The Excretion of Homogentisic Acid and Other Tyrosine Metabolites by the Vitamin C-Deficient Guinea Pig

In the course of the experiments demonstrating that the metabolism of the melanin pigment precursors, tyrosine and dihydroxyphenylalanine, increases the vitamin C requirement of the guinea pig (1) it was learned that those animals receiving tyrosine excreted homogentisic acid in the urine. Furthermore, the amount of the metabolite appeared to be inversely proportional to the amount of ascorbic acid received. Investigation of this point by Sealock and Silberstein (2) has shown that the production of the experimental alkaptonuria is dependent upon a deficiency of the vitamin and that when this deficiency is removed the homogentisic acid no longer appears. On identification of this subst,ance by isolation of the dibenzoylhomogentisamide other tyrosine metabolites were found in the urine of the vitamin C-deficient animals. With the aid of the 2,4-dinitrophenylhydrazine reagent of Penrose and Quastel (3) the corresponding keto acid, p-hydroxyphenylpyruvic acid, was identified. The cY-hydroxy derivative also has been shown to be present but in smaller amount than in the case of the keto acid. Of even greater significance was the finding that’ these metabolites as in the case of the homogentisic acid are no longer excreted when an adequate amount of ascorbic acid is administered to the guinea pigs.