R-Alpha lipoic acid (a-LA) is synthesized in the mitochondria of plants and animals, including humans. Natural a-LA is covalently bound to proteins via lysine; thus only minimal free a-LA enters the circulation after biosynthesis or eating a-LA-rich food (22). The lipoamide is a required co-factor for two enzymes in the citric acid cycle. It is also essential for the formation of a cofactor required in nucleic acid synthesis and for the metabolism of branched-chain amino acids.
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Figure 12 Representative photograph of inhibition of photocarcinogenesis in mice treated with genistein. (A) Hairless mice irradiated with 0.3 kJ/m2 thrice weekly for 25 weeks. (B) Mice treated with 1 pmol genistein before UVB exposure. (C) Mice treated with 5 pmol genistein before UVB irradiation. Source: From Ref. 135. |
With oral supplements of free a-LA, unbound a-LA is transported to tissues (22). Free a-LA is rapidly metabolized by the liver, so that the half-life in blood after absorption is only about 30 minutes, limiting the amount delivered (22). High tissue levels are short-lived since most free a-LA is rapidly reduced to dihydrolipoic acid (DHLA), as shown in Figure 13 (21,22).
Notwithstanding this transient availability, free a-LA has been shown to be therapeutic for autoimmune liver disease by binding autoantibodies, heavy metal intoxication by trapping circulating metals, diabetic polyneuropathy by preventing oxidative damage, and mushroom poisoning (22). Although not normally found in significant amounts in the skin, a-LA is a good candidate for topical application (21,154):
• As a small, stable molecule, it could successfully be percutaneously absorbed.
• As a potent antioxidant it might protect from UV and other free radical environmental changes;
• Because it is soluble in both aqueous and lipid environments, it can interact with oxidants and antioxidants in many cellular compartments.
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Figure 13 The molecular structures of a-lipoic acid and dihydrolipoic acid. |
