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

哺乳动物内源性草酸合成的最后一步是通过肝脏中的乙醛酸盐将乙醇酸连续氧化为草酸。D， l -2-羟基-3-丁酸酯（NaHBA）是一种不可逆的乙醇酸氧化酶（GO）抑制剂，它负责将乙醇酸氧化成乙醛酸盐。我们检测了NaHBA抑制肝氧化石墨烯活性对草酸生成的影响。雄性大鼠口服10 mg NaHBA后，测定肝脏氧化石墨烯活性和24 h尿液中乙醇酸盐和草酸盐浓度。给药NaHBA后，肝脏氧化石墨烯活性迅速下降至约20%，在10小时内保持低水平，然后在随后的12小时内逐渐恢复至约50%的原始水平。NaHBA治疗使尿中乙醇酸排泄量增加了约4倍，但没有显著减少草酸排泄量。在给药后尿草酸排泄量的增加被NaHBA治疗抑制到大约一半，但在乙醛酸负荷后没有增加。这些结果表明，NaHBA对肝脏氧化石墨烯活性的部分抑制与尿草酸盐排泄的显着变化无关，可能是因为来自或通过草酸盐的内源性草酸生成的贡献比人们认为的要小。

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.