ABSTRACT
Glutathione (GSH) plays a highly complex role in eicosanoid metabolism being a cofactor of terminal prostaglandin synthases and a substrate for leukotriene synthases, modulating enzyme activities, contributing to transcriptional activation, silencing key enzymes such as cyclooxygenases and lipoxygenases, as well as protecting related enzymes from oxidative inactivation. In human polymorphonuclear leukocytes, deprivation of GSH or the decrease of glutathione peroxidase activity by selenium deprivation dramatically increased 5-lipoxygenase activity. The sculpting of lipid peroxidation products to specific physiological mediators during evolution involved recruitment of GSH-dependent processes at various stages. The membrane-associated proteins in eicosanoid and glutathione metabolism family to which microsomal glutathione transferase 1 belongs, contains six members. Hematopoietic prostaglandin D synthase is a GSH-dependent enzyme belonging to the cytosolic glutathione transferase Sigma family. Lipocalin-type Prostaglandin D synthase is not strictly dependent on GSH, accepting various other thiols. GSH concentrations in cells can exhibit diurnal variation as well as vary across the cell cycle.
