Glutathione S-Transferase Alpha 4 (GSTA4) is an enzyme encoded by the GSTA4 gene in humans. It belongs to the family of glutathione S-transferases (GSTs), which are crucial for cellular detoxification processes. These enzymes catalyze the conjugation of reduced glutathione to a variety of hydrophobic and electrophilic compounds, aiding in their detoxification and excretion .
The GSTA4 gene is located on chromosome 6 and is part of the alpha class of GSTs. This class of enzymes is characterized by their glutathione peroxidase activity, which is essential for detoxifying lipid peroxidation products . The GSTA4 protein is a homodimer, meaning it consists of two identical subunits, and it exhibits high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE) .
GSTA4 plays a significant role in protecting cells from oxidative stress by detoxifying reactive electrophiles produced during oxidative metabolism. These reactive electrophiles have been linked to various degenerative diseases, including Parkinson’s disease, Alzheimer’s disease, cataract formation, and atherosclerosis . The enzyme’s ability to conjugate reduced glutathione to harmful compounds makes it a vital component of the cellular defense mechanism .
Mutations or alterations in the GSTA4 gene have been associated with several diseases. For instance, GSTA4 is linked to osteogenesis imperfecta type IV and cataracts . The enzyme’s role in detoxifying lipid peroxidation products also implicates it in conditions related to oxidative stress and inflammation .
Recombinant human GSTA4 is produced using recombinant DNA technology, which involves inserting the human GSTA4 gene into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant enzyme is used in various research and clinical applications, including studies on detoxification mechanisms, drug metabolism, and the development of therapeutic interventions for diseases associated with oxidative stress .