Effect of Phenyl and Phenolic Acids on Mevalonate‐5‐phosphate Kinase and Mevalonate‐5‐pyrophosphate Decarboxylase of the Rat Brain

Phenyl and phenolic acids are known to inhibit metabolism of mevalonate in rat brain. The site of inhibition has been found to be mevalonate‐5‐pyrophosphate decarboxylase. Phenolic acids also inhibited mevalonate‐5‐phosphate kinase on preincubation. The kinetics showed that p‐coumaric acid and isoferulic acid were competing with substrates, mevalonate‐5‐phosphate or mevalonate‐5‐pyre phosphate, whereas others showed an uncompetitive type of inhibition. Chlorophenoxyisobutyrate, a hypocholesterolaemic drug, had no effect on these enzymes. An improved method for the synthesis of mevalonate‐5‐phosphate and mevalonate‐5‐pyrophosphate, labeled at carbon‐1, is described.