Practice question

Glutathione is a low-molecular-weight tripeptide gamma-glutamyl-cysteinyl-glycine present at millimolar concentrations up to 10 mM in many Gram-negative bacteria such as Escherichia coli and few Gram-positives that synthesize it via GshA and GshB. Reduced form GSH serves as major thiol buffer and electron donor protecting against reactive oxygen species generated continuously by endogenous respiratory electron transport and by host immune oxidative burst involving NADPH oxidase-dependent production of superoxide during phagocytosis. It directly scavenges superoxide anion, hydroxyl radical and hydrogen and organic peroxides via glutathione peroxidases, forming oxidized glutathione disulfide GSSG that is rapidly recycled by NADPH-dependent glutathione reductase Gor maintaining high GSH to GSSG ratio of greater than 100 to 1. GSH also forms mixed disulfides with redox-sensitive cysteine residues in proteins via reversible S-glutathionylation, temporarily shielding them from irreversible overoxidation to sulfinic or sulfonic acids that require repair. It acts as cofactor for glutathione peroxidases, glyoxalases that detoxify methylglyoxal, and for detoxification of electrophiles and xenobiotics via glutathione S-transferases. Depletion via mutation in gshA renders cells hypersensitive to oxidants, linking its primary role to redox homeostasis rather than to DNA replication or flagellar motility.