Inhibition of oxalate synthesis: In vitro studies using analogues of oxalate and glycolate

Abstract

Fourteen analogues of oxalate or glycolate were studied as potential inhibitors of oxalate synthesis. Their inhibitory properties were determined in human erythrocytic preparations, in which the enzymatic activity seems to be predominantly, if not exclusively, lactic dehydrogenase (LDH), and in a partially purified glycolic acid oxidase preparation from rat liver. Evidence is presented that, in rat liver, nicotinamide-adenine dinucleotide (NAD)-dependent oxidation, probably catalyzed by LDH, is the major pathway for oxalate synthesis rather than flavin mononucleotide (FMN)-dependent oxidation catalyzed by glycolic acid oxidation. Of the oxalate analogues, oxalatehydrazide was found to be the most potent inhibitor of LDH-catalyzed oxalate synthesis. None of the oxalate analogues were very active as an inhibitor of glycolic acid oxidase. Hydroxymethanesulfonate was demonstrated to be a potent inhibitor of erythrocytic LDH, and the most effective compound studied for glycolic acid oxidase inhibition. Five of its structural analogues-acetoxymethanesulfonate, aminomethanesulfonate, iodomethanesulfonate, chloromethanesulfonate, and fluoromethanesulfonate-were less active in the two in vitro systems used. Other approaches to the control of oxalate synthesis are discussed. These studies furnish a background for the testing of inhibitors of oxalate synthesis in vivo. © 1972.