On Excretion of Homogentisic Acid

The literature on alcaptonuria has been well summarized (1--6). Paschkis et al. (7) reported that thiouracil and para-aminobenzoic acid inhibited the in vitro conversion of tyrosine to melanin by tryrosinase, and White (8) found that thiouracil inhibited melanuria. Lerner and associates (9) noted that the tyrosinase of mouse melanoma is a copper protein whose activity can be inhibited by the addition of substances which combine with copper (phenylthiourea and others) and then restored by the addition of an excess of copper. Since homogentisic acid is an oxidative product of tyrosine, it seemed worthwhile to determine whether the production of homogentisic acid could be inhibited by thiouracil and para-aminobenzoic acid. When 3, 5, diiodotyrosine is fed to rabbits, about 60%o (Foster and Gutman [10] ) is excreted as 3, 5, di-iodo4-hydroxyphenyllactic acid. It, therefore, occurred to us that, since the number 5 carbon on the benzene ring is blocked by iodine, the alcaptonuric patient would not be able to utilize di-iodotyrosine as he would 1-tyrosine to form homogentisic acid (2, 5, dihydroxyphenylacetic acid).Soderbergh (12) observed that the daily administration of 3.0 gm. of potassium iodide to an alcaptonuric decreased the urinary excretion of homogentisic acid by 2.0 gm. per day. This compound was administered to our patient in an attempt to influence similarly the excretion of homogentisic acid.