GSTA4
Encyclopedia
Glutathione S-transferase A4, also known as GSTA4, is an enzyme
which in humans is encoded by the GSTA4 gene
.
are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase
activity that function in the detoxification of lipid peroxidation products.
GSTA4 shows very high activity with reactive carbonyl compounds such as alk-2-enals. GSTA4 is highly effective in catalyzing the conjugate addition
of reduced glutathione
to 4-hydroxynonenal
, an important product of peroxidative degradation of arachidonic acid
and a commonly used biomarker for oxidative damage in tissue.
, Alzheimer's disease
, cataract
formation, and atherosclerosis
hence reduced expression of the GSTA4 enzyme may have pathophysiological
consequences. The expression of this gene is decreased drastically among burn and trauma victims.
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...
which in humans is encoded by the GSTA4 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Cytosolic and membrane-bound forms of glutathione S-transferaseGlutathione S-transferase
Enzymes of the glutathione S-transferase family are composed of many cytosolic, mitochondrial, and microsomal proteins. GSTs are present in eukaryotes and in prokaryotes, where they catalyze a variety of reactions and accept endogenous and xenobiotic substrates.GSTs can constitute up to 10% of...
are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase
Glutathione peroxidase
Glutathione peroxidase is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage...
activity that function in the detoxification of lipid peroxidation products.
GSTA4 shows very high activity with reactive carbonyl compounds such as alk-2-enals. GSTA4 is highly effective in catalyzing the conjugate addition
Nucleophilic conjugate addition
Nucleophilic conjugate addition is a type of organic reaction. Ordinary nucleophilic additions or 1,2-nucleophilic additions deal mostly with additions to carbonyl compounds. Simple alkene compounds do not show 1,2 reactivity due to lack of polarity, unless the alkene is activated with special...
of reduced 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...
to 4-hydroxynonenal
4-Hydroxynonenal
4-Hydroxynonenal, or 4-hydroxy-2-nonenal or 4-HNE or HNE, , is an α,β-unsaturated hydroxyalkenal which is produced by lipid peroxidation in cells...
, an important product of peroxidative degradation of arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
and a commonly used biomarker for oxidative damage in tissue.
Clinical significance
Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's diseaseParkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
formation, and atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
hence reduced expression of the GSTA4 enzyme may have pathophysiological
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
consequences. The expression of this gene is decreased drastically among burn and trauma victims.