Influence of some therapeutic agents on the biosynthesis of uric acid

Abstract

Liver xantindehydrogenase of various sources -chicken, rat and pig appears to be inhibited by an excess of substrate [Xantine] 10-4 M. A similar phenomenon has been observed with the dehydrogenase present in horse leucocytes.

The following drugs behave in vitro as competitivo inhibitors of chicken xan­tindehydrogenase, and the corresponding inhibition constants (Ki) have been established: salicylic, acetylsalicylic, p-hy-droxybenzoic and p-aminobenzoic acids, phenylbutazone, colchicine and antipyrine.

When an isolated chicken liver is perfused with any of the mentioned drugs, the uricogenic rate of the gland is correspondingly reduced.

Intraperitoneal adininistration of col­ chicine to rats and chickens, appears to greatly diminish liver xantindehydrogenase activity. Similar experiments performed by injecting salicylic and ace­ tylsalicylic acids, or phenylbutazone, seem to reduce only slightly the activity of the enzyme.

The powerful effeets induced in vivo by the injection of colchicine to animáis, and the excellent therapeutical results obtained when small doses of the alkaloid are given to gouty patients, cannot be simply explained by its inhibitory action upon xantindehydrogenase. Some experiments we have in course indicate that colchicine also interferes with other enzymatic systems wliich seem to work coupled with xantindehydrogenase in the hepatic cell.