Dihydrolipoic acid as an effective cofactor for peptide methionine sulfoxide reductase in enzymatic repair of oxidative damage to both lipid-free and lipid-bound apolipoprotein a-I.

The aim of this study was to examine the possible use of dihydrolipoic acid (DHLA), the reduced form of lipoic acid, in the reduction of oxidized apolipoprotein A-I mediated by peptide methionine sulfoxide reductase (PMSR), and to test the accessibility of methionine sulfoxides in the lipid-bound oxidized apolipoprotein A-I to this reaction. We show that DHLA acts as an effective cofactor for PMSR, mediating restoration of the native secondary structure, tertiary structure, stability, and lipid-binding properties of the native unoxidized protein. Reconstituted high-density lipoproteins were used to demonstrate effective enzymatic reduction of the lipid-bound oxidized protein in the presence of DHLA. These findings suggest that the enzymatic repair of oxidative damage to intact lipoproteins could provide a model of a possible repair mechanism active in vivo during oxidative stress and that the restoration of high-density lipoprotein function could be one of the therapeutic benefits of lipoic acid.