INHIBITION BY BARBITURIC-ACID AND ITS DERIVATIVES OF ENZYMES IN RAT-BRAIN WHICH PARTICIPATE IN SYNTHESIS OF PYRIMIDINE RIBOTIDES

Barbituric acid competitively inhibits dihydro-orotate dehydrogenase, uridine phosphorylase, and (directly or indirectly) orotate phosphoribosyltransferase. In addition, the ribotide of barbituric acid, 6-hydroxyuridine-5′-monophosphate, inhibits uridine monophosphate kinase and is a powerful competitive inhibitor of orotidylate decarboxylase-the final enzyme in the sequence for the de novo synthesis of pyrimidine ribotides. Barbituric acid itself causes marked competitive inhibition of decarboxylase activity provided the reaction mixture contains 5-phosphoribosyl-1-pyrophosphate (PRPP). Another barbituric acid derivative, phenobarbital, is a weak non-competitive inhibitor (in the presence of PRPP) of the decarboxylase. One convulsant barbiturate, DMBB [5-(1,3-dimethylbutyl)-5-ethyl-barbituric acid], and bemegride-a stimulant structurally resembling the barbiturates-were found to inhibit rat brain uridine phosphorylase activity, and this same enzyme was also inhibited by isobarbituric acid. © 1978.