Glycolysis in the brain and liver of rats with experimentally induced phenylketonuria.

The genetically-linked deficiency in the activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) leads to a marked accumulation of L-phenylalanine (L-Phe) and some of its metabolic products, namely phenylpyruvate, phenyl-lactate and o-hydroxyphenylacetate, in the blood and tissues of patients with uncontrolled phenylketonuria (PKU). In order to explain the biochemical mechanisms by which the accumulation of L-Phe and/or its metabolites causes mental retardation in PKU, several hypotheses have been suggested. Weber et ~2. (1) demonstrated that either L-Phe or phenylpyruvate inhibited competitively in dtro the brain pyruvate kinase (PK) (EC 2.7.1.40) and hexokinase (HK) (EC 2.7.1.1.). In this paper we report the in viva effects of high concentrations of LPhe on the levels of glycolytic intermediates in brain and liver of rats with experimentally induced phenylketonuria. The effect of L-Phe on the PK activity in rat liver has been also investigated.