Redox regulation of cell functions by α-lipoate: biochemical and molecular aspects

α-lipoate also known as thioctic acid, 1,2-dithiolane-3-pentanoic acid, 1,2-dithiolane-3-valeric acid or 6,8-thioctic acid has generated considerable clinical interest as a thiol-replenishing and redoxmodulating agent [16–18,27]. Lipoate has been used for a long time in Germany to treat complications associated with diabetes [11]. Recently, lipoate has also been introduced to the United States as a metabolic antioxidant. As early as in the 1950s lipoate has been identified as an essential cofactor in oxidative metabolism. Biologically, lipoate exists as lipoamide in at least five proteins where it is covalently linked to a lysyl residue. Three of the lipoamide-containing proteins are present in the E2 enzyme dihydrolipoyl acyltransferase, which is different in each of the complexes and specific for the substrate of the complex. One lipoyl residue is found in protein X, which is the same in each complex. The fifth lipoamide residue is present in the glycine cleavage system [5]. Recently, lipoic acid has been detected in the form of lipoyllysine in various natural sources. In the plant material studied, lipoyllysine content was highest in spinach (3.15 mg/g dry weight; 92.51 mg/mg protein). Lipoyllysine was also detected in animal tissues. The concentration of lipoyllysine in bovine kidney and heart were 2.64± 1.23 and 1.51± 0.75 mg/g dry weight, respectively [13]. To develop an understanding of the therapeutic potential of lipoate supplementation, much of the current interest is focused on the fate of exogenously supplemented non-protein bound lipoate in cell culture, animal and human clinical studies. Lipoate, in its native form, contains a disulfide bond. Reduction of this disulfide results in the conversion of lipoate to the corresponding vicinal dithiol, dihydrolipoate (DHLA).