Download - Pyrimidine metabolism
PRPP
Purine nucleotides Pyrimidine nucleotides
Denovo and Salvage pathways
β AlanineUric acid
Degradative pathways
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)
N1, C4, C5, C6 : AspartateC2 : HCO3-N3 : Glutamine amide Nitrogen
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
NH2glutamine +ATP
Glutamate +ADP +Pi
CTPUTP
Differs between bacteria and animalsBacteria – regulation at ATCase rxn
Animals – regulation at carbamoyl phosphate synthetase IIUDP and UTP inhibit enzyme; ATP and PRPP
activate itUMP and CMP competitively inhibit OMP
Decarboxylase*Purine synthesis inhibited by ADP and GDP
atPRPP synthetase step, controlling level of
PRPP also regulates pyrimidines
CMP and UMP degraded to bases similarly to purines Dephosphorylation Deamination Glycosidic bond cleavage
Catabolism of Pyrimidines
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?