Glutathione Metabolism (gamma-Glutamyl Cycle)
- Compartment
- Cytosol
- Main tissue
- All cells; highest in liver and RBC
- Rate-limiting
- gamma-Glutamylcysteine synthetase (GCL)
- Steps
- 5
Reaction steps
In source order, 5 total
-
1
L-Glutamate + L-cysteine + ATP -> gamma-glutamylcysteine + ADP + Pi
› Notes
Rate-limiting step; feedback-inhibited by GSH. Cysteine availability is usually the limiting substrate.
-
2
gamma-Glutamylcysteine + glycine + ATP -> glutathione (GSH) + ADP + Pi
› Notes
Deficiency causes 5-oxoprolinuria (pyroglutamic aciduria) with haemolytic anaemia.
-
3
2 GSH + H2O2 -> GSSG + 2 H2O
› Notes
Selenocysteine enzyme; the principal peroxide defence of the erythrocyte.
-
4
GSSG + NADPH + H+ -> 2 GSH + NADP+
› Notes
Links antioxidant defence to the pentose phosphate pathway; this is why G6PD deficiency causes oxidative haemolysis. Riboflavin (FAD) dependent.
-
5
Xenobiotic/electrophile + GSH -> GS-conjugate -> mercapturic acid
› Notes
Phase II conjugation; depletion of GSH by NAPQI underlies paracetamol (acetaminophen) hepatotoxicity, treated with N-acetylcysteine.
Showing all 5 steps.
Recent literature
Live Europe PMC search
Europe PMC · fetched just now · sorted by publication date
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1
Metabolic disruption associated with e-cigarette vaping and secondhand exposure: Urinary metabolomics evidence from a Thai population.
Tajai P, Sawatdikun S, Srisopa T, Konguthaithip G, Parinyarux P, Ditsawanon P, Charoensook P. · 2026-07-11
unreviewed -
2
Paeoniae decoction attenuates chronic colitis-associated intestinal fibrosis by suppressing TGF-β/Smad-mediated epithelial-mesenchymal transition and remodeling the metabolic microenvironment.
Zhao M, Yi Q, Liang J, Li C, Ke X, Zhao Y, Shi Y, Deng S, Wang Q, Luo X, Zhou L. · 2026-06-24
unreviewed -
3
Effects of dinotefuran and its metabolites on the early life stage development of medaka (<i>Oryzias latipes</i>): <i>In vivo</i> and <i>in silico</i> studies.
Hirano M, Inoue D, Uchida M, Takahashi K, Kato K, Okobira T, Ishibashi H, Arizono K, Tominaga N. · 2026-06-12
open access unreviewed -
4
Comparative transcriptomic and metabolomic profiling of forest tea and terrace tea in Sandu, Guizhou, China.
Wei D, Wu H, Yang M, Sarathchandra C, Geng Y. · 2026-06-02
open access unreviewed -
5
Synergistic application of taurine and spermidine enhances wheat tolerance to neodymium stress through redox homeostasis, metabolic adjustment, and nutrient regulation.
Iqbal R, Mehmood H, Majeed A, Murtaza G, Rebouh NY, Alotaibi MS, Alotaibi SS, Ullah S, Huseynova A, Ali S. · 2026-06-15
open access unreviewed -
6
Significance of GSH and H<sub>2</sub>S regulation for cancer: an intricate interplay between diet, microbiota, metabolic reprogramming, and immune health.
Majumder A, Majumder S, Bano S, Sen K, Nayak KB. · 2026-06-11
open access unreviewed -
7
Uric acid alleviates the inflammatory response in LPS-induced BV2 cells and MPTP-induced PD mice by resisting ferroptosis through the Nrf2 signalling pathway.
Zhou D, Xiong T, Yang B, Liu F, Mo X, Chen T, Lu P, Liang X, Li L, Qin Y, Lu D, Huang F, Yang X. · 2026-06-04
open access unreviewed -
8
Exogenous pipecolic acid ameliorates lead-induced phytotoxicity in chili (<i>Capsicum annuum</i> L.) by enhancing antioxidant capacity and physiological homeostasis.
Iqbal R, Mehmood H, Majeed A, Murtaza G, Huseynova A, Ullah S, Ditta A, Aldahmash B, Rady A. · 2026-06-01
cited 1× open access unreviewed -
9
The RNAi machinery regulates lovastatin biosynthesis via microRNA-like RNAs in industrial <i>Aspergillus terreus</i>.
Gu M, Feng D, Liu Y, Zhang W, Zhou Y, Zhang X, Du S, Huang X, Lu X. · 2026-05-11
open access unreviewed -
10
Sauchinone attenuates UVB-induced photoaging by suppressing oxidative stress and ferroptosis through activation of the Keap1-Nrf2 pathway in dermal fibroblasts.
Zhang X, Wang J, Zhou Y, Shen C, Yuan M, Li Q, Li W. · 2026-05-21
open access unreviewed
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