Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers.
The reduction of exogenous alpha-lipoic acid to dihydrolipoate by mammalian cells and tissues confers additional antioxidant protection to the cell. Both (R+) and (S-) isomers of alpha-lipoic acid were analyzed as substrates with glutathione reductase from several sources and with mammalian lipoamide dehydrogenase. Mammalian glutathione reductase catalyzed faster reduction of (S)-lipoic acid (1.4-2.4-fold greater activity) than of (R)-lipoic acid, whereas lipoamide dehydrogenase had a very marked preference for (R)-lipoic acid (18-fold greater activity) over (S)-lipoic acid. Mammalian glutathione reductase showed better affinity for (S)-lipoic acid substrate; Km values were 3.5 mM for (S)-lipoic acid and and 7 mM for (R)-lipoic acid. Glutathione reductase from yeast reduced lipoic acid less efficiently than the mammalian enymes, had a Km for both stereoisomers of about 10 mM, and showed little stereospecificity. Although (S)-lipoic acid is not formed in nature, these findings indicate that exogenous (S)-lipoic acid may have a useful role as an antioxidant for mammalian systems.
Pick
U
U
Department of Biochemistry, Weizman Institute, Rehovot, Israel.
Haramaki
N
N
Constantinescu
A
A
Handelman
G J
GJ
Tritschler
H J
HJ
Packer
L
L
D000818:Animals; D002417:Cattle; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D013379:Substrate Specificity; D008063:Thioctic Acid / Q000737:chemistry / Q000378:metabolism
D008063:Thioctic Acid; D008058:Dihydrolipoamide Dehydrogenase; D005980:Glutathione Reductase