Biochemistry of Amino Acids - A. Majster 1961

Disorders of amino acid metabolism in certain pathological conditions
Phenylalanine and tyrosine metabolism
Excretion of n-hydroxyphenylpyruvic acid

As mentioned above, n-hydroxyphenylpyruvic acid has been detected in the urine of both humans and animals with ascorbic acid deficiency. It is also frequently present in the urine of patients with Liver disorders [135–137]. Administering Tyrosine to such patients does not increase The excretion of n-hydroxyphenylpyruvic acid; in this case, the metabolic disruption appears to stem from hepatic Cell damage and the associated general decline in enzymatic activity. The excretion of n-hydroxyphenylpyruvic acid has likewise been observed in certain infectious diseases and hematopoietic disorders [137]. In patients with liver damage, the administration of n-hydroxyphenylpyruvic acid intensifies the urine reaction with Millon's reagent; this test has been proposed as a diagnostic tool for evaluating liver function [135–137].

n-Hydroxyphenylpyruvic acid, along with 2,5-dihydroxyphenylpyruvic acid, has been found in the urine of guinea pigs following the feeding of tyrosine and sodium butyrate [134].

The excretion of massive amounts of n-hydroxyphenylpyruvic acid was observed in a patient with a metabolic disorder for which the term "tyrosinosis" was proposed [138]. Administering tyrosine to this patient increased the urinary excretion of n-hydroxyphenylpyruvic acid, alongside tyrosine, n-hydroxyphenyllactic acid, and 3,4-dihydroxyphenylalanine. An elevated output of tyrosine and n-hydroxyphenylpyruvate also occurred after the administration of phenylalanine. Dihydroxyphenylalanine administration increased the excretion of tyrosine and n-hydroxyphenylpyruvate; following the intake of the latter compound, the corresponding α-hydroxy acid appeared in the urine alongside it. Homogentisic acid apparently underwent oxidation, as the ingestion of this compound did not induce alkaptonuria. The exact metabolic block in tyrosinosis has not been definitively established; however, available data point to a defect in the enzyme system responsible for converting tyrosine into homogentisic acid. While tyrosinosis is of little clinical significance (only a single case has been described), its study has played a crucial role in elucidating the normal Metabolic pathways of aromatic Amino Acids.