Iodothyronine deiodinase type II (DIO2)

Iodothyronine deiodinase type II (DIO2) is a critical selenoprotein enzyme that facilitates the intracellular activation of thyroid hormones. It primarily converts the prohormone thyroxine (T4) into the biologically active form, triiodothyronine (T3), through outer-ring deiodination. Unlike the type I deiodinase, DIO2 is essential for maintaining local T3 concentrations in specific tissues such as the brain, pituitary gland, and brown adipose tissue, and it is largely resistant to inhibition by propylthiouracil. DIO2 plays a pivotal role in adaptive thermogenesis, neurodevelopment, and the negative feedback regulation of the hypothalamic-pituitary-thyroid axis. Genetic polymorphisms in the DIO2 gene, most notably the Thr92Ala variant, have been associated with insulin resistance, neurodegenerative diseases, and impaired psychological well-being in patients receiving standard T4 replacement therapy. Pharmacological agents such as iopanoic acid and amiodarone act as inhibitors of DIO2, potentially leading to altered thyroid homeostasis, while other drugs like pioglitazone can upregulate its expression to influence metabolic pathways.

Other names

Type II iodothyronine deiodinaseType 2 deiodinaseD2DIOII5DIIThyroxine 5'-deiodinase type IISELENOYSelYTXDI2

Catalyzes the activation of the prohormone thyroxine (T4) into the biologically active hormone triiodothyronine (T3) by removing an iodine atom from the outer (phenolic) ring (5'-deiodination).