THE IN VITRO METABOLISM OF 2-HYDROXYNICOTINIC ACID IN HUMAN ERYTHROCYTES AND PLATELETS

¹ Department of Biochemistry and Drug Metabolism and Department of Biochemical Nutrition, Hoffmann-La Roche Inc.

The metabolism of 2-hydroxynicotinic acid (2-HNA) was investigated in intact human erythrocytes and platelets and in a phosphate buffer extract of erythrocyte acetone powder. The only metabolite detected on incubation of 2-HNA with the erythrocyte acetone powder preparation was the N-ribotide, 2-HNA-ribose-P. Incubation of 2-HNA with intact erythrocytes or platelets resulted in the formation of the N-riboside, 2-HNA-ribose, which was also formed on incubation of 2-HNA-ribose-P with lysed platelets. Nicotinic acid inhibited 2-HNA metabolism in both the intact cells and in the acetone powder preparation. It is concluded that nicotinic acid mononucleotide phosphoribosyltransferase mediates the conversion of 2-HNA to 2-HNA-ribose-P, and that this intermediate is dephosphorylated to 2-HNA-ribose. This reaction sequence would account for the extensive urinary excretion of 2-HNA-ribose in humans and animals administered 2-HNA.