Glutathione: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Glutathione (GSH): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Glutathione is a small molecule made of the three amino acids glutamate, cysteine and glycine. Through the sulfur group of its cysteine it hands hydrogen to peroxides; enzymes also attach it to foreign substances, which are then excreted.

The pathway step by step

1. Homocysteine → Cystathionine CBS · vitamin B6 (PLP), serine Cystathionine β-synthase (CBS) joins homocysteine to serine. The enzyme works with pyridoxal phosphate, the active form of vitamin B6, and also carries a haem group. Source 2
2. Cystathionine → Cysteine CSE · vitamin B6 (PLP) Cystathionine γ-lyase (CSE) splits cystathionine, releasing cysteine. Cysteine also comes from food and is the building block in shortest supply for glutathione production. Source 2, 1
3. Cysteine → γ-glutamylcysteine GCL · glutamate, ATP Glutamate-cysteine ligase (GCL) links glutamate and cysteine through an unusual bond. This step sets the pace of the whole pathway and uses ATP. Source 1
4. γ-glutamylcysteine → Glutathione (GSH) Glutathione synthetase · glycine, ATP Glutathione synthetase adds glycine. The result is glutathione – a small molecule made of glutamate, cysteine and glycine that is present in every cell. Source 1
5. Hydrogen peroxide → Water GPx · selenium Glutathione peroxidases transfer hydrogen from two GSH molecules to hydrogen peroxide, which becomes water. These enzymes carry selenium in their active site. Source 3
6. GSH → GSSG In this reaction, two GSH molecules join via their sulphur atoms to form GSSG, glutathione disulphide. Source 3, 4
7. GSSG → GSH regenerated Glutathione reductase · NADPH, FAD (vitamin B2) Glutathione reductase splits GSSG back into two GSH. It does this by transferring hydrogen from NADPH and carries FAD, which is derived from vitamin B2. Source 4
8. Foreign compound → GSH conjugate GST · GSH Glutathione S-transferases (GST) link glutathione to the foreign compound. The product is more water-soluble than the starting substance and is exported from the cell. Source 5
9. GSH conjugate → Mercapturic acid Peptidases, NAT · acetyl-CoA Peptidases trim the conjugate down to the cysteine residue; an acetyl group is added. As mercapturic acid, the substance leaves the body in the urine. Source 5, 4

Cofactors in this pathway

• Cysteine — Building block of glutathione and the part that runs short first Source 1, 2
• Glutamate — Building block of glutathione; GCL joins it to cysteine Source 1In the ORY catalogue as a laboratory value: Glutamat
• Glycine — Building block of glutathione; glutathione synthase adds it last Source 1In the ORY catalogue as a laboratory value: Glycin
• Vitamin B6 — Cofactor (PLP) of CBS and CSE on the way from homocysteine to cysteine Source 2In the ORY catalogue as a laboratory value: Vitamin B6
• Selenium — Present as selenocysteine in the active site of the glutathione peroxidases Source 3In the ORY catalogue as a laboratory value: Selen
• NADPH — Hydrogen donor of glutathione reductase, which turns GSSG back into two GSH Source 4
• Vitamin B2 (FAD) — Flavin cofactor of glutathione reductase Source 4
• Serine — Partner of homocysteine in the CBS reaction that leads to cystathionine Source 2In the ORY catalogue as a laboratory value: Serin

What acts on this pathway

• Paracetamol — When paracetamol is broken down in the liver, the reactive intermediate NAPQI is formed. Glutathione S-transferases bind it to glutathione for excretion; glutathione is used up in the process. Source 6

Sources

1. Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013 · PubMed 22995213
2. Sbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway. Br J Pharmacol 2019 · PubMed 30007014
3. Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta 2013 · PubMed 23201771
4. Deponte M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 2013 · PubMed 23036594
5. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005 · PubMed 15822171
6. Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014 · PubMed 24080471

Related pathways

• Methylation: methionine and homocysteine — homocysteine
• 8-OHdG — hydrogen peroxide
• Selenium — hydrogen peroxide
• Vitamin B6 — homocysteine
• Mycotoxins — mercapturic acid

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert approval pending
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