Monodeiodination of 3,5,3′-Triiodothyronine and 3,3′,5′- Triiodothyronine to 3,3′-Diiodothyroninein Vitro*

Abstract

To study conversion of 3,5,3''-triiodothyroinine (T3) and 3,3'',5''-triiodothyronine (rT3) to 3,3''-diiodothyronine (T2) in vitro, T3 or rT3 was incubated at pH 7.35 with homogenates of several rat tissues (liver, kidney, muscle, heart, lung, spleen, intestines and brain) for 15 min at 37.degree. C. The T2 generated during incubation was measured in an ethanol extract of the incubation mixture by a specific RIA [radioimmunoassay] of T2; T4, T3, and rT3 cross-reacted in the T2 RIA only to an extent of 0.006, 0.2 and 0.04%, respectively. T2 was produced regularly when T3 or rT3 was incubated with liver or kidney homogenates; other tissues generated little or no T2 under similar conditions. Studies with liver homogenates revealed tha production of T2 from both T3 and rT3 was influenced significantly by tissue and substrate concentrations, temperature, pH and duration of incubation. T3- as well as rT3-monodeiodinating activities were unaffected by large doses (.gtoreq. 3 .mu.mol) of NaI diiodotyrosine and methimazole, but were inhibited in a dose-dependent manner by propylthiouracil, iodoacetic acid and dinitrophenol. The apparent Km for conversion of T3 to T2 approximated 6.0 .mu.M and that for conversion of rT3 to T2'' 65 nmol. Propylthiouracil and iodoacetic acid inhibited conversion of both T3 and rT3 to T2 in an uncompetitive and a non-competitive manner respectively. Monodeiodination of T3 and rT3 to T2 is apparently enzymic in nature and liver and kidney may be the major sites of metabolic transformations of T3 and rT3 to T2.