The utilization of L- and D-phenylalanine by the rat.

An investigation of the oxidation of phenylalanine has been undertaken in this laboratory in connection with studies of the hereditary defect phenylketonuria (phenylpyruvic oligophrenia), in which the oxidation does not occur in the normal manner. The biochemical defect is accompanied by a profound impairment of mental functioning (2, 3). A knowledge of the details of the oxidation might lead to information as to whether the specific oxidative process or an intermediate involved in the oxidation is concerned with normal mental functioning, or whether a failure in the oxidation results in the accumulation of a product which is detrimental to nerve tissue. The mechanism by which phenylalanine is oxidized is unknown. Conclusive proof that it is oxidized to tyrosine has been afforded by several lines of investigation (4-6), and it appears likely that this is the major pathway by which phenylalanine normally is catabolized in the mammalian organism. Recently, reports have been made of the oxidation of phenylalanine by various preparations in vitro (7-9), but none of these experiments clarifies the process by which phenylalanine is activated in the para position, the nature of the immediate oxidizing agent, or the manner in which this substance is formed. Nutritional studies with the young white rat have been carried out in an initial approach to this problem. Experiments with some oxidized derivatives of phenylalanine and an attempt to use fluorine-substituted phenylalanines as inhibitors of the oxidation in the intact animal have been reported (10, 11). This paper presents and discusses results obtained in an examination of the nutritional availability of Land n-phenylalanine and phenylpyruvic acid in growth experiments designed to give information on the over-all problem.