Diminished Phenylketonuria in Phenylpyruvic Oligophrenia After Administration of L-Glutamine, L-Glutamate or L-Asparagine1

It is well known that patients with phenylpyruvic oligophrenia excrete large amounts of phenylpyruvic acid, phenyllactic acid, and phenylalanine in the urine, and that they also exhibit an unusually high blood level of phenylalanine ( 1-4). That such patients also exhibit a markedly reduced capacity to convert phenylalanine to tyrosine was indicated by several investigations (2, 5, 6) and was proven conclusively by isotopic study (7). It has been suggested that failure to catalyze this reaction is the basic metabolic defect in this disorder (6, 7). According to this interpretation, phenylalanine accumulates, and is converted to phenylpyruvic acid and other products in greater than normal quantities. The finding of abnormally high concentrations of phenylacetylglutamine in the urine of patients with phenylpyruvic oligophrenia (8, 9) is also consistent with the increased accumulation of phenylalanine, with its conversion to phenylpyruvic acid, and transformation of the latter compound to phenylacetic acid. In man the latter compound is excreted in the urine as phenylacetylglutamine (10-12). It is reasonable to assume that the chemical defect is responsible in some way for the mental retardation of these patients; such an interpretation gains support from the observation that some patients appear to show improvement when the dietary phenylalanine intake is restricted (13-16). It seems probable that the conversion of phenylalanine to phenylpyruvic acid takes place by transamination; this mechanism has been shown to be responsible for the analogous conversion of tyrosine to p-hydroxyphenylpyruvic acid (17-19).