Glutathione

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Glutathione
2D structure for Glutathione
Chemical Name	(2S)-2-amino-4-[[(1R)-1-(carboxymethylcarbamoyl)-2-sulfanyl-ethyl]carbamoyl]butanoic acid
Chemical Formula	C₁₀H₁₇N₃O₆S
CAS Number	70-18-8
Chemical Information	HMDB00125
Biochemical Taxonomy	Peptides
Functional Taxonomy	Not Available
Nutritional Taxonomy	Not Available
Metabolic Pathways	Alanine and Aspartate Metabolism Arginine and D-Ornithine Metabolism Glutathione Metabolism Glycine, Serine and Threonine Metabolism Lysine Degradation One Carbon Pool by Folate Purine Metabolism
Biofluid Location	Blood Cellular Cytoplasm Cerebrospinal Fluid (CSF) Urine
Tissue Location	All Tissues
Normal Biofluid Concentrations	Blood: 1090.0 +/- 200.0 uM Blood: 37.03 +/- 4.76 umol/L Cellular Cytoplasm: 3210 (1710-4710) uM Cerebrospinal Fluid (CSF): 1.2 +/- 0.16 uM Urine: 0.065 umol/mmol creatinine
Normal Tissue Concentrations	Not Available
Diseases / Conditions Related to Nutrition	Multiple Sclerosis Multiple Sclerosis under treatment with Acetyl-L-carnitine Patients with Canavan disease Traumatic Brain Injury
Other (Monogenic Disorders)	Not Available
Abnormal Biofluid Concentrations	Blood (Patients with Canavan disease): 30.22 +/- 2.55 umol/L Cerebrospinal Fluid (CSF) (Multiple Sclerosis under treatment with Acetyl-L-carnitine): 4.56 +/- 0.7 uM Cerebrospinal Fluid (CSF) (Multiple Sclerosis): 2.58 +/- 1.2 uM Cerebrospinal Fluid (CSF) (Traumatic Brain Injury): 0.19 +/- 0.05 uM
Abnormal Tissue Concentrations	Not Available
Physiological Processes	Not Available

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Introduction

guidelines
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. (http://www.dcnutrition.com/AminoAcids/) 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. (http://en.wikipedia.org/wiki/glutathione)

Biological Function

guidelines
Glutathione metabolism and transport participates in many cellular reactions including antioxidant defence of the cell, drug detoxification and cell signaling (involved in the regulation of gene expression, apoptosis, and cell proliferation). Reduced glutathione (GSH) catabolism has been reported to modulate redox-sensitive components of signal transduction cascades. Glutathione is required for the conversion of the arachidonic metabolite, prostaglandin H2, into prostaglandins D2 and E2 by endoperoxide isomerase (R. Franco et al. 2007 Pubmed)

Catabolism

guidelines
Reduced glutathione is formed in a two-step enzymatic process including, first, the formation of gamma-glutamylcysteine from glutamate and cysteine, by the activity of gamma-glutamylcysteine synthethase; and second, the formation of GSH by the activity of GSH synthetase which uses gamma-glutamylcysteine and glycine as substrates. While its synthesis and metabolism occurs intracellularly, its catabolism occurs extracellularly by a series of enzymatic and plasma membrane transport steps. Plasma concentrations of glutathione are relatively mainly because of its rapid catabolism. Intracellular GSH can exist as a monomer in its reduced form, or as a disulfide dimmer formed due to its oxidation (GSSG) which usually accounts for less than 1% of the total intracellular glutathione content (Franco R et al. 2007 Pubmed).