Glutathione peroxidase
Overview
 
Glutathione peroxidase (GPx) is the general name of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 family with peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...

 activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 hydroperoxides
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...

 to their corresponding alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

s and to reduce free hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 to water.
There are several isozymes encoded by different genes, which vary in celullar location and substrate specificity.
Encyclopedia
Glutathione peroxidase (GPx) is the general name of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 family with peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...

 activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 hydroperoxides
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...

 to their corresponding alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

s and to reduce free hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

 to water.

Isozymes

There are several isozymes encoded by different genes, which vary in celullar location and substrate specificity. Glutathione peroxidase 1
GPX1
Glutathione peroxidase 1 is an enzyme that in humans is encoded by the GPX1 gene.-Further reading:...

  (GPx1) is the most abundant version, found in the cytoplasm of nearly all mammalian tissues, whose preferred substrate is hydrogen peroxide. Glutathione peroxidase 4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

 (GPx4) has a high preference for lipid hydroperoxides; it is expressed in nearly every mammalian cell, though at much lower levels. Glutathione peroxidase 2
GPX2 (gene)
Glutathione peroxidase 2 is an enzyme that in humans is encoded by the GPX2 gene.The antioxidant enzyme glutathione peroxidase 2 is one out of eight known glutathione peroxidases in humans...

  is an intestinal and extracellular enzyme, while glutathione peroxidase 3 is extracellular, especially abundant in plasma. So far, eight different isoforms of glutathione peroxidase (GPx1-8) have been identified in humans.
Gene Locus Enzyme
GPX1
GPX1
Glutathione peroxidase 1 is an enzyme that in humans is encoded by the GPX1 gene.-Further reading:...

 
Chr. 3 p21.3 glutathione peroxidase 1
GPX2
GPX2 (gene)
Glutathione peroxidase 2 is an enzyme that in humans is encoded by the GPX2 gene.The antioxidant enzyme glutathione peroxidase 2 is one out of eight known glutathione peroxidases in humans...

 
Chr. 14 q24.1 glutathione peroxidase 2 (gastrointestinal)
GPX3
GPX3
Glutathione peroxidase 3 , also known as plasma glutathione peroxidase or extracellular glutathione peroxidase is an enzyme that in humans is encoded by the GPX3 gene....

 
Chr. 5 q23 glutathione peroxidase 3 (plasma)
GPX4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

 
Chr. 19 p13.3 glutathione peroxidase 4 (phospholipid hydroperoxidase)
GPX5
GPX5
Glutathione peroxidase 5 , also known as epididymal secretory glutathione peroxidase is an enzyme that in humans is encoded by the GPX5 gene....

 
Chr. 6 p21.32 glutathione peroxidase 5 (epididymal androgen-related protein)
GPX6
GPX6
Glutathione peroxidase 6 is an enzyme that in humans is encoded by the GPX6 gene.This gene product belongs to the glutathione peroxidase family, which functions in the detoxification of hydrogen peroxide. It contains a selenocysteine residue at its active site. The selenocysteine is encoded by...

 
Chr. 6 p21 glutathione peroxidase 6 (olfactory)
GPX7
GPX7
Glutathione peroxidase 7 is an enzyme that in humans is encoded by the GPX7 gene.-Further reading:...

 
Chr. 1 p32 glutathione peroxidase 7
GPX8
GPX8
Glutathione peroxidase 8 is an enzyme that in humans is encoded by the GPX8 gene. GPx-8 is a member of the glutathione peroxidase family....

 
Chr. 5 q11.2 glutathione peroxidase 8 (putative)

Reaction

An example reaction that glutathione peroxidase catalyzes is:
2GSH + H2O2 → GS–SG + 2H2O,


where GSH represents reduced monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...

ic glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, and GS–SG represents glutathione disulfide
Glutathione disulfide
Glutathione disulfide is a disulfide derived from two glutathione molecules.In living cells, glutathione disulfide is reduced into two molecules of glutathione with reducing equivalents from the coenzyme NADPH. This reaction is catalyzed by the enzyme glutathione reductase...

.

Glutathione reductase
Glutathione reductase
Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....

 then reduces the oxidized glutathione to complete the cycle:
GS–SG + NADPH
Nicotinamide adenine dinucleotide phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or TPN in older notation , is a coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....

 + H+ → 2 GSH + NADP+.

Structure

Mammalian GPx1
GPX1
Glutathione peroxidase 1 is an enzyme that in humans is encoded by the GPX1 gene.-Further reading:...

, GPx2
GPX2 (gene)
Glutathione peroxidase 2 is an enzyme that in humans is encoded by the GPX2 gene.The antioxidant enzyme glutathione peroxidase 2 is one out of eight known glutathione peroxidases in humans...

, GPx3, and GPx4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

 have been shown to be selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

-containing enzymes, whereas GPx6 is a selenoprotein
Selenoprotein
In molecular biology a selenoprotein is any protein that includes a selenocysteine amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases and three thioredoxin reductases, which both contain only one Se-Cys. Selenoprotein P is the most common...

 in humans with cysteine-containing homologues in rodents. GPx1, GPx2, and GPx3 are homotetrameric proteins, whereas GPx4 has a monomeric structure. As the integrity of the cellular and subcellular membranes depends heavily on glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 peroxidase, the antioxidative
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

 protective system of glutathione peroxidase itself depends heavily on the presence of selenium.

Reaction mechanism

The mechanism is at the selenocysteine
Selenocysteine
Selenocysteine is an amino acid that is present in several enzymes .-Nomenclature:...

 site, which is in a Se(-) form as resting state. This is oxidized by the peroxide to SeOH, which then reacts with a GSH molecule to form GS-Se and water, and then by another GSH molecule to from Se(-) again, releasing GS-SG as the by-product.

Species distribution

Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are grossly phenotypically normal and have a normal lifespan, indicating that this enzyme is not critical for life. However, Gpx1 -/- mice develop cataracts at an early age and exhibit defects in muscle satellite cell proliferation.

However, glutathione peroxidase 4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

 knockout mice die during early embryonic development.

There is some evidence that reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.

No information is available on knockouts of the other isozymes.

The bovine erythrocyte enzyme has a molecular weight of 84 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...

.
Role in disease=

Genetic polymorphisms in glutathione peroxidase enzymes and their altered expressions and activities are associated with oxidative DNA damage and, as a result, the individual’s risk of cancer susceptibility.

Human proteins containing this domain

GPX1
GPX1
Glutathione peroxidase 1 is an enzyme that in humans is encoded by the GPX1 gene.-Further reading:...

; GPX2
GPX2 (gene)
Glutathione peroxidase 2 is an enzyme that in humans is encoded by the GPX2 gene.The antioxidant enzyme glutathione peroxidase 2 is one out of eight known glutathione peroxidases in humans...

; GPX3
GPX3
Glutathione peroxidase 3 , also known as plasma glutathione peroxidase or extracellular glutathione peroxidase is an enzyme that in humans is encoded by the GPX3 gene....

; GPX4
GPX4
Glutathione peroxidase 4, also known as GPX4, is an enzyme that in humans is encoded by the GPX4 gene. GPX4 is a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation.- Function :...

; GPX5
GPX5
Glutathione peroxidase 5 , also known as epididymal secretory glutathione peroxidase is an enzyme that in humans is encoded by the GPX5 gene....

;

See also

  • Glutathione reductase
    Glutathione reductase
    Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....

  • Selenium deficiency
    Selenium deficiency
    Selenium deficiency is relatively rare in healthy well-nourished individuals. Few cases have been reported.-Causes:It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, those who have had gastrointestinal bypass surgery, and also on...

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