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

Abstract

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 rT 3 and 3′,5′-T 2 by rat liver microsomes. At pH 7.2 the K m values of the 5′-deiodination of rT 3 and 3′,5′-T 2 were 0.103 and 0.77 μM, respectively. 3′,5′-T 2 and rT 3 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 rT 3 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 T 4-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 rT 3 and 3′,5′-T 2, a positive correlation between these values was found ( r = 0.97). It was concluded that rT 3 (to 3,3′-T 2) and 3′,5′-T 2 (to 3′-T 1) 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.