Systems Biology at Washington University

FIBR

Glutathione

glutathione

By Jeff Cameron

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine) is the most abundant soluble redox buffer in the cell. Glutathione pools help maintain the appropriate redox environment in the cell. Oxidative stress can result in the oxidation of reduced glutathione (GSH) to glutathione disulfide (GSSG). GSH can then be regenerated enzymatically or synthesized de novo. GSH can also be oxidized to form mixed disulfides with various target proteins to alter their activity or as a protective mechanism. Xenobiotics and toxins can be conjugated to glutathione and subsequently degraded or sequestered. The cellular levels of glutathione are in the mM range, with the reduced form (GSH) being the major constituent. The redox potential of the GSH/GSSG couple can provide a good estimate of the redox environment of the cell.

By Jeff Cameron

Glutathione synthesis is comprised of two ATP dependent steps. Glutamate-cysteine ligase catalyzes the formation of a non-conventional peptide linkage of glutamate and cysteine. The addition of glycine to form glutathione is catalyzed by glutathione synthetase. GSH can be oxidized to GSSG and subsequently reduced via glutathione reductase. Proteins in Synechocystis are boxed. There is no annotated glutathione reductase in Synechocystis, however, slr1849 (merA) has the highest amino acid identity. We are currently in the process of generating mutants in each step of the pathway in Synechocystis. Phenotypic analysis of the mutants will provide information on the roles of glutathione in the cell.

By Jeff Cameron