Research for Urolithiasis : especially, the Role of Peroxisomal Enzyme in Oxalogenesis

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A terminal step of endogenous oxalate synthesis in mammals is the successive oxidation of glycolate to oxalate via glyoxylate in the liver. D,L-2-hydroxy-3-butynoate (NaHBA) is an irreversible inhibitor of glycolate oxidase (GO), which is responsible for the oxidation of glycolate to glyoxylate. We examined the effect on oxalogenesis of inhibiting hepatic GO activity with NaHBA. The GO activity in the liver and the concentrations of glycolate and oxalate in the 24-h urine were determined after 10 mg of NaHBA was given orally to male rats. After administration of NaHBA, hepatic GO activity decreased rapidly to about 20 %, remained low for about 10 h, and then gradually recovered during the subsequent 12-hour period to about 50 % of the original level. The NaHBA treatment increased urinary glycolate excretion by about 4-fold, but did not significantly reduce oxalate excretion. The increase in urinary oxalate excretion after administration of glycolate, but not that after glyoxylate loading, was suppressed to about half by the NaHBA treatment. These results indicate that the partial inhibition of hepatic GO activity by NaHBA was not associated with a marked change in urinary oxalate excretion, probably because the contribution of endogenous oxalogenesis from or via glycolate was smaller than has been believed.