The requirement for TH varies with

The requirement for TH varies with tissue, cell type and time. Control of TH entry into the cell through membrane transporters is apparently insufficient to provide the proper hormone supply. Further fine-tuning is achieved by the generation of active TH or by its inactivation at the site of action. D1 and D2 are 5′-iodothyronine deiodinases that catalyze TH activation by converting T4 to T3. D3, a 5-deiodinase, is the main TH inactivator through conversion of T4 to rT3 and T3 to T2.Deiodinases are selenoproteins containing the rare amino acid, selenocysteine (Sec), the presence of which in the active center is required for their enzymatic activity. The mechanism of selenoprotein synthesis is summarized below (see the section The SBP2 gene, its product, function, and mutations). Deiodinases are differentially expressed in tissues and are further regulated at the level of transcription, translation, and metabolism by alterations in the intracellular environment.10 D2 activity can change very rapidly as its half-life is more than 15-fold less that that of D1 and D3. D2 inactivation, mediated through ubiquitination, is accelerated by T4, a process reversible by deubiquitination (for details, see Chapter 1).