Reduction of lipoic acid by lipoamide dehydrogenase
Reduction of lipoic acid by lipoamide dehydrogenase
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DOI：
10.1016/0006-2952(95)02124-8
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发表时间：
1996-02-09
影响因子：
5.8
通讯作者：
Bast, A
中科院分区：
文献类型：
--
作者：
Biewenga, GP;Dorstijn, MA;Bast, A
外消旋硫辛酸在治疗上应用于涉及自由基的病理。在体内减少硫辛酸可能发挥其抗氧化作用的重要作用。发现线粒体硫辛酰胺脱氢酶（LipDH，EC 1.8.1.4.）比硫辛酸的S-对映体快28倍地还原R-对映体。此外，观察到硫辛酸的代谢物双去甲-、四去甲-和β-硫辛酸是LipDH的不良底物。S-硫辛酸仅在相对高的浓度下抑制R对映体的还原。即使使用外消旋混合物，富含维生素A的组织对R-硫辛酸的还原也可以顺利进行。这对阐明硫辛酸药理作用的分子机制具有重要意义。
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.