Iodothyronine deiodinase type 1 (DIO1)

Iodothyronine deiodinase type 1 (DIO1) is a selenium-containing enzyme primarily located in the liver, kidney, and thyroid gland [3, 11]. It plays a central role in thyroid hormone homeostasis by catalyzing the deiodination of the prohormone thyroxine (T4) into the biologically active triiodothyronine (T3), as well as the inactivation of T4 into reverse T3 (rT3) [1, 4]. DIO1 is a major contributor to the pool of circulating T3 in the blood, making it essential for regulating systemic metabolism, growth, and development [3, 5]. In disease states, overactivity of DIO1 is a hallmark of hyperthyroidism and thyroid storm, leading to excessive T3 production [2, 12]. Conversely, its expression is often downregulated in nonthyroidal illness syndrome and various cancers, such as thyroid and renal cell carcinomas [2, 15]. DIO1 is a primary pharmacological target for the antithyroid drug propylthiouracil (PTU), which inhibits the enzyme to rapidly reduce peripheral T3 levels [12, 16]. Other substances, including amiodarone and certain environmental endocrine disruptors like bisphenol A, also interact with DIO1, highlighting its importance in both clinical management and toxicological assessment [12, 15].

Other names

Type I iodothyronine deiodinase5'-deiodinase5DITHMA2TXDI1

Inhibition of the enzyme's catalytic activity by competing with endogenous thiols for the reduction of the selenocysteine-iodine complex, thereby preventing the conversion of T4 to T3 [16].