Transamination as a step in tyrosine metabolism.

In recent years the metabolic fate of the individual carbon atoms of the aromatic amino acids has been rather completely elucidated, largely by the use of isotopic labeling techniques (l-3). Very little is known, however, concerning the enzymatic mechanisms whereby the complicated transformation of phenylalanine and tyrosine to acetoacetate is effected. A recent contribution in this direction was the demonstration by Ravdin and Crandall (4) that homogentisic acid is oxidized by liver enzymes to fumarylacetoacetate, which is then hydrolyzed to fumarate and acetoacetate. It has been evident for some time that the first stage of tyrosine oxidation in liver is not an ordinary, oxidative deamination. Thus, the absence of free ammonia in the reaction mixture, the low ratio of oxygen atoms taken up to tyrosine molecules utilized, and the slow rate of deamination by the L-amino acid oxidase all militate against the classical hypothesis. Accordingly, experiments were instituted in this laboratory designed to demonstrate the occurrence of a transamination in the course of tyrosine catabolism in liver preparations. While these experiments were in progress, Cammarata and Cohen (5) published evidence for the ability of tyrosine to transaminate. The data reported herein indicate that this transamination is a prerequisite to any further breakdown of tyrosine on the pathway to acetoacetate. Other investigators have recently presented evidence leading to the same conclusion (6, 7).