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盐合成的最终步骤是乙醇酸盐在肝脏中通过乙醛酸盐连续氧化为草酸盐。 D,L-2-羟基-3-丁酸 (NaHBA) 是乙醇酸氧化酶 (GO) 的不可逆抑制剂，该酶负责将乙醇酸氧化为乙醛酸。我们研究了用 NaHBA 抑制肝脏 GO 活性对草酸生成的影响。雄性大鼠口服10 mg NaHBA后，测定肝脏GO活性以及24小时尿液中乙醇酸和草酸浓度。给予NaHBA后，肝脏GO活性迅速下降至约20%，并保持低水平约10小时，然后在随后的12小时内逐渐恢复至原始水平的约50%。 NaHBA 治疗使尿乙醇酸排泄量增加约 4 倍，但并未显着减少草酸排泄量。 NaHBA 治疗将乙醇酸盐给药后尿草酸盐排泄量的增加（而非乙醛酸盐负荷后的尿草酸盐排泄量增加）抑制到一半左右。这些结果表明，NaHBA 对肝脏 GO 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乙醇酸盐的内源性草酸生成的贡献比人们认为的要小。

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。 ）