Type II iodothyronine deiodinase (DIO2) (DIO2)

Type II iodothyronine deiodinase (DIO2) is a selenium-containing enzyme that plays a pivotal role in the activation of thyroid hormones within target tissues [UniProt, NIH]. It primarily catalyzes the conversion of the prohormone thyroxine (T4) into the biologically active 3,5,3'-triiodothyronine (T3) by removing an iodine atom from the outer phenolic ring [Wikipedia, NIH]. DIO2 is expressed in critical sites such as the brain, pituitary gland, skeletal muscle, and brown adipose tissue, where it ensures a steady supply of intracellular T3 regardless of fluctuating serum levels [NIH, MDPI]. This localized production is essential for brain development, metabolic rate regulation, and adaptive thermogenesis [NIH]. Furthermore, DIO2 in the hypothalamus and pituitary is a key component of the negative feedback loop that regulates the hypothalamic-pituitary-thyroid (HPT) axis [NIH]. Dysregulation or genetic variants of DIO2, such as the Thr92Ala polymorphism, have been linked to metabolic syndromes, neurodegenerative diseases, and altered responses to thyroid hormone replacement therapy [NIH]. Pharmacological agents like iopanoic acid and amiodarone can inhibit DIO2 activity, potentially leading to localized thyroid hormone deficiencies and systemic metabolic changes [NIH, Endocrine Abstracts].

Other names

Type 2 iodothyronine 5'-deiodinaseDeiodinase type IID25DIIDIOIIIodothyronine 5'-deiodinase type 2Selenoprotein YTXDI2

Inhibition of outer-ring deiodination (ORD) of thyroxine (T4) to triiodothyronine (T3), thereby reducing the intracellular availability of the active thyroid hormone.