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在肝脏中乙醛酸氧化乙醇酸为草酸。D，L-2-羟基-3-丁酸(NaHBA)是一种不可逆的乙醇酸氧化酶(GO)抑制剂，参与了乙醇酸氧化成乙醛的反应。我们观察了NaHBA抑制肝脏GO活性对草酸生成的影响。给雄性大鼠灌胃10 mg NaHBA后，测定肝脏GO活性及24 h尿液中乙醇酸和草酸的浓度。给予NaHBA后，肝脏GO活性迅速下降至20%左右，并维持在低水平约10h，然后在随后的12h内逐渐恢复至原来水平的50%左右。NaHBA治疗使尿乙醇酸排泄量增加了约4倍，但并未显著减少草酸排泄量。给予乙醇酸后，尿草酸排泄量的增加，但乙醛负荷后的增加，被NaHBA治疗抑制到大约一半。这些结果表明，NaHBA对肝脏GO活性的部分抑制与尿草酸排泄的显著变化无关，可能是因为来自或通过乙醇酸的内源性草酸合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.