Detoxifying action of GSH through the mercapturic pathway. X is a compound with an electrophilic center that can form GSH conjugate in a reaction catalyzed by GSH S-transferase. The γ-glutamyl moiety is then cleaved by γ-glutamyltranspeptidase, releasing the cysteinyl-glycine conjugate. This is further broken down by dipeptidase, resulting in the formation of the cysteinyl conjugate. This is followed by N-acetylation of the cysteine conjugate catalyzed by N-acetylase, forming a mercapturic acid.

GSH as cysteine storage via the γ-glutamyl cycle. The γ-glutamyl cycle utilize GSH as a continuous source of cysteine. Cysteine is taken up readily by most cells and once it enters the cell, most of it is incorporated into GSH while the rest is incorporated into newly synthesized proteins and/or broken down into sulfate and taurine. GSH is exported from the cell and the ecto-enzyme GGT then transfers the γ-glutamyl moiety of GSH to an amino acid (the best acceptor being cystine), forming γ-glutamyl amino acid and cysteinylglycine. The γ-glutamyl amino acid can then be transported back into the cell to complete the cycle. Once inside the cell, the γ-glutamyl amino acid can be further metabolized to release the amino acid and 5-oxoproline, which can be converted to glutamate. Cysteinylglycine is broken down by dipeptidase (DP) to generate cysteine and glycine, which are then transported back into the cell to be reincorporated into GSH.

Structure of GSH or γ-glutamylcysteinyl glycine, where the N-terminal glutamate and cysteine are linked by the γ-carboxyl group of glutamate.

GSH is an important antioxidant. Hydrogen peroxide, generated as a result of aerobic metabolism, can be metabolized by GSH peroxidase in the cytosol and mitochondria, and by catalase in the peroxisome. GSSG that is formed is reduced back to GSH by GSSG reductase at the expense of NADPH, thereby forming a redox cycle. Organic peroxides (ROOH) can be reduced by either GSH peroxidase or GSH S-transferase. Under severe oxidative stress, the ability of the cell to reduce GSSG to GSH may be overcome, leading to an accumulation of GSSG. To avoid a shift in the redox equilibrium, GSSG can either be actively transported out of the cell or react with a protein sulfhydryl (PSH) to form a mixed disulfide (PSSG).

Hepatic methionine metabolism and GSH synthesis. Up to half of the daily intake of methionine (Met) is catabolized to S-adenosylmethionine (SAMe) in the liver in a reaction catalyzed by methionine adenosyltransferase (MAT). SAMe is the link to three key metabolic pathways - polyamine synthesis, transmethylation and transsulfuration. Polyamine synthesis is required for cell growth and here SAMe is decarboxylated and the remaining propylamino moiety is donated to putrescine and spermidine. In transmethylation, SAMe donates its methyl group to a large variety of acceptor molecules in reactions catalyzed by methyltransferases (MTs). S-adenosylhomocysteine (SAH), generated as a result of transmethylation, is a potent inhibitor of all transmethylation reactions. Hydrolysis of SAH to homocysteine (Hcy) and adenosine is through a reversible reaction catalyzed by SAH hydrolase, whose thermodynamics favors biosynthesis rather than hydrolysis. In vivo this reaction proceeds as hydrolysis because the products Hcy and adenosine are promptly removed. Hcy can be remethylated to form methionine via methionine synthase (MS), which requires folate and vitamin B₁₂ and betaine homocysteine methyltransferase (BHMT), which requires betaine. MS-mediated homocysteine remethylation requires 5-methyltetrahydrofolate (5-MTHF), which is generated from 5,10-methylenetetrahydrofolate (5,10-MTHF) in a reaction catalyzed by methylenetetrahydrofolate reductase. 5-MTHF is then converted to tetrahydrofolate (THF) as it donates its methyl group and THF is converted back to 5,10-MTHF. In trans-sulfuration, Hcy is converted to cysteine (Cys), the rate-limiting precursor for GSH, via a two-step enzymatic process catalyzed by cystathionine β-synthase (CBS) and cystathionase, both requiring vitamin B₆. Cys is then converted to GSH. The trans-sulfuration pathway is particularly active in the liver and allows methionine and SAMe to be effectively utilized as GSH precursor.