The mammalian thioredoxin reductases （TrxRs） are a family of seleno-cysteine containing pyridine nucleotide-disulfide oxido-reductases. All the mammalian TrxRs are homologous to glutathione reductase with respect to primary structure including the conserved redox catalytic site （-Cys-Val-Asn-Val-Gly-Cys-） but distinctively with a C-terminal extension containing a catalytically active penultimate seleno-cysteine （SeCys） residue in the conserved sequence（-Gly-Cys-SeCys-Gly）. TrxR is homodimeric protein in which each monomer includes an FAD prosthetic group，a NADPH binding site and a redox catalytic site. Electrons are transferred from NADPH via FAD and the active-site disulfide to C-terminal SeCys-containing redox center，which then reduces the substrate like thioredoxin. The members of TrxR family are 55 – 58 kDa in molecular size and composed of three isoforms including cytosolic TrxR1，mitochondrial TrxR2，and TrxR3，known as Trx and GSSG reductase （TGR）. TrxR plays a key role in protection of cells against oxidative stress and redox-regulatory mechanism of transcription factors and various biological phenomena. TrxR1 plays a central role as a glucosyl donor in cellular metabolic pathways.
