase (NDK) has broad specificity (one enzyme can phosphorylate purine and pyrimidine ribo-and deoxyribonucletides) examples: GDP + ATP GTP + ADP dGDP + ATP dGTP + ADP UDP + ATP UTP + ADP
- 17. Summary
- 19. dTMP Synthesis
- 25. OROTACIDURIA inherited disorder of pyrimidine synthesis caused by a deficiency of the enzyme of orotate-phosphoribosyltransferase and decarboxylase. Symptoms: –excess of orotic acid and its excretion with urine (1.0-1.5 g) -mental and physical retardation -megaloblastic anemia
- 26. – Treatment: patients are fed uridine U UMP UDP UTP UTP inhibits carbamoyl phosphate synthase II, preventing the biosynthesis and accumulation of orotic acid O OH OH CH2 O P O P O -O -O O- - O3PO O C NH O HN C OOC C H C O PPi Orotate 5-phosphoribosyl-1-pyrophosphate (PRPP)