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
Multienzymatic hybrid bio-heterojunction for synergistic microenvironment reprogramming and selenoprotein-activated mitochondrial bioenergetics in diabetic osseointegration.
Zhang M, Lu M, Chen Y, Ming M, Luo B, Wu Y. · 2026-09-16
open access unreviewed -
2
Antifungal mechanisms of volatile organic compounds and lactic acid produced by Lactiplantibacillus pentosus and their biocontrol application in fresh corn against Fusarium graminearum.
Zhang Y, Li J, Qiu Y, Zhao Y, Wang H, Cai C, Zhu J. · 2026-08-18
unreviewed -
3
A universal consuming endogenous H<sub>2</sub>S strategy using bismuth-metal-organic nanocapsule networks for overcoming osteosarcoma cisplatin resistance.
Lin Y, Yuan K, Liu Y, Du Y, Chang H, Hou L, Liang Y, Huang K, Yang S, Tang T. · 2026-08-18
open access unreviewed -
4
Key molecular networks underlying retinol's biphasic effects on cell proliferation through multi-omics integrative analysis using genome-scale metabolic modeling.
He P, Xiang G, Yan Y, Zhong J, Liang Y, Shu P, Lu H. · 2026-06-19
open access unreviewed -
5
CPT-TCPP polymeric nanoplatform for sonodynamic-chemotherapy synergistic tumor therapy through ferroptosis-apoptosis dual cell death reprogramming.
Wang L, Zhang Z, Liu Q, Zhang H, Peng J, Wang D. · 2026-09-22
open access unreviewed -
6
Ferroptosis in major depressive disorder: Molecular mechanisms, cellular vulnerability, and therapeutic opportunities.
Kong D, Duan R, Wang X, Wang X, Zhao J. · 2026-09-18
open access unreviewed -
7
Low-dose l-carnitine supplementation attenuates hepatic lipid accumulation in chow-fed mice: Insights from integrated multi-omics analysis.
Zhang Z, Ding B, Zhang L, Zhang L, Huang Y. · 2026-09-10
open access unreviewed -
8
Responses of arbuscular mycorrhizal wheat to salinity: from symbiotic signaling to stress adaptation.
Zamir H, Rauf F, Jamali ZH, Khan S, Zulfiqar U, Alotaibi MS, Muminov M, Abdusamatov S, Gururani MA, Korai SK. · 2026-09-23
open access unreviewed -
9
Metabolic regulation of oocyte maturation and early embryo development in mammals.
Rong S, Fu Y, Li Y, Jiang YC, Chen L, Zhao Y, Zhu W, Mu L. · 2026-08-06
open access unreviewed -
10
From molecules to medicine: the gut‒heart axis comes of age.
Pretorius T, Marques FZ. · 2026-09-19
open access unreviewed
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