Detoxification and antioxidant enzymes

Detoxification and antioxidant enzymes represent a broad functional class of proteins essential for maintaining cellular homeostasis and protecting against chemical and oxidative insults (Ighodaro & Akinloye, 2018, PMID: 29475244). This group includes Phase I and Phase II detoxification enzymes, such as Cytochrome P450s and Glutathione S-transferases, which metabolize xenobiotics, as well as primary antioxidant enzymes like Superoxide dismutase, Catalase, and Glutathione peroxidase, which neutralize reactive oxygen species (ROS) (Hayes & Pulford, 1995, PMID: 7730633). These enzymes are frequently co-regulated by the transcription factor Nrf2 (Nuclear factor erythroid 2-related factor 2) through the Antioxidant Response Element (ARE) in their promoter regions (Kansanen et al., 2013, PMID: 23238454). Pharmacological modulation of this system, typically through Nrf2 activators like Dimethyl fumarate or Bardoxolone methyl, aims to enhance the cell's innate defense mechanisms against oxidative stress and inflammation (Robledinos-Antón et al., 2019, PMID: 31159461). Consequently, these enzymes are key therapeutic targets in conditions characterized by high oxidative burden, including neurodegenerative diseases, chronic kidney disease, and cancer prevention.

Other names

Phase II detoxification enzymesAntioxidant response element (ARE) genesXenobiotic-metabolizing enzymes (XMEs)Redox enzymesAntioxidant defense system

Induction of gene expression via the Nrf2-Keap1-ARE signaling pathway; direct enzymatic neutralization of reactive oxygen species; conjugation of xenobiotics to facilitate excretion (Kansanen et al., 2013, PMID: 23238454).