Iodothyronine deiodinase (DIO)

Iodothyronine deiodinase is a family of selenocysteine-containing membrane enzymes crucial for thyroid hormone metabolism. These dimeric integral membrane proteins, sharing a thioredoxin (TRX) fold, catalyze the activation and inactivation of thyroid hormones through reductive iodide eliminations. There are three types: Type I (DIO1/D1), primarily found in liver and kidney, deiodinates both rings and acts as a major source of circulating T3, being sensitive to PTU. Type II (DIO2/D2), found in heart, skeletal muscle, CNS, fat, thyroid, and pituitary, deiodinates the outer ring, converting less active T4 to active T3 for local production. Type III (DIO3/D3), common in fetal tissue, placenta, and throughout the brain, deiodinates the inner ring, thereby inactivating T3 or T4. These enzymes regulate thyroid hormone activity at a cellular level, largely independent of circulating hormone concentrations, which is crucial for metabolic processes, development, and feedback control of the thyroid axis. Given their central role, iodothyronine deiodinases are considered therapeutic targets.

Other names

DeiodinasesDI

Inhibition of specific deiodinase types (e.g., PTU inhibits DIO1). Development of specific, deiodinase-targeting drugs aims to modulate their enzymatic activity to control thyroid hormone activation or inactivation.