glutathionStransferázy

GlutathionStransferázy, commonly known as glutathione S-transferases (GSTs), are a diverse family of enzymes involved in detoxification. They catalyze the conjugation of the tripeptide glutathione (GSH) to a wide range of electrophilic compounds, including products of oxidative stress and xenobiotics, increasing their water solubility and facilitating excretion.

GSTs are organized into cytosolic, microsomal (MAPEG family), and mitochondrial classes. Cytosolic GSTs predominate in most tissues and are divided into several subclasses (GSTA, GSTM, GSTP, GSTT, GSTZ, GSTK, etc.). Microsomal GSTs (MGSTs) are membrane-associated enzymes, while mitochondrial GSTs form a distinct subset with specialized roles.

Mechanism and structure: The reaction uses GSH as a cofactor; the enzyme activates the thiolate form of GSH to enable nucleophilic attack on electrophiles. Most cytosolic GSTs are homodimers (~50–60 kDa total) with each subunit ~25–28 kDa, comprising an N-terminal thioredoxin-like domain and a C-terminal all-α-helical domain. Active site residues vary by class, including serine, tyrosine, or cysteine, reflecting functional diversity among GSTs.

Genetic and clinical relevance: In humans, common GST genes include GSTM1, GSTT1, and GSTP1. Copy number variations or gene deletions (null alleles) can abolish enzyme activity in individuals. Polymorphisms influence susceptibility to carcinogens, oxidative stress–related diseases, and drug response by altering detoxification of compounds such as polycyclic aromatic hydrocarbons and aflatoxins, and by modulating chemotherapy resistance in some cancers.

Research and applications: GSTs serve as biomarkers of exposure and as targets in pharmacology. In drug development, modulators of GST activity are explored to influence metabolism and resistance, while some GSTs also contribute to cellular redox balance through peroxidase activity.