Studies in alcaptonuria

Abstract

Homogentisic acid has been isolated from the urine of rats fed a diet deficient in methionine and cystine and containing only relatively small amts. of tyrosine and phenylalanine. If cystine was added to such a diet, no alcaptonuria occurred unless the tyrosine intake was also raised. When large amts. of tyrosine were administered, some />-hydroxyphenyl-pyruvic acid was also excreted. Alcaptonuria was also produced if tyrosine was added to a protein-deficient diet. The excretion of homogentisic acid occurring under these conditions was not affected by the admn. of cystine or methionine. The threshold of the intake of phenylalanine and tyrosine necessary to produce alcaptonuria was significantly reduced by a deficiency of tryptophan and, to a lesser extent, by a lack of lysine. It is suggested that any deficiency of an essential amino-acid may impair the capacity of the organism to metabolize tyrosine and phenylalanine in a normal manner. No hepatic lesions were found in any of the animals. Possible reasons for such negative findings are discussed.