Evidence for a single enzyme in rat liver catalysing the deiodination of the tyrosyl and the phenolic ring of iodothyronines

Abstract

The enzymic 5′-deiodination of 3′,5′-di-iodothyronine and 5-deiodination of 3,3′,5-tri-iodothyronine by rat liver microsomal fractions were found to be characterized by apparent Km values of 0.77 and 17.4 microM respectively, 3′,5′-Di-iodothyronine was a competitive inhibitor of 3,3′,5-tri-iodothyronine 5-deiodination (Ki 0.65 microM) and 3,3′,5-tri-iodothyronine was a competitive inhibitor of 3′,5′-di-iodothyronine 5′-deiodination (Ki 19.6 microM). In addition, several radiographic contrast agents and iodothyronine analogues inhibited both reactions competitively and with equal potencies (r = 0.999). These results strongly suggest the existence of a single hepatic deiodinase acting on both the tyrosyl and phenolic ring of iodothyronines.

Thyroxine Inner Ring Monodeiodinating Activity in Fetal Tissues of the Rat

“…We do not know of gestation in the intestine while they both decrease in skeletal muscle (Tables 1 and 2). The similarly in maturational pattern of 5'-MA and 5-MA is consistent with the notion that they may be a function of the same enzyme in several tissues as suggested in the liver (37)(38)(39). However, the magnitude of changes in 5'-MA and 5-MA differed suggesting that different factors regulate the two activities or that the enzymes involved are distinct.…”

Decreased transport of thyroxine (T4), 3,3′‐5‐triiodothyronine (T3) and 3,3′,5′‐triiodothyronine (rT3) into rat hepatocytes in primary culture due to a decrease of cellular ATP content and various drugs

“…Because of the structural similarities between these compounds and thyroid hormone, their effect can be explained by competitive inhibition of uptake, as has been shown for T4 conversion [26].…”

“…Many compounds [24] (e.g., X-ray contrast agents, propranolol, amiodarone) can induce a low Ts syndrome, which has been explained by inhibition of the activity of 5'-deiodinase. However, 50% inhibition of this activity in isolated hepatocytes [25] or homogenates [26] has been achieved with -500 PM D,L-propranolol, -3 orders of magnitude higher than in vivo plasma levels of subjects given the usual therapeutic dosage [27]. Furthermore, a membrane-stabilizing effect seems to be achieved with concentrations of propranolol, which are -1 order of magnitude higher than the usual therapeutic plasma level [27].…”

Iodothyronine Deiodinases: Key Enzymes Behind the Action of Thyroid Hormone

“…Of the three deiodinases, D1 is a multifunctional enzyme that can catalyze both ORD and IRD, with the values of MichaelisMenten constant (Km) for ORD and IRD both within a micromolar range (Fekkes et al, 1982). The Km value corresponds to the substrate concentration when the velocity of the enzyme reaction is half-maximum; Higher the Km value, the enzyme is roughly considered less efficient in catalyzing the substrate (Johnson, 2013).…”