Gluta Final

8/3/2019 Gluta Final

1/22

GLUTATHIONE


2/22

IUPAC name(2S )-2-amino-4-{[(1 R )-1-

[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid


3/22

Three peptides that make upglutathione

Glutamine Cysteine Glycine


4/22

Glutathione (GSH) is a tripeptide that is anantioxidant, preventing damage toimportant cellular components caused byreactive oxygen species such as freeradicals and peroxides.


5/22

Glutathione reduces disulfide bonds formedwithin cytoplasmic proteins to cysteines byserving as an electron donor.

In the process, glutathione is converted to itsoxidized form glutathione disulfide (GSSG),also called L(-)-Glutathione .


6/22

Glutathione is found almost exclusively in itsreduced form, since the enzyme that reverts itfrom its oxidized form, glutathione reductase ,is constitutively active and inducibleupon oxidative stress.

In fact, the ratio of reduced glutathione tooxidized glutathione within cells is often usedas a measure of cellular toxicity .


7/22

Biosynthesis


8/22

Glutathione is synthesized in two

ATP-dependent steps:1. gamma -glutamylcysteine is synthesized from L-

glutamate and cysteine via the enzyme gamma-

glutamylcysteine synthetase (a.k.a. glutamatecysteine ligase, GCL). This reaction is the rate-limiting step in glutathione synthesis.

2. glycine is added to the C-terminal of gamma -glutamylcysteine via the enzyme glutathionesynthetase.


9/22

Function


10/22

It is the major endogenous antioxidantproduced by the cells , participating directly inthe neutralization of free radicals and reactive

oxygen compounds, as well as maintainingexogenous antioxidants such as vitamins C andE in their reduced (active) forms.

Regulation of the nitric oxide cycle , which iscritical for life but can be problematic if unregulated


11/22

Through direct conjugation, it detoxifies many

xenobiotics (foreign compounds) and carcinogens,both organic and inorganic . This includes heavymetals such as mercury, lead, and arsenic.

It is essential for the immune system to exert its fullpotential , e.g., (1) modulating antigen presentationto lymphocytes, thereby influencing cytokineproduction and type of response (cellular orhumoral) that develops, (2) enhancing proliferationof lymphocytes, thereby increasing magnitude of response, (3) enhancing killing activity of cytotoxic Tcells and NK cells, and (4) regulating apoptosis,thereby maintaining control of the immuneresponse. [


12/22

It plays a fundamental role in numerousmetabolic and biochemical reactions such asDNA synthesis and repair, protein synthesis,prostaglandin synthesis, amino acid transport,and enzyme activation. Thus, every system inthe body can be affected by the state of the

glutathione system, especially the immunesystem, the nervous system, thegastrointestinal system and the lungs.


13/22

Supplementation


14/22

Raising GSH levels through directsupplementation of glutathione is difficult.

Research suggests that glutathione takenorally is not well absorbed across thegastrointestinal tract.

In a study of acute oral administration of avery large dose (3 grams) of oral glutathione,Witschi and coworkers found "it is notpossible to increase circulating glutathione toa clinically beneficial extent by the oraladministration of a single dose of 3 g of glutathione."


15/22

Glutathione is a tightly regulated intracellularconstituent, and is limited in its production bynegative feedback inhibition of its ownsynthesis through the enzyme gamma-glutamylcysteine synthetase , thus greatlyminimizing any possibility of overdosage.


16/22

Pathology


17/22

Excess glutamate at synapses, which may bereleased in conditions such as traumatic braininjury, can prevent the uptake of cysteine, anecessary building-block of glutathione.Without the protection from oxidative injuryafforded by glutathione, cells may be

damaged or killed.


18/22

Methods to determineglutathione


19/22

Reduced glutathione may be visualizedusing Ellman's reagent or bimane derivatessuch as monobromobimane.


20/22

Summary

Glutathione is. It is a tripeptide composed of the amino acids

glutamic acid, cysteine and glycine.

Glutathione is found in all cells in the body,including the bile, the epithelial lining fluid of the lungs, and at much smaller concentrationsin the blood. Glutathione is the most powerfulnaturally occurring antioxidant in all humancells.


21/22

The highest concentration of glutathione is foundin the liver, making it critically important in thedetoxification and elimination of free radicals.Accumulation of these dangerous compoundscan result in oxidative stress, which occurs whenthe generation of free radicals in the bodyexceeds the bodys ability to neutralize andeliminate them. Free radicals are highly reactive

compounds created in the body during normalmetabolic functions; they can also enter the bodythrough the environment.


22/22

Metabolically, glutathione has many functions.For example, glutathione plays a substantialrole in the functioning of the bodys immunesystem. Its antioxidant property makes it vitalto white blood cells (lymphocytes) as itallows them to reach their full potential

during the oxygen-requiring activity of thebodys immune response.

Documents

Gluta Final