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

尿石症研究：特别是过氧化物酶体在草酸生成中的作用

• 批准号: 11671548
• 负责人: YANAGAWA Makoto
• 金额: $ 2.24万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671548/
• 关键词: Urolithiasis; Oxalate; Glycolate Oxidase; Glycolate; Glyoxylate

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.

哺乳动物内源性草酸合成的最终步骤是在肝脏中通过乙醛酸将乙醇酸连续氧化为草酸。D，L-2-羟基-3-丁炔酸酯（NaHBA）是乙醇酸氧化酶（GO）的不可逆抑制剂，GO负责乙醇酸氧化为乙醛酸。我们研究了用NaHBA抑制肝GO活性对草酸生成的影响。雄性大鼠经口给予10 mg NaHBA后，测定肝脏中GO活性和24 h尿液中乙醇酸和草酸的浓度。在施用NaHBA后，肝GO活性迅速降低至约20%，保持低水平约10小时，然后在随后的12小时期间逐渐恢复至原始水平的约50%。NaHBA治疗增加尿乙醇酸排泄约4倍，但没有显着减少草酸排泄。尿草酸排泄的增加后，给药的乙醇酸，但不是乙醛酸负荷后，抑制约一半的NaHBA治疗。这些结果表明，部分抑制肝GO活性的NaHBA是不相关的尿草酸排泄的显着变化，可能是因为从或通过乙醇酸的内源性草酸的贡献小于已被认为。

项目成果

Kameda, K., Yanagawa, M., Kawamura, T.: "Effects of D, L-2-Hydroxy-3-Butynoic Acid, an Inhibitor of Glycolate Oxidase, on Oxalogenesis from Glycolate in vivo"Biomedical Research. 21. 139-144 (2000)

龟田 K.、柳川 M.、川村 T.：“乙醇酸氧化酶抑制剂 D,L-2-羟基-3-丁酸对体内乙醇酸生成草酸的影响”生物医学研究。

Kameda K., Yanagawa M., Kawamura J.: "Effects of D, L-2-Hydroxy-3-Butynoic Acid, an Inhibitor of Glycolate Oxidase, on Oxalogenesis from Glycolate in vivo"Biomedical Research. 21. 139-144 (2000)

龟田 K.、柳川 M.、川村 J.：“乙醇酸氧化酶抑制剂 D，L-2-羟基-3-丁酸对体内乙醇酸生成草酸的影响”生物医学研究。

Koji Kameda,MakoTo Yanagawa and Juichi Kawamura: "Effects of D,L-2-Hydroxy-3-Butynoic Acid, and Inhibitor of Glycolate Oxidase, on Oxalogenesis from Glycolate in vivo"Biomedical Research. 21・3. 139-144 (2000)

Koji Kameda、MakoTo Yanakawa 和 Juichi Kawamura：“D,L-2-羟基-3-丁酸和乙醇酸氧化酶抑制剂对体内乙醇酸生成的影响”生物医学研究 21・3。 ）