Lipoic Acid - Biological Sources and Degradation

Biological Sources and Degradation

Lipoic acid is found in almost all foods, but slightly more so in kidney, heart, liver, spinach, broccoli, and yeast extract. Naturally occurring lipoic acid is always covalently bound and not readily available from dietary sources. Additionally, the amount of lipoic acid present is very low. For instance, the purification of lipoic acid to determine its structure used an estimated 10 tons of liver residue, which yielded 30 mg of lipoic acid. As a result, all lipoic acid available as a supplement is chemically synthesized.

Baseline levels (prior to supplementation) of RLA and R-DHLA have not been detected in human plasma. RLA has been detected at 12.3−43.1 ng/mL following acid hydrolysis, which releases protein-bound lipoic acid. Enzymatic hydrolysis of protein bound lipoic acid released 1.4−11.6 ng/mL and <1-38.2 ng/mL using subtilisin and alcalase, respectively. It has not been determined whether pre-supplementation levels of RLA derive from food sources, mitochondrial turnover and salvaging or from gut microbes but low levels have been correlated to a variety of disease states.

Digestive proteolytic enzymes cleave the R-lipoyllysine residue from the mitochondrial enzyme complexes derived from food but are unable to cleave the (R)-lipoic acid--lysine amide bond. Both synthetic lipoamide and (R)-lipoyl--lysine are rapidly cleaved by serum lipoamidases which release free (R)-lipoic acid and either -lysine or ammonia into the bloodstream. It has recently been questioned whether or not food sources of RLA provide any measurable benefit nutritionally or therapeutically due to the very low concentrations present. Lipoate is the conjugate base of lipoic acid and as such is the most prevalent form under physiologic conditions. Most endogenous RLA is not "free" because octanaote is attached to the enzyme complexes that use it via LipA. The sulfur atoms derive from the amino acid L-cysteine and add asymmetrically to octanoate by lipoate synthase, thus generating the chiral center at C6. Endogenous RLA has been found outside the mitochondria associated with the nucleus, peroxisomes and other organelles. It has been suggested that the reduced form, R-DHLA may be the substrate for membrane-associated prostaglandin E-2 synthase (mPGES2).