Studies on Oligophrenia Phenylpyruvica I. Microbiological Determination of L- and D-phenylalanine and of Phenyllactic Acid* by Blanche A. Prescott, Ernest Borek,

The disease oligophrenia phenylpyruvica (phenylketonuria) presents a unique opportunity for the study of the relation of amino acid metabolism to the function of the central nervous system. In this inborn error of metabolism, which is inherited as a Mendelian recessive character, mental deficiency is accompanied by faulty phenylalanine metabolism. The metabolic disturbance was first recognized by the urinary excretion of large amounts of phenylpyruvic acid (3). It was soon recognized, however, that the voiding of the keto acid is accompanied by an abnormally high excretion of phenylalanine and phenyllactic acid as well. The source of the excreted amino acid and its metabolic derivatives is probably the high concentration of phenylalanine in the blood of these subjects. Two explanations have been proposed for the biochemical mechanism of the metabolic error. Fiilling and his collaborators suggested the metabolic accumulation of n-phenylalanine and its subsequent deamination in the kidney as the source of the excreted keto acid, but they were unable to demonstrate the presence of the unnatural antipode in body fluids (4). Jervis has presented strong evidence that the metabolic disturbance resides in an inability to hydroxylate the aromatic ring (5). At present it is not known whether the inability to hydroxylate is complete, because of the total lack of a specific enzyme system, or whether only parahydroxylation is affected. The impaired ability of many patients with this disease to form melanin points to a more extensive disturbance of the metabolism of the aromatic nucleus (6). Furthermore, the lack of quantitative data on the occurrence of the various metabolic products makes a correlation between the degree of mental impairment and the extent of the metabolic deficiency impossible. Microbiological methods, because of their sensitivity and specificity, seemed to offer a valuable tool for the study of this metabolic disturbance. We report here a method for the microbiological determination of each isomer of phenylalanine and of m-phenyllactic acid and its application to