Glutathione-Related Enzymes and Proteins: A Review Original paper

What was reviewed?

This review examined glutathione-related enzymes inflammation by detailing how the glutathione system regulates redox balance, antioxidant defense, detoxification, and cellular signaling under physiological and inflammatory conditions. The authors described glutathione synthesis, distribution, and cycling between reduced and oxidized forms, then explained how this redox system supports enzymatic networks that control peroxide removal, electrophile detoxification, and thiol-based regulation of proteins. The review centered on glutathione peroxidases, glutathione reductase, glutaredoxins, peroxiredoxins, glutathione-S-transferases, and glyoxalase enzymes, with emphasis on how these enzymes preserve cellular stability during oxidative stress and inflammation.

Who was reviewed?

The paper synthesized findings from experimental models and human studies across multiple tissues rather than a defined clinical cohort. It reviewed evidence from organs with high metabolic activity and oxidative exposure, including liver, kidney, intestine, lung, brain, and vascular tissue. The authors discussed disease contexts such as chronic inflammation, viral infection, cancer, diabetes, cystic fibrosis, neurodegeneration, and cardiovascular disease, where altered glutathione metabolism and enzyme dysfunction contribute to tissue injury. These systems reflect clinical settings in which redox imbalance and inflammatory stress drive disease progression.

Most important findings

The review showed that glutathione-related enzymes act as an integrated defense network that limits oxidative damage and regulates inflammatory signaling. The authors highlighted compartment-specific control, where cytosolic glutathione supports redox signaling, mitochondrial glutathione protects oxidative phosphorylation, and endoplasmic reticulum glutathione balances protein folding and disulfide bond formation. Glutathione peroxidases emerged as primary peroxide-scavenging enzymes that reduce hydrogen peroxide and lipid peroxides, thereby preventing membrane damage and inflammatory amplification. The review emphasized glutathione peroxidase 2 in epithelial tissues as a key enzyme that responds to oxidative challenge. γ-Glutamyl transpeptidase appeared as a central regulator of extracellular glutathione breakdown and amino acid recycling, which sustains intracellular glutathione synthesis during stress.

Glutaredoxins controlled reversible protein glutathionylation, protecting cysteine residues from irreversible oxidation and modulating signaling proteins involved in inflammation and cytoskeletal dynamics. Peroxiredoxins function as both peroxide detoxifiers and redox sensors that transmit oxidative signals at low peroxide levels. Glutathione-S-transferases extended glutathione activity to detoxification of xenobiotics and endogenous electrophiles, influencing drug metabolism and inflammatory burden. The glyoxalase system links glutathione to the detoxification of reactive carbonyl species generated during high glycolytic flux, which becomes prominent in inflamed and metabolically stressed tissues. Together, these findings positioned glutathione enzymes as regulators of both antioxidant defense and controlled redox signaling rather than simple scavengers.

Key implications

For clinicians, this review clarifies how glutathione-related enzymes define cellular resilience during oxidative and inflammatory stress. Reduced glutathione availability or impaired enzyme activity can shift cells toward persistent oxidative damage, exaggerated inflammatory signaling, and tissue dysfunction. The paper supports clinical interpretation of redox biomarkers and highlights enzyme-specific targets that may influence disease severity or treatment response. It also cautions that boosting glutathione alone may not restore balance without intact enzyme systems and proper compartmental control. The review, therefore, provides a mechanistic framework for understanding inflammation-driven diseases through redox biology rather than offering direct therapeutic prescriptions.