The nature of the defect in tyrosine metabolism in alcaptonuria.

Alcaptonuria is a rare, hereditary, metabolic disorder characterized by a defect in the oxidation of tyrosine (l-3). In this condition homogentisic acid, an intermediary product of tyrosine degradation in mammalian liver, is excreted in the urine. This disorder has been attributed to an abnormality of the enzyme system, homogentisic acid oxidase, but the exact nature of the abnormality has not been determined. The recent opportunity to perform a liver biopsy during abdominal surgery on a patient with alcaptonuria made it possible to determine more precisely the nature of the defect in homogentisic acid oxidase. In addition, the activities of the other enzymes known to participate in tyrosine catabolism were assayed and compared with those of non-alcaptonuric liver preparations. It was possible to establish with reasonable certainty that the defect in alcaptonuria is limited to the enzyme, homogentisic acid oxidase, that there is a failure to synthesize active enzyme, and that the metabolic block is essentially complete.