Definition
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Glutathione (GSH) - reduced glutathione - is a tripeptide with a gamma peptide linkage between the amine group of cysteine (which is attached by normal peptide linkage to a glycine) and the carboxyl group of the glutamate side-chain. It is an antioxidant, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides. [Wikipedia]
Description
Glutathione is a compound synthesized from cysteine, perhaps the most important member of the body's toxic waste disposal team. Like cysteine, glutathione contains the crucial thiol (-SH) group that makes it an effective antioxidant. There are virtually no living organisms on this planet-animal or plant whose cells don't contain some glutathione. Scientists have speculated that glutathione was essential to the very development of life on earth. Glutathione has many roles; in none does it act alone. It is a coenzyme in various enzymatic reactions. The most important of these are redox reactions, in which the thiol grouping on the cysteine portion of cell membranes protects against peroxidation; and conjugation reactions, in which glutathione (especially in the liver) binds with toxic chemicals in order to detoxify them. Glutathione is also important in red and white blood cell formation and throughout the immune system. glutathione's clinical uses include the prevention of oxygen toxicity in hyperbaric oxygen therapy, treatment of lead and other heavy metal poisoning, lowering of the toxicity of chemotherapy and radiation in cancer treatments, and reversal of cataracts. Glutathione participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate. GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by acetaminophen, that becomes toxic when GSH is depleted by an overdose (of acetaminophen). Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein thiol groups which would otherwise be covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and renew the usable GSH pool. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
Top Gene Interactions
Related Pathways
Glutathione Health Effects
General Information
- Uses/Sources:
For nutritional supplementation, also for treating dietary shortage or imbalance
- Route of Exposure:
Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: ORL-MUS LD<sub>50</sub> 5000 mg/kg, IPR-MUS LD<sub>50</sub> 4020 mg/kg, SCU-MUS LD<sub>50</sub> 5000 mg/kg, IVN-RBT LD<sub>50</sub> > 2000 mg/kg, IMS-MUS LD<sub>50</sub> 4000 mg/kg
Mechanism of Action
| Target Name | Mechanism of Action | References |
|---|---|---|
|
Glutathione peroxidase 1 Glutathione peroxidase 2 Glutathione peroxidase 3 Phospholipid hydroperoxide glutathione peroxidase, mitochondrial Epididymal secretory glutathione peroxidase Glutathione peroxidase 6 Glutathione peroxidase 7 Cytochrome P450 3A4 Probable glutathione peroxidase 8 Glutathione S-transferase P Glutathione S-transferase Mu 2 Glutathione S-transferase A1 Glutathione S-transferase A2 Glutathione S-transferase A3 Glutathione S-transferase Mu 4 Glutathione S-transferase A5 Glutathione S-transferase kappa 1 Glutathione S-transferase Mu 1 Glutathione S-transferase Mu 3 Glutathione S-transferase Mu 5 Glutathione S-transferase omega-1 Glutathione S-transferase omega-2 Glutathione S-transferase theta-1 Microsomal glutathione S-transferase 1 Microsomal glutathione S-transferase 2 Microsomal glutathione S-transferase 3 Maleylacetoacetate isomerase Glutathione S-transferase A4 Matrix metalloproteinase-9 Lactoylglutathione lyase Glutathione synthetase Leukotriene C4 synthase Hematopoietic prostaglandin D synthase Thioredoxin domain-containing protein 12 S-formylglutathione hydrolase Gamma-glutamyltranspeptidase 1 Glutaredoxin-1 Hydroxyacylglutathione hydrolase, mitochondrial Glutathione peroxidase Glutaredoxin-2, mitochondrial Thyrotropin receptor Glutathione reductase, mitochondrial |
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