What is Glutathione (GSH)?
Biochemistry and Metabolism:
Reduced Glutathione (GSH) is a linear tripeptide of L-glutamine, L-cysteine, and glycine. Technically N-L-gamma-glutamyl-cysteinyl glycine or L-Glutathione, the molecule has a sulfhydryl (SH) group on the cysteinyl portion, which accounts for its strong electron-donating character.
As electrons are lost, the molecule becomes oxidized, and two such molecules become linked (dimerized) by a disulfide bridge to form Glutathione disulfide or oxidized Glutathione (GSSG). This linkage is reversible upon re-reduction.
Glutathione is under tight homeostatic control both intracellularly and extracellularly. A dynamic balance is maintained between GSH synthesis, it’s recycling from GSSG/oxidized Glutathione, and its utilization.
Glutathione synthesis involves two closely linked, enzymatically-controlled reactions that utilize ATP. First, cysteine and glutamate are combined by gamma-glutamyl cysteinyl synthetase. Second, GSH synthetase combines gamma-glutamylcysteine with glycine to generate Glutathione. As Glutathione levels rise, they self-limit further GSH synthesis; otherwise, cysteine availability is usually rate-limiting. Fasting, protein-energy malnutrition, or other dietary amino acid deficiencies limit Glutathione synthesis.
Glutathione recycling is catalyzed by Glutathione disulfide reductase, which uses reducing equivalents from NADPH to reconvert GSSG to 2GSH. The reducing power of ascorbate helps conserve systemic Glutathione.
Glutathione is used as a cofactor by (1) multiple peroxidase enzymes, to detoxify peroxides generated from oxygen radical attack on biological molecules; (2) transhydrogenases, to reduce oxidized centers on DNA, proteins, and other biomolecules; and (3) Glutathione S-transferases (GST) to conjugate Gluathione with endogenous substances (e.g., estrogens), exogenous electrophiles (e.g., arene oxides, unsaturated carbonyls, organic halides), and diverse xenobiotics. Low GST activity may increase risk for disease—but paradoxically, some Glutathione conjugates can also be toxic.
Direct attack by free radicals and other oxidative agents can also deplete Glutathione. The homeostatic Glutathione redox cycle attempts to keep Glutathione repleted as it is being consumed. Amounts available from foods are limited (less that 150 mg/day), and oxidative depletion can outpace synthesis.
The liver is the largest Glutathione reservoir. The parenchymal cells synthesize GSH for P450 conjugation and numerous other metabolic requirements—then export GSH as a systemic source of SH-reducing power. Glutathione is carried in the bile to the intestinal luminal compartment. Epithelial tissues of the kidney tubules, intestinal lining and lung have substantial P450 activity—and modest capacity to export Glutathione.
Glutathione equivalents circulate in the blood predominantly as cystine, the oxidized and more stable form of cysteine. Cells import cystine from the blood, reconvert it to cysteine (likely using ascorbate as cofactor), and from it synthesize GSH. Conversely, inside the cell, Glutathione helps re-reduce oxidized forms of other antioxidants—such as ascorbate and alpha-tocopherol.
Mechanism of Action:
Glutathione is an extremely important cell protectant. It directly quenches reactive hydroxyl free radicals, other oxygen-centered free radicals, and radical centers on DNA and other biomolecules. Glutathione is a primary protectant of skin, lens, cornea, and retina against radiation damage and other biochemical foundations of P450 detoxification in the liver, kidneys, lungs, intestinal, epithelia and other organs.
Glutathione is the essential cofactor for many enzymes that require thiol-reducing equivalents, and helps keep redox-sensitive active sites on enzyme in the necessary reduced state. Higher-order thiol cell systems, the metallothioneins, thioredoxins and other redox regulator proteins are ultimately regulated by Glutathione levels—and the GSH/GSSG redox ratio. GSH/GSSG balance is crucial to homeostasis—stabilizing the cellular biomolecular spectrum, and facilitating cellular performance and survival.
Glutathione and its metabolites also interface with energetics and neurotransmitter syntheses through several prominent metabolic pathways. Glutathione availability down-regulates the pro-inflammatory potential of leukotrienes and other eicosanoids. Recently discovered S-nitroso metabolites, generated in vivo from Glutathione and NO (nitric oxide), further diversify Glutathione's impact on metabolism.
Monograph provided by Alternative Medicine Review (www.thorne.com)
Glutathione Used in Various Disease States:
Essential GSH™ is a breakthrough liquid formulation uniquely designed to increase the systemic bioavailability of Glutathione, via a liposomal-based delivery. It provides Glutathione in a convenient, absorbable form that your body can rapidly use using pharmaceutical grade liposomes. Because liposomes are made from the same material that your cell membranes are made from, it fuses with cell membranes and allows for absorption of Glutathione into the cells. > learn more or click to purchase Essential GSH
Wellness Glutathione is Different:
Wellness Pharmacy® is proud to announce the approval of its patent (#6,835,811) on the method of preparation and storage of injectable reduced l-Glutathione. Injectable reduced l-Glutathione must be properly prepared and stored or it may oxidize in a matter of hours rendering it ineffective.
The first of its kind, Wellness’ patented method ensures and enhances it’s stability allowing physicians to administer the product in near 100% reduced form - always. It can be prepared in unit-of-dose vials or multi-dosed vials; whichever is more convenient for your office. This patent also covers inhaled Glutathione.
The patent can be viewed at www.uspto.gov. Wellness’ Glutathione is referenced on pages 108 and 195 in The Detoxx Book™, page 293 of The Better Brain Book, and pages 29, 78, and 96 of BrainRecovery.com. Wellness Pharmacy has made it a point to be on the progressive side of medicine, knowing that customer satisfaction is—and will continue to be—the building block of our success. We look forward to serving you in the future.