Antioxidant and detoxification enzymes

Antioxidant and detoxification enzymes are a collective group of proteins essential for maintaining cellular integrity against oxidative and chemical insults. This group includes primary antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), which neutralize reactive oxygen species (ROS), as well as Phase II detoxification enzymes such as glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase 1 (NQO1) [1, 2]. These enzymes are coordinately regulated by the transcription factor Nrf2 (Nuclear factor erythroid 2-related factor 2), which translocates to the nucleus under stress conditions to bind the Antioxidant Response Element (ARE) in the promoter regions of these genes [2]. Dysregulation of this system is implicated in a wide range of pathologies, including neurodegenerative diseases, chronic inflammation, and cancer, where oxidative damage drives disease progression [3]. Pharmacological modulation typically involves Nrf2 activators, such as dimethyl fumarate and omaveloxolone, which enhance the expression of these enzymes to provide cytoprotection [4, 5]. However, the therapeutic window must be carefully managed, as over-expression of these enzymes in cancer cells can lead to drug resistance and tumor survival [1].

Other names

Phase II detoxifying enzymesCytoprotective enzymesARE-regulated enzymesRedox-regulating enzymesAntioxidant response element-regulated enzymes

Induction of gene expression via the Nrf2/ARE signaling pathway [1, 2]; direct enzymatic neutralization of reactive oxygen species [3]; conjugation of electrophilic xenobiotics with glutathione [2].