Thioredoxin reductase and related oxidoreductases (TrxR)

Thioredoxin reductase (TrxR) and related oxidoreductases, such as glutathione reductase, are a family of flavoenzymes that play a critical role in maintaining cellular redox homeostasis. In mammals, TrxRs are unique selenoproteins that utilize a C-terminal selenocysteine residue to catalyze the NADPH-dependent reduction of thioredoxin and other substrates. This system is essential for various cellular processes, including DNA synthesis via ribonucleotide reductase, antioxidant defense, and the regulation of redox-sensitive signaling pathways and transcription factors. Due to their frequent overexpression in cancer cells to counteract high levels of reactive oxygen species (ROS), these enzymes have emerged as promising therapeutic targets. Inhibition of TrxR, particularly by gold-containing compounds like auranofin or electrophilic drugs like cisplatin, disrupts the redox balance, leading to lethal oxidative stress and apoptosis in malignant cells. Beyond oncology, these enzymes are also investigated as targets for treating inflammatory, neurodegenerative, and infectious diseases.

Other names

Pyridine nucleotide-disulfide oxidoreductasesThioredoxin systemTrxR familySelenoprotein oxidoreductases

Inhibition of the enzyme's catalytic activity (often by targeting the C-terminal selenocysteine residue), leading to accumulation of oxidized thioredoxin, increased reactive oxygen species (ROS), and induction of apoptosis.