DESCRIPTION Alpha-lipoic acid, also known as thioctic acid, is a disulfide compound that is a cofactor in vital energy-producing reactions in the body. It is also a potent biological antioxidant. Alpha-lipoic acid was once thought to be a vitamin for animals and humans. It is made endogenously in humans—the details of its synthesis are still not fully understood—and so it is not an essential nutrient. There are, however, certain situations, for example, diabetic polyneuropathy, where alpha-lipoic acid might have conditional essentiality. And recent research indicates that the antioxidant roles of alpha-lipoic acid may confer several health benefits. Alpha-lipoic acid is found widely in plant and animal sources.
Most of the metabolic reactions in which alpha-lipoic acid participates occur in mitochondria. These include the oxidation of pyruvic acid (as pyruvate) by the pyruvate dehydrogenase enzyme complex and the oxidation of alpha-ketoglutarate by the alpha-ketoglutarate dehydrogenase enzyme complex. It is also a cofactor for the oxidation of branched-chain amino acids (leucine, isoleucine and valine) via the branched-chain alpha-keto acid dehydrogenase enzyme complex.
Alpha-lipoic acid is approved in Germany as a drug for the treatment of ... read more, make a purchase and get Members Area access and ... read more, make a purchase and get Members Area access. Alpha-lipoic acid contains a chiral center and consists of two entantiomers, the natural R- or D- entantiomer and the S- or L- entantiomer. Commercial preparations of alpha-lipoic acid consist of the racemic mixture, i.e. a 50/50 mixture of the R- and E-entantiomers. It is represented by the following chemical structure:
Alpha-Lipoic acid
Alpha-lipoic acid has a variety of names. In addition to being known as alpha-lipoic acid and thioctic acid, it is also known as lipoic acid, 1,2-dithiolane-3-pentanoic acid; 1,2-ditholane-3-valeric acid; 6,8-thiotic acid; 5-[3-C1,2-dithiolanyl)]-pentanoic acid; delta-[3-(1,2-dithiacyclopentyl)] pentanoic acid; acetate replacing factor and pyruvate oxidation factor. Alpha-lipoic acid is water-insoluble. Although the details of its synthesis have yet to be worked out, alpha-lipoic acid is synthesized in mitochondria; octanoic acid and L-cysteine (for its sulfur) are precursors in its synthesis.
ACTIONS AND PHARMACOLOGY
ACTIONS Alpha-lipoic acid has biological antioxidant activity, antioxidant recycling activity and activity in enhancing biological energy production.
MECHANISM OF ACTION Alpha-lipoic acid and its reduced metabolite, dihydrolipoic acid (DHLA), form a redox couple and may scavenge a wide range of reactive oxygen species. Both alpha-lipoic acid and DHLA can scavenge hydroxyl radicals, the nitric oxide radical, peroxynitrite, hydrogen peroxide and hypochlorite. Alpha-lipoic acid, but not DHLA, may scavenge singlet oxygen, and DHLA, but not alpha-lipoic acid, may scavenge superoxide and peroxyl reactive oxygen species. Alpha-lipoic acid has been found to decrease urinary isoprostanes, O-LDL and plasma protein carbonyls, markers of oxidative stress. Further, alpha-lipoic acid and its redox couple DHLA have been found to have antioxidant activity in aqueous, as well as in lipophilic regions, and in extracellular and intracellular environments. Finally, with regard to alpha-lipoic acid's antioxidant activity, alpha-lipoic acid appears to participate in the recycling of other important biologic antioxidants, such as vitamins E and C, ubiquinone and glutathione. Exogenous alpha-lipoic acid has been shown to increase ATP production and aortic blood flow during reoxygenation after hypoxia in a working heart model. It is thought that this is due to its role in the oxidation of pyruvate and alpha-ketoglutarate in the mitochondria, ultimately enhancing energy production. This activity, and possibly its antioxidant activity, may account for its possible benefit in ... read more, make a purchase and get Members Area access
PHARMACOKINETICS Most pharmacokinetic studies have been performed in animals. Alpha-lipoic acid is absorbed from the small intestine and distributed to the liver via the portal circulation and to various tissues in the body via the systemic circulation. The natural R-entantiomer is more readily absorbed than the L-entantiomer and is the more active form. Alpha-lipoic acid readily crosses the blood-brain barrier. It is found, after its distribution to the various body tissues, intracellularly, intramitochondrialy and extracellularly. Alpha-lipoic acid is metabolized to its reduced form, dihydrolipoic acid (DHLA), by mitochondrial lipoamide dehydrogenase. DHLA, together with lipoic acid, form a redox couple. It is also metabolized to lipoamide, which functions as the lipoic acid cofactor in the multienzyme complexes that catalyze the oxidative decarboxylations of pyruvate and alpha-ketoglutarate. Alpha-lipoic acid may be metabolized to dithiol octanoic acid, which can undergo catabolism.
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Coenzyme Q10 (CoQ10)
DESCRIPTION Coenzyme Q10 or CoQ10 belongs to a family of substances called ubiquinones. Ubiquinones, also known as coenzymes Q and mitoquinones, are lipophilic, water-insoluble substances involved in electron transport and energy production in mitochondria. The basic structure of ubiquinones consists of a benzoquinone "head" and a terpinoid "tail." The "head" structure participates in the redox activity of the electron transport chain. The major difference among the various coenzymes Q is in the number of isoprenoid units (5-carbon structures) in the "tail." Coenzymes Q contain one to 12 isoprenoid units in the "tail"; 10 isoprenoid units are common in animals.
Coenzymes Q occur in the majority of aerobic organisms, from bacteria to plants and animals. Two numbering systems exist for designation of the number of isoprenoid units in the terpinoid "tail": coenzyme Qn and coenzyme Q(x). N refers to the number of isoprenoid side chains, and x refers to the number of carbons in the terpinoid "tail" and can be any multiple of five. Thus, coenzyme Q10 refers to a coenzyme Q having 10 isoprenoid units in the "tail." Since each isoprenoid unit has five carbons, coenzyme Q10 can also be designated coenzyme Q(50). The structures of coenzymes Q are analogous to those of vitamin K2. Coenzyme Q10 is also known as Coenzyme Q(5O), CoQ10, CoQ(50), ubiquinone (50), ubiquinol— 10 and ubidecarerone. Chemically, CoQ10 is known as 2, 3-dimethyoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, and its structural formula is:
CoEnzyme Q10 It is a solid wax-like substance. CoQ10 is the predominant form in humans, and CoQ9 is the predominant form in rats. Supplemental CoQ10 is typically derived from tobacco leaf extracts and fermented sugar cane and beets.
MECHANISM OF ACTION Since the actions of supplemental CoQ10 have yet to be clarified, the mechanism of these actions is a matter of speculation. However, much is known about the biochemistry of CoQ10. CoQ10 is an essential cofactor in the mitochondrial electron transport chain, where it accepts electrons from complex I and II, an activity that is vital for the production of ATP.
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