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?