Pyrimidine metabolism

Click here to load reader

Embed Size (px)

Transcript of Pyrimidine metabolism

  1. 1. PRPP Purine nucleotides Pyrimidine nucleotides Denovo and Salvage pathways AlanineUric acid Degradative pathways
  2. 2. Shorter pathway Base is made first, then attached to ribose-P (unlike purine biosynthesis) Only 2 precursors (aspartate and glutamate + HCO3 - ) contribute to the 6-membered ring The product is OMP (orotydilate)
  3. 3. N1, C4, C5, C6 : Aspartate C2 : HCO3- N3 : Glutamine amide Nitrogen
  4. 4. UMP + ATP UDP + ADP UDP + ATP UTP + ADP nucleoside diphosphate kinase CTP synthase (cytidylate synthetase) N N O H O Ribose 3 phosphate N NO Ribose 3 phosphate NH2 glutamine + ATP Glutamate + ADP +Pi CTPUTP
  5. 5. Differs between bacteria and animals Bacteria regulation at ATCase rxn Animals regulation at carbamoyl phosphate synthetase II UDP and UTP inhibit enzyme; ATP and PRPP activate it UMP and CMP competitively inhibit OMP Decarboxylase *Purine synthesis inhibited by ADP and GDP at PRPP synthetase step, controlling level of PRPP also regulates pyrimidines
  6. 6. CMP and UMP degraded to bases similarly to purines Dephosphorylation Deamination Glycosidic bond cleavage
  7. 7. Catabolism of Pyrimidines
  8. 8. Caused by defect in Orotate phosphoribosyl transferase and OMP Decarboxylase Increased excretion of orotic acid in urine Symptoms: retarded growth; severe anemia Only known inherited defect in this pathway Treat with uridine/cytidine HOW DOES URIDINE AND CYTIDINE ADMINISTRATION WORK TO TREAT OROTIC ACIDURIA?