One enzyme for the 5′-deiodination of 3,3′,5′-triiodothyronine and 3′,5′-diiodothyronine in rat liver

Many studies suggest that one enzyme is involved in the phenolic ring deiodination of iodothyronines in rat liver and kidney and another one in the tyrosyl ring deiodination. This study describes some characteristics of the phenolic ring (5′-) deiodination of rT₃ and 3′,5′-T₂ by rat liver microsomes. At pH 7.2 the K_m values of the 5′-deiodination of rT₃ and 3′,5′-T₂ were 0.103 and 0.77 μM, respectively. 3′,5′-T₂ and rT₃ inhibited the respective 5′-deiodination reactions competitively, the K_i values being 1.05 and 0.134 μM, respectively. Several radiographic contrast agents markedly inhibit the 5′-monodeiodination of rT₃ and 3′,5′T-₂, the type of inhibition being competitive. Of these compounds iopanoic acid, ipodic acid and iophenoxic acid are the most potent inhibitors with K_i values of approximately 2 μM for both reactions. The non-iodine containing compound 8-anilino-1-naphthalene sulphonic acid (ANS) appeared to be a very strong competitive inhibitor of both 5′-deiodinations (K_i 4.3–4.7 μM), whereas salicylic acid, which as ANS inhibits the binding of iodothyronines to T₄-binding globulin, inhibited these reactions to a much lesser extent (K_i 300–500 μM). On the other hand, diiodosalicylic acid was a very strong inhibitor. The β-adrenergic blocker d,l-propranolol was a weak noncompetitive inhibitor of both 5′-deiodinations (K_i 0.4–0.7 mM). These reactions were also inhibited by various 2,6-diiodophenol derivatives, triiodophenol being the strongest and diiodotyrosine the weakest inhibitor tested. Comparing the K_i values of various inhibitors for the 5′-deiodination of rT₃ and 3′,5′-T₂, a positive correlation between these values was found (r = 0.97). It was concluded that rT₃ (to 3,3′-T₂) and 3′,5′-T₂ (to 3′-T₁) monodeiodinating activities are very similar to each other and that there may just be one monodeiodinase catalyzing the 5′-deiodination of iodothyronines in rat liver.