Mitochondrial Function in Diabetes: Pathophysiology and Nutritional Therapeutics
Jeffrey I. Mechanick, Elise M. Brett in Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
α-Lipoic acid (LA; thioctic acid) is an eight-carbon disulfide compound with a single chiral carbon and is easily reduced to a dithiol form, dihydrolipoic acid. The most abundant plant sources of LA are spinach, broccoli, and tomatoes [194]. LA is responsible for (1) protein repair, primarily of oxidized methionine, cysteine and tyrosine residues; (2) free radical scavenging; (3) elevation of glutathione and regeneration of vitamins C and E; and (4) chelation of metals [195]. In humans, LA is synthesized in the liver, where it also functions as a cofactor in multienzyme dehydrogenase complexes, such as PDH, localized in the mitochondria [196]. In a study by Korotchkina et al. [197], various thiol compounds (low-molecular-weight glutathione and cysteine > LA) protect against lipid peroxidation products that mediate mitochondrial free radical damage. In rats, LA partially reverses age-related oxidative stress, mitochondrial dysfunction, and apoptosis [198–200] via (1) increasing reduced glutathione and vitamins C and E; (2) increasing the activity of mitochondrial dehydrogenases and cytochrome-c oxidase; and (3) stimulating mitochondrial Ca++ release and mitochondiral permeability transition pore (mPTP) opening [194,200].
Dietary supplements and food fortification
Geoffrey P. Webb in Nutrition, 2019
α-lipoic acid is a sulphur-containing compound that is synthesised by both animals and plants and so is widely distributed in foods. It is not considered an essential nutrient because of this endogenous synthesis. The α-lipoic acid in food is covalently bound to lysine residues of the enzymes for which it acts as a co-factor. Human gut enzymes do not break the bonds between lipoic acid and lysine and so dietary lipoic acid from food is absorbed as lipolysine. Free lipoic acid is only present in blood if supplements of pure lipoic acid are being taken. The amount in supplements is probably at least 10 times that found in normal diets. Only the R-optical isomer of lipoic acid is normally synthesised in cells whereas chemically synthesised supplements often contain a racemic mixture of R- and S-isomers and the S-isomer would not normally be present in the body. The structure of lipoic acid and its reduced form dihydrolipoic acid are shown in Figure 13.8.
Antioxidant properties and application information
Roger L. McMullen in Antioxidants and the Skin, 2018
Lipoic acid exists in both the oxidized disulfide form (shown above) and the reduced dithiol form (dihydrolipoic acid). Both forms of the molecule have antioxidant activity. It is a cofactor for several enzymes where it carries out a role in oxidative decarboxylation reactions, such as those that occur with alpha-keto acids. It has been cited as a universal antioxidant because it is so versatile in its specificity for radical species and for its ability to function in both lipid and aqueous phases. While lipoic acid is a very strong reducing agent, its endogenous levels in tissues are not very high.
Effect of lipoic acid supplementation on gene expression and activity of glutathione S-transferase enzyme in infertile men
Published in Human Fertility, 2021
Fatemeh Haidari, Javad Mohammadi-Asl, Maria Kavianpour, Mohammadreza Dadfar, Hossein Khadem Haghighian
Lipoic acid (LA) and its reduced form, dihydrolipoic acid (DHLA), have both gained respectable attention due to their roles as biological thiol antioxidants. Several features have been defined for LA, which make it a special antioxidant (Castañeda-Arriaga & Alvarez-Idaboy, 2014). Both LA and DHLA, quench a number of oxygen-free radical species in both lipid and aqueous phase, chelates transition metals, and hampers membrane lipid peroxidation and protein damage via interactions with glutathione (Shila, Kokilavani, Subathra, & Panneerselvam, 2005). It has been postulated that human semen contains a significant amount of glutathione S-transferase (GST) and that the enzyme could attenuate the toxicity of ROS to sperm. The GST gene family produces an isoenzyme that is important in protection against OS (Marí & Cederbaum, 2001), and an increase of ROS associated with reduced activity and gene expression of GST may lead to sperm membrane damage (Chen, Chang, Chen, & Wei, 2002).
Alpha lipoic acid as a novel therapeutic approach to cystinuria
Published in Expert Opinion on Orphan Drugs, 2018
Scott V. Wiener, Thomas Chi, Marshall L Stoller
Alpha lipoic acid (ALA) is an over the counter supplement with anti-oxidant properties that previously has been studied in humans with diabetes mellitus, obesity, Alzheimer’s dementia and a in mouse model of cystinuria [35–39]. Bioavailable lipoic acid comes from endogenous biosynthesis using octanoic acid within the mitochondria and dietary intake through lysine bound lipoyllysine [40,41]. While dietary intake has not been shown to increase free levels of ALA in the blood, 30–40% of orally dosed ALA is absorbed in pharmacokinetic studies [40]. Absorption occurs best on an empty stomach; when compared with fasting, food intake will decrease peak plasma ALA concentrations by approximately 30% and total plasma concentrations by 20%. Metabolism occurs via reduction to dihydrolipoic acid (DHLA).
Long-Term Alpha-Lipoic Acid (ALA) Antioxidant Therapy Reduces Damage in the Cardiovascular System of Streptozotocin-Induced Diabetic Rats
Published in Journal of Dietary Supplements, 2023
Cristiane Simões Coelho Britto Ramos, Vivian Alves Pereira da Silva, Lanna Beatriz Neves Silva Corrêa, Renato de Souza Abboud, Gilson Teles Boaventura, Mauricio Alves Chagas
Alpha-lipoic acid (ALA) is a potent antioxidant. In fact, it is one of the most effective agents in reducing the damage caused by reactive oxygen species (ROS), and is usually found in small amounts in meat and vegetables (24,25). In the tissues, it is readily distributed and rapidly converted into its most active form: dihydrolipoic acid (26). ALA is a nutraceutical whose beneficial effect has been related to its ability to repair cellular oxidative damage in various body tissues (27,28), in addition to its anti-inflammatory effect (29). Owing to its small size and high lipophilicity, it easily crosses biological membranes and inhibits the deleterious effect of reactive oxygen species, thus reducing the oxidation of cellular components (30). It has antioxidant activity in lipo and water-soluble media, either in its oxidized or reduced form (31).
Related Knowledge Centers
- Dihydrolipoamide
- Lipoic Acid
- Organic Compound
- Thiol
- Dithiol
- Optical Rotation
- Lipoamide