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The Modification of Cystine — Cleavage of Disulfide Bonds
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
There are several approaches to the cleavage of disulfide bonds in proteins. The majority of studies involve the cleavage of the disulfide bond of cystine to the free thiol group of cysteine by reduction. Reduction has been generally accomplished with a mild reducing agent such as β-mercaptoethanol or cysteine. Gorin and co-workers1 have examined the rate of reaction of lysozyme with various thiols. At pH 10.0 (0.025 M borate), the relative rates of reaction were β-mercaptoethanol (2-mercaptoethanol), 0.2; dithiothreitol, 1.0; 3-mercaptopropionate, 0.4; and 2-aminoethanol, 0.01. The results with aminoethanethiol were somewhat surprising since the reaction (disulfide exchange) involves the thiolate anion and 2-aminoethanethiol would be more extensively ionized than the other mercaptans. Dithiothreitol has been a useful reagent in the reduction of disulfide bonds in proteins2 as introduced by Cleland. Dithiothreitol and the isomeric form, dithioerythritol, are each capable of the quantitative reduction of disulfide bonds in proteins. Furthermore, the oxidized form of dithiothreitol has an absorbance maximum at 283 nm (Δϵ = 273) which can be used to determine the extent of disulfide bond cleavage.2 The UV spectra of dithiothreitol and oxidized dithiothreitol are shown in Figure 1. Insolubilized dihydrolipoic acid has also been proposed for use in the quantitative reduction of disulfide bonds.4
Micronutrients in Cancer Prevention
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Dihydrolipoic acid, a reduced form of alpha-lipoic aid, significantly decreased the tumor incidence and tumor multiplicity in dimethylbenzanthracene (DMBA)/tetrachlorohydroquinone (TCHQ)-induced skin tumor.111 TCHQ is a tumor promoter, and DMBA is a tumor initiator. Dihydrolipoic acid also markedly inhibited expression of inducible nitric oxide synthase (iNOS) enzyme and cyclooxygenase-2 (COX-2) activity, and reduced the tumor incidence and tumor multiplicity of DMBA/TPA (12-O-tetradecanoylphorbol-13-acetate)-induced skin tumor.112 Supplementation with alpha-lipoic acid did not affect the incidence of breast cancer in mice overexpressing HER2/neu, an animal model for breast cancer, or of colon cancer in APCmin mice, a model for intestinal cancer.113 The reasons for these contradictory results between transgenic model of cancer and chemical-induced cancer animal models remain unknown.
Nutritional Ergogenic Aids: Introduction, Definitions and Regulatory Issues
Published in Ira Wolinsky, Judy A. Driskell, Nutritional Ergogenic Aids, 2004
Ira Wolinsky, Judy A. Driskell
a-Lipoic acid and its reduced form, dihydrolipoic acid, are unique and vital antioxidants. They quench a variety of ROS, inhibit reactive oxygen generators and spare other antioxidants. Experimental as well as clinical trials highlight the potential usefulness of a-lipoic acid as a promoter of glucose utilization independent of GLUT-4 and a therapeutic agent to ameliorate adverse effects of diabetes on cataract formation and neuropathy. Although enriching the a-lipoic acid content of diets boosts antioxidant capacities in liver and skeletal muscles of rodents, similar studies have not been performed in humans. Thus, there is no scientific evidence that supplemental a-lipoic acid enhances physical or sport performance in humans, despite promising findings in rodent models. Until convincing data from food fortification or supplementation trials with a-lipoic acid are available, it is merely speculative that this natural antioxidant promotes physical function and performance in humans. The antioxidant properties of a-lipoic acid and its interaction with other key antioxidants such as vitamin E, ascorbate and glutathione will provide numerous opportunities for future research activity in human health promotion and amelioration of disease symptoms.
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).
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).