This will be the first of many articles on glutathione, especially the reduced glutathione form known as GSH – the ideal glutathione or GSH product is reduced (GSH), stable, absorbable, efficacious, and probably have a patent (it will be a race to get it right).
Glutathione is the master Antioxidant.
Our bodies depend on GSH for the removal of toxins and GSH is at the heart of all immune functions. Glutathione is a tripeptide (L-glutamic acid, L-cysteine, and Glycine) that is known as the most prominent nonenzymatic antioxidant in the human body, and is a substrate of a regulatory system of enzymes involved in regulating glutathione metabolism, and while this particular tripeptide is somewhat resistant to hydrolysis, it is still mostly digested in the intestines. In effect, glutathione is an indirect and expensive way to provide dietary L-cysteine. Which is ultimately all that is needed for the benefits of glutathione.
Beyond being an endogenous antioxidant, glutathione is present in the human diet in food products, although the doses consumed in even the most prolific diets is significantly smaller than oral doses of glutathione or its precursor (N-Acetylcysteine) and dietary glutathione does not correlate with overall glutathione activity. Glutathione is not stable in the blood, and whether via oral or intravenous administration, glutathione will be readily degraded into L-cysteine or other sulfur containing molecules. Glutathione is synthesized intracellularly, and while it can be effluxed from a cell it tends to be hydrolyzed to its constituent amino acids to then be taken back up by cells and resynthesized intracellularly into Glutathione.
Glutathione is a tripeptide molecule found in mammalian bodies. According to Mark Hyman, MD, “glutathione is one of the hottest topics in both natural health and medical circles today.” The reasons for this are not completely understood, but we do know that glutathione is extremely important for maintaining intracellular health. Glutathione is a highly important antioxidant in the human body with no significant promise for a dietary supplement due to rapid digestion. Its metabolite, L-cysteine, can increase glutathione in the body but consuming L-cysteine via glutathione is inefficient and costly. Supplementation of glutathione is thought to support this pool of glutathione in a cell and thus maintain the efficacy of the entire glutathione system.
Reduced Glutathione is at the heart of all immune functions
Low GSH levels are seen in many diseases such as AIDS, advanced diabetes, and cancers. GSH is commonly the most abundant low molecular mass thiol in animal and plant cells. GSH is formed from glutamate, cysteine, and glycine, but it possesses an unusual peptide bond. As a result, GSH is relatively stable in the cell and is cleaved by GGT only at external sides on the membranes of certain cells.
The steady-state level of cellular GSH is provided by the balance between production and consumption, as well as by extrusion from the cell as reduced, oxidized, or bound forms. In addition to detoxification of reactive species and electrophiles such as methylglyoxal, GSH is involved in protein glutathionylation and several other processes, such as the biosynthesis of leukotrienes and prostaglandins, and reduction of ribonucleotides. GSH is extensively used as a co-substrate by glutathione peroxidases (GPx). Although GSH is synthesized in the cytosol, it is distributed to different intracellular organelles where it is used in organelle-specific functions related to its role in the regulation of cellular redox status. The largest amount of cellular GSH is located in mitochondria.
As mentioned above, GSH is synthesized only in the cytosol and is transported into intracellular organelles. GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. In the case of N-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (acetaminophen), which becomes toxic when GSH is depleted by an overdose of acetaminophen, glutathione is an essential antidote to overdose. GSH is a key cellular antioxidant and plays a major role in the phase 2 metabolic clearance of electrophilic xenobiotics. GSH is an extremely important cell protectant.
Probably most importantly, GSH is responsible for protection against ROS and RNS, and detoxification of endogenous and exogenous toxins of an electrophilic nature. In this respect, GSH is often considered to be a key player of the defense system. Reduced glutathione is assembled from three peptides and is synthesized from cysteine or methionine from food sources. Reduction is a process where oxygen is lost and hydrogen and electrons are gained, so reduced glutathione is missing an oxygen molecule but has an extra donor electron! Reduced glutathione is in the correct form that you would want because it is the “activated form”. Thus their basal ratio of oxidized to reduced glutathione is significantly higher than that of patients who express glucose-6-phosphate dehydrogenase, normally, making them unable to effectively respond to high levels of reactive oxygen species, which cause cell lysis. Reduced glutathione is a novel regulator of vernalization-induced bolting in the rosette plant Eustoma grandiflorum. Reduced glutathione is required for pertussis toxin secretion by Bordetella pertussis.
The cell-specific anti-proliferative effect of reduced glutathione is mediated by gamma-glutamyl transpeptidase-dependent extracellular pro-oxidant reactions. Under conditions of oxidative stress, the liver exports oxidized glutathione into bile in a concentrative fashion, whereas under basal conditions, mainly reduced glutathione is exported into bile and blood. Reduced glutathione is essential for maintaining the normal structure of red blood cells and for keeping hemoglobin in the ferrous state. In healthy human skeletal muscle fibres, the level of reduced glutathione is higher in aerobic type I fibres than in anaerobic type II fibres. Reduced glutathione is not required for measurement of alpha-D-glucosidase in human seminal plasma. Reduced glutathione is nitrosated in aerobic solutions of nitric oxide under physiological conditions; however, the extent of S-nitrosation was found to be dependent on the inorganic anions present. Reduced glutathione is involved in the synthesis and repair of DNA, and enhances the antioxidant activity of vitamin C, the transport of amino acids, and the detoxification of harmful compounds. Reduced glutathione is important for cell health and liver function. Reduced glutathione is an efficient chelator of cuprous copper.
The biosynthesis pathway for glutathione is found in some bacteria, such as cyanobacteria and proteobacteria, but is missing in many other bacteria. Glutathione is not an essential nutrient for most humans (except those with autism or on the ASD spectrum or people with MTHFR), since it can be biosynthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a byproduct of metabolism.
In summary, Glutathione, in the form of reduced GSH, is the most potent anti-oxidant in the human body and is the best anti-toxin and antiviral agent we carry and make – kids with ASD or autism cannot make the reduced form, nor can people with MTHFR or who have copper toxicity. So make sure you stock up!