The INDIVIDUALIST

A Wiki about biochemical individuality

Polymorphism

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Description

The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic.

Polymorphism

Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. The human GSTs are divided into four classes: alpha, mu, pi and theta. Previous studies indicated that the absence of the Glutathione S-Transferase M1 (GSTM1) protein correlated with an increased risk of developing some types of cancers. Association between specific genotype and the development of breast cancer is still an open question.

Genetic polymorphisms of human glutathione S-transferases (hGSTs) have important implications for drug efficacy and cancer susceptibility.

It has recently been shown that the 5' untranslated region of the mRNA and GLCLC contains a GAG trinucleotide repeat polymorphism. It is our hypothesis that this repeat polymorphism influences the rate of transcription or translation of GLCLC, or the stability of its mRNA, ultimately influencing GSH homeostasis and the ability of the lung to respond to the oxidative stress associated with lung inflammation. (1)

Structure of GSTs

Mammalian cytosolic GSTs are homodimeric, and the monomers are in the range of 22-29 kDa. They are active over a wide variety of substrates with considerable overlap.

Glutathione S-transferase and gene fusion

Genetic engineers have used Glutathione S-transferase to create the so-called 'GST gene fusion system'. Here, GST is used to express, purify and detect proteins of interest. In a GST gene fusion system, the GST protein is incorporated into an expression vector alongside the gene sequence encoding the protein of interest. Induction of the vector results in expression of a fusion protein - the protein of interest fused to the GST protein, which can then be released from the cells and purified.

GSTs and Biotransformation

Glutathione S-transferases are considered, among several others, to contribute to the phase II biotransformation of xenobiotics. Drugs, poisons, and other compounds not traditionally listed in either groups are usually somewhat modified by the phase I and/or phase II mechanisms, and finally exreted from the body. GSTs contribute to this type of metabolism by conjugating these compounds (often electrophilic and somewhat lipophilic in nature) with reduced glutathione to facilitate dissolution in the aqueous cellular and extracelluar media, and from there, out of the body.

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