硫辛酰胺脱氢酶对硫辛酸的还原作用。

Reduction of lipoic acid by lipoamide dehydrogenase.

作者信息

Biewenga G P, Dorstijn M A, Verhagen J V, Haenen G R, Bast A

机构信息

Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, Department of Pharmacochemistry, Amsterdam, The Netherlands.

出版信息

Biochem Pharmacol. 1996 Feb 9;51(3):233-8. doi: 10.1016/0006-2952(95)02124-8.

DOI:10.1016/0006-2952(95)02124-8

PMID:8573188

Abstract

Racemic lipoic acid is therapeutically applied in pathologies in which free radicals are involved. The in vivo reduction of lipoic acid may play an essential role in its antioxidant effect. It was found that mitochondrial lipoamide dehydrogenase (LipDH, EC 1.8.1.4.) reduces the R-enantiomer 28 times faster than the S-enantiomer of lipoic acid. Moreover, it was observed that the metabolites of lipoic acid, bisnor-, tetranor-, and beta-lipoic acid are poor substrates of LipDH. S-lipoic acid inhibits the reduction of the R enantiomer only at relatively high concentrations. The reduction of R-lipoic acid by mitochondria-rich tissues may proceed smoothly, even if the racemic mixture is applied. This is of importance in elucidating the molecular mechanism of the pharmacotherapeutic effect of lipoic acid.

摘要

消旋硫辛酸被用于治疗涉及自由基的病症。硫辛酸在体内的还原过程可能在其抗氧化作用中发挥关键作用。研究发现，线粒体脂酰胺脱氢酶（LipDH，EC 1.8.1.4.）还原硫辛酸的R-对映体的速度比S-对映体快28倍。此外，还观察到硫辛酸的代谢产物双去甲硫辛酸、四去甲硫辛酸和β-硫辛酸是LipDH的不良底物。S-硫辛酸仅在相对高浓度时才抑制R对映体的还原。即使应用消旋混合物，富含线粒体的组织对R-硫辛酸的还原过程仍可能顺利进行。这对于阐明硫辛酸药物治疗作用的分子机制具有重要意义。