GSTA1

GSTA1 Full Name

glutathione S-transferase alpha 1

GSTA1 Introduction

GSTA1 encodes a cytosolic enzyme belonging to the alpha class of the glutathione S-transferase (GST) superfamily, a group of multifunctional phase II detoxification enzymes that catalyze the conjugation of glutathione (GSH) to a wide variety of electrophilic substrates. GSTA1 is predominantly expressed in the liver, kidney, and small intestine, where it serves as a principal defense against endogenous and exogenous toxic compounds, including carcinogens, environmental pollutants, reactive oxygen species byproducts, and therapeutic drugs. Beyond its canonical conjugation activity, GSTA1 also exhibits glutathione peroxidase activity, directly reducing lipid hydroperoxides, and participates in the metabolism of prostaglandins such as PGA2 and PGJ2, thereby influencing inflammatory signaling. The enzyme functions as a homodimer and its catalytic mechanism involves a GSH-binding site (G-site) and a hydrophobic substrate-binding site (H-site), which together facilitate nucleophilic attack by the thiol group of glutathione on electrophilic substrates. Additionally, GSTA1 participates in intracellular signaling by physically interacting with kinases such as ASK1 and JNK, sequestering them in an inactive complex and thereby modulating stress-responsive MAPK pathways.

Figure 1. A schematic diagram depicting the mechanism of GSTA1 in hepatic steatosis. (Source: Jiang J, et al. 2024)

The clinical significance of GSTA1 is prominently observed in oncology, where its overexpression has been linked to chemotherapeutic resistance. In hepatocellular carcinoma, elevated GSTA1 expression promotes cisplatin resistance by enhancing drug efflux and detoxification, making GST inhibition an attractive strategy for sensitizing tumors to platinum-based chemotherapy. Paradoxically, GSTA1 has also been reported to suppress tumor progression and predict favorable prognosis in certain primary hepatocellular carcinoma subsets, suggesting context-dependent roles that may vary with tumor stage and microenvironment. Genetic polymorphisms in GSTA1, particularly promoter variants affecting expression levels, have been associated with differential susceptibility to various cancers and drug-induced toxicity. In non-malignant disease, reduced GSTA1 activity has been implicated in liver injury, chronic inflammatory conditions, and neurodegenerative disorders where oxidative stress plays a pathogenic role. These findings underscore GSTA1's dual identity as both a detoxification guardian and a determinant of therapeutic response.

Alternate Names for GSTA1

GSTA1; glutathione S-transferase alpha 1; GST2; GTH1; GSTA1-1; glutathione S-transferase A1; GST-epsilon; GST HA subunit 1; GST, class alpha, 1; GST class-alpha member 1

• 1. Jiang J, et al. Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1. Int J Mol Sci. 2024 May 7;25(10):5086.
  2. Sau A, et al. Glutathione transferases and development of new principles to overcome drug resistance. Arch Biochem Biophys. 2010 Aug 15;500(2):116-22.