Glutathione transferases, regulators of cellular metabolism and physiology

• Published in: Biochimica et biophysica acta Vol. 1830; no. 5; pp. 3267 - 3288
• Main Authors: Board, Philip G., Menon, Deepthi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2013
• Subjects: Animals; Biotransformation; Catalysis; cell proliferation; Cytosol - metabolism; genetics; glutathione; Glutathione - genetics; Glutathione - metabolism; glutathione peroxidase; Glutathione transferase; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Humans; isomerization; metabolism; muscles; myocardium; phosphotransferases (kinases); prostaglandins; ryanodine receptors; Signal Transduction; steroid hormones; thiols; tyrosine; xenobiotics; Xenobiotics - metabolism; Xenobiotics - pharmacokinetics; Glutathione transferase
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.11.019

The cytosolic glutathione transferases (GSTs) comprise a super family of proteins that can be categorized into multiple classes with a mixture of highly specific and overlapping functions. The review covers the genetics, structure and function of the human cytosolic GSTs with particular attention to their emerging roles in cellular metabolism. All the catalytically active GSTs contribute to the glutathione conjugation or glutathione dependant-biotransformation of xenobiotics and many catalyze glutathione peroxidase or thiol transferase reactions. GSTs also catalyze glutathione dependent isomerization reactions required for the synthesis of several prostaglandins and steroid hormones and the catabolism of tyrosine. An increasing body of work has implicated several GSTs in the regulation of cell signaling pathways mediated by stress-activated kinases like Jun N-terminal kinase. In addition, some members of the cytosolic GST family have been shown to form ion channels in intracellular membranes and to modulate ryanodine receptor Ca2+ channels in skeletal and cardiac muscle. In addition to their well established roles in the conjugation and biotransformation of xenobiotics, GSTs have emerged as significant regulators of pathways determining cell proliferation and survival and as regulators of ryanodine receptors that are essential for muscle function. This article is part of a Special Issue entitled Cellular functions of glutathione. ► Glutathione transferases are known for their capacity to conjugate xenobiotics. ► Glutathione transferases isomerize intermediates in steroid hormone synthesis. ► Zeta class glutathione transferases catalyze a required step in tyrosine catabolism. ► Several glutathione transferases regulate signaling pathways through JNK. ► Some members of the GST family form and modulate ion channels.