The three iodothyronine deiodinases catalyze the initiation (D1, D2) and termination (D3) of thyroid hormone effects in vertebrates. A recently conceived 3-dimensional model predicts that these enzymes share a similar structural organization and belong to the thioredoxin (TRX) fold superfamily. Their active center is a selenocysteine-containing pocket defined by the b1-a1-b2 motifs of the TRX fold and a domain that shares strong similarities with the active site of iduronidase, a member of the clan GH-A fold of glycoside hydrolases. While […]

Thyroid hormones play an important role on growth, development and metabolism of all vertebrates. Serum concentration of thyroid hormones are controlled by TRH, somatostatin and TSH which determine the rate of hormone biosynthesis and release, as well as by deiodinases (mainly type I), enzymes which generate in peripheral tissues, approximately 75% of the T3 present in serum, from circulating T4; type II deiodinases, on the other hand, are supposed to generate T3 for the tissues in which they are expressed. […]

Thyroxine (T4) is the main product of thyroid secretion, a pro-hormone that must be activated by deiodination to T3 in order to initiate thyroid hormone action. This deiodination reaction occurs in the phenolic-ring (outer-ring deiodination, ORD) of the T4 molecule and is catalyzed by two selenocysteine-containing deiodinases, i.e. D1 and D2. As a counter point to the activation pathway, both T4 and T3 can be irreversibly inactivated by deiodination of the thyrosyl-ring (inner-ring deiodination, IRD), a reaction catalyzed by D3, […]