Inhibition of chick brain cholesterogenic enzymes by phenyl and phenolic derivatives of phenylalanine.

Phenylalanine and its phenyl metabolites produced a clear inhibition of chick brain mevalonate 5-pyrophosphate decarboxylase, while mevalonate kinase and mevalonate 5-phosphate kinase were not significantly affected. Phenolic derivatives produced a similar or higher inhibition than that found in the presence of phenyl metabolites. The inhibition was progressive with increasing concentrations of inhibitors (1.25-5.00 mM). Phenylpyruvate and p-hydroxyphenyl-lactate were the most potent inhibitors of decarboxylase activity. Simultaneous supplementation of each metabolite at 0.25 mM concentration produced a considerable inhibition of brain decarboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase. At our knowledge this is the first report on the in vitro inhibition of both brain regulatory enzymes of cholesterogenesis in phenylketonuric-like conditions.