GSH

Glutathione (GSH) is a tripeptide consisting of glutamate, cysteine, and glycine. In cells it largely exists in the reduced form (GSH) and can be oxidized to the disulfide form (GSSG). It is the most abundant intracellular antioxidant and a central mediator of redox homeostasis.

Biology and biosynthesis: GSH is synthesized in the cytosol by two ATP-dependent enzymes: gamma-glutamylcysteine synthetase (also called GCL) combines glutamate and cysteine to form gamma-glutamylcysteine; glutathione synthetase adds glycine to form GSH. The first step is rate-limiting and regulated by GSH levels. Cysteine availability commonly limits synthesis. GSH is regenerated from GSSG by glutathione reductase using NADPH.

Functions: as an antioxidant, GSH detoxifies reactive oxygen species and maintains thiol groups in proteins. It participates in phase II metabolism via glutathione S-transferases, forming GSH conjugates that are excreted. The GSH/GSSG ratio reflects cellular redox state. Extracellular GSH participates in amino acid transport via the gamma-glutamyl cycle, and GGT participates in GSH metabolism outside cells.

Distribution and clinical notes: GSH is abundant in liver, but present in nearly all tissues; intracellular concentrations are typically millimolar. Depletion of GSH is associated with oxidative stress and is implicated in aging and neurodegenerative diseases, liver disease, and cancer. Direct GSH supplementation has limited bioavailability; precursors such as N-acetylcysteine are commonly used to boost stores.

Measurement and research: GSH levels can be assayed by DTNB-based methods, HPLC, or mass spectrometry. In research and clinical contexts, GSH status is used as a biomarker of oxidative stress.