Inhibition and activation of the oxidation of homogentisic acid.

The biochemical study of homogentisic acid may be said to have begun with the work of Wolkow and Baumann (3), who demonstrated the relation of this compound to the metabolism of tyrosine. The intervening years have seen much effort expended on studies of the pathway of formation of homogentisic acid, but little on its further metabolism beyond the early discovery that it gives rise to ketone bodies in the animal organism (4) and the more recent finding that fumarylacetoacetic acid is an intermediate in this process (5). Suda and Takeda (6) have reported that the oxidation of homogentisic acid to acetoacetic and fumaric acids in a liver preparation requires the presence of ferrous iron, that phosphate is needed for the complete reaction, and that KCN and various carbonyl-combining reagents do not inhibit the process. The results reported in this paper consist, in part, of a confirmation and extension of the work of Suda and Takeda. In addition, certain major points of disagreement will be noted.