Iodothyronine deiodinase 1 and Iodothyronine deiodinase 2 (DIO1 and DIO2)

Type 1 and type 2 iodothyronine deiodinases (DIO1, DIO2) are membrane-bound selenoenzymes responsible for activating thyroid hormone by outer ring deiodination of thyroxine (T4) to produce triiodothyronine (T3), the major active form of thyroid hormone[1][3][4]. DIO1 is mainly expressed in the liver, kidney, thyroid, and pituitary, playing a key role in the production of circulating T3, especially during hyperthyroid states[3][7]. DIO2 is primarily responsible for local (intracellular) T3 production in tissues such as the brain, pituitary, brown adipose tissue, and skeletal muscle; its expression is upregulated in hypothyroid conditions to maintain cellular T3 concentrations[3][7]. Both enzymes rely on the rare amino acid selenocysteine for catalytic activity[1][4][7]. Dysfunction, genetic defects, or pharmacological inhibition of these enzymes may contribute to endocrine diseases, including hypothyroidism, and have roles in cancer and potentially other conditions, such as neurodevelopmental or neurodegenerative disorders[2][3][4][7][8].

Other names

Type 1 deiodinaseType 2 deiodinaseD1 (for type 1)D2 (for type 2)Thyroxine 5'-deiodinase 1 (rare for DIO1)Thyroxine 5'-deiodinase 2 (rare for DIO2)

Inhibition of enzymatic deiodination (outer ring deiodination of T4 to T3)[4]; Modulation of T3 production.