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Alpha-Lipoic Acid Supplementation Protects Enzymes From Damage By Nitrosative And Oxidative Stress, Sylvia Hiller, Robert Dekroon, Eric D. Hamlett, Longquan Xu, Cristina Osorio, Jennifer Robinette, Witold Winnik, Stephen Simington, Nobuyo Maeda, Oscar Alzate, Xianwen Yi

United States Environmental Protection Agency: Staff Publications

Background: S-nitrosylation of mitochondrial enzymes involved in energy transfer under nitrosative stress may result in ATP deficiency. We investigated whether α-lipoic acid, a powerful antioxidant, could alleviate nitrosative stress by regulating S-nitrosylation,which could result in retaining themitochondrial enzyme activity.

Methods: In this study, we have identified the S-nitrosylated forms of subunit 1 of dihydrolipoyllysine succinyltransferase (complex III), and subunit 2 of the α-ketoglutarate dehydrogenase complex by implementing a fluorescence-based differential quantitative proteomics method.

Results: We found that the activities of these two mitochondrial enzymes were partially but reversibly inhibited by S-nitrosylation in cultured endothelial cells, and that their activities …