Selenium-dependent antioxidant enzymes (Selenoproteins)

Selenium-dependent antioxidant enzymes, primarily known as selenoproteins, are a specialized group of proteins that incorporate the amino acid selenocysteine into their active sites to facilitate essential redox reactions. The most prominent members include the glutathione peroxidase (GPx) family, which neutralizes hydrogen peroxide and lipid hydroperoxides, and the thioredoxin reductase (TrxR) family, which maintains cellular thiol redox state and supports DNA synthesis (Labunskyy et al., 2014). These enzymes are vital for protecting cells from oxidative stress-induced damage and are involved in regulating thyroid hormone metabolism through the deiodinase family (Rayman, 2012). In clinical contexts, these enzymes are targeted either by providing selenium supplements to boost their activity or by using small molecule mimetics like ebselen to replicate their antioxidant function (Parnham & Sies, 2000). Conversely, inhibitors of thioredoxin reductase, such as auranofin, are investigated for their ability to disrupt the redox balance in cancer cells, leading to apoptosis (Arner, 2017). Because selenium has a narrow therapeutic window, pharmacological modulation of these enzymes must be carefully monitored to avoid toxicity known as selenosis.

Other names

SelenoproteinsSelenoenzymesSe-dependent enzymesSelenocysteine-containing enzymesGlutathione peroxidasesThioredoxin reductases

Drugs targeting these enzymes act as catalytic mimics of glutathione peroxidase to reduce oxidative stress, provide essential selenium substrates for de novo enzyme synthesis, or inhibit specific members like thioredoxin reductase to induce proteotoxic and oxidative stress in cancer cells.