Reduction of lipoic acid by lipoamide dehydrogenase

被引:41
作者
Biewenga, GP
Dorstijn, MA
Verhagen, JV
Haenen, GRMM
Bast, A
机构
[1] Leiden/Amsterdam Ctr. for Drug Res., Vrije Universiteit, Division of Molecular Pharmacology, 1081 HV Amsterdam
关键词
lipoic acid; dihydrolipoic acid; thioctic acid; lipoamide dehydrogenase; antioxidant; enzymatic reduction;
D O I
10.1016/0006-2952(95)02124-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:233 / 238
页数:6
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