Glutathione (GSH) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.
GSH Nebraska: general info + transporters
Tissue distribution and concentration
2-5 mM according to the tissue
GSH half life
It ranges from 3/5 hours to 30/50 hours
If we assume 40kg tissues with an average 2.5 mM GSH (ca 750 mg/l) it means 30 g GSH in the whole body with an half-life of 48hours its life is around 10 days. 3 g. GSH a day.ca 1.5 g. glutamate a day.
Glutamate is produced in the human body and plays an essential role in metabolism.
Almost two kilograms (about four pounds) of naturally occurring glutamate are found in muscles, in the brain, in kidneys, in the liver and in other organs and tissues.
The monosodium glutamate added to foods to improve taste represents only a small amount of the total glutamate present in most foods. For example, the average daily amount of glutamate consumed in bound form as protein from food is about 15 grams. In addition, about 1 gram of free glutamate in food would also be consumed during the same day. In contrast, average daily intake of added monosodium glutamate ranges between 0.5 grams and 3.0 grams a day, dependent upon local dietary customs and cuisine.
h4. Glutamine for Purine biosynthesis
400/800 mg day uric acid
Endogenous Glutathione Conjugates: Occurrence and Biological Functions, 1996
GS amino acid transport
Inviato da iPad
Cellular GSH homeostasis and GSH-dependent reactions. Intracellular GSH balance is maintained by de novo synthesis, regeneration from GSSG, and extracellular GSH uptake. In transport epithelial cells, such as enterocytes, γ -glutamyl transferase ( γ -GT) and dipeptidase (DP) catalyzed the hydrolysis of extracellular GSH to its constituent amino acids, glutamate, cysteine and glycine. Additionally, intestinal epithelial cells can import intact GSH from the lumen via specifi c plasma membrane transporters. Cytosolic synthesis of GSH takes place in two ATP-dependent reactions catalyzed by glutamate-cysteine ligase (GCL) and glutathione synthase (GS). The intracellular GSH pool, present in millimolar concentrations, is involved in various GSH-dependent reactions. Compartmentation of GSH within the mitochondria, nucleus or endoplasmic reticulum creates distinct and independently regulated subcellular redox pools. As part of the antioxidant defence system, GSH participates in conjugation reactions catalyzed by glutathione-S-transferases (GSTs), in the reduction of hydrogen peroxide (H O ) and lipid hydroperoxides (LOOH) catalyzed by glutathione peroxidases (Gpxs), and the reduction 2 2 of protein-disulfi des (PrSSG) catalyzed by glutaredoxins (Grxs). The reduction of glutathione disulfi de (GSSG) by glutathione reductase (GR) in the GSH redox cycle regenerates GSH. GSSG reduction occurs at the expense of NADPH, produced from the pentose phosphate pathway (PPP) from glucose oxidation.
h3. GSH regulation
Glutathione exists in reduced (GSH) and oxidized states. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H++ e-) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG).
Such a reaction is possible due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver ).
GSH can be regenerated from GSSG by the enzyme glutathione reductase.
Protein SS groups reduction and Protein/GSH adducts cleavage
Gssg cholesterol synthesis
cholesterol synthesis and GSSG
Glutathionylation: a regulatory role of glutathione in physiological processes, 2018
Direct and indirect regulatory roles in physiological processes include glutathionylation of:
- major transcriptional factors,
- nitric oxide (NO)
Which is the information content of GSH molecule?
GSH and Aging
GLUTATHIONE AND AGING--METABOLISM AND LIFE SPAN STUDIES 2014
- Abstract Text:
DESCRIPTION (Adapted from the Applicant's Abstract): Glutathione (GSH) is a major antioxidant present in high concentrations in nearly all living cells, with numerous critical functions in cellular homeostasis and defense. The investigator's previous results and those of others suggest that GSH depletion is a general phenomenon of aging tissues and organisms. They hypothesize that the loss of GSH is caused by an impairment in its biosynthesis and represents a key factor in the biological aging process, based upon its essential roles. While considerable data have been accumulated to support the important role for GSH in aging, little information is available regarding the mechanisms responsible for its depletion during aging. The overall goals of the present research proposal are to determine the cause of the GSH deficiency in the aging mouse and to elucidate the mechanisms by which caloric restriction (CR) increases GSH and prevents the aging-deficiency. To this end, they will determine the effects of aging and CR on the metabolism of Met, Cys and GSH in the C57BL/6 mouse model. In addition, they will also examine the effects of specific enhancement and depletion of GSH on longevity, using lifelong feeding with GSH monoethyl ester and buthionine sulfoximine, respectively. A systematic and multi-level approach will be used to assess metabolism. The specific activities of the enzymes involved in GSH, Cys and Met metabolism will be determined along with the levels of specific intermediate metabolites in different tissues. GSH turnover will be assessed on whole animals by injection of radiolabeled precursors. Animals of 4 age groups will be analyzed in order to assess growth and developmental changes as well as aging-specific changes. The results of these studies will provide new information on the biochemical mechanisms of the aging process, which will be important in the development of strategies to enhance health and longevity.
caloric restriction GSH
Curcumin increases total GSH and GSH/GSSG ratio