To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and degradation of 3,3′,5′-triiodothyronine (rT3) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T4 to T3, the Km of T4 was 7.7 μM, and the Vmax was 0.13 pmol T3/min per mg protein. For rT3 degradation, the Km of rT3 was 7.5 nM, and the Vmax was 0.36 pmol rT3/min per mg protein. Production of rT3 or degradation of T4 or T3 was not detected under the conditions employed. rT3 was a potent competitive inhibitor of T4 to T3 conversion with a Ki of 4.5 nM; 3,3′-diiodothyronine was a less potent inhibitor of this reaction. T4 was a competitive inhibitor of rT3 degradation with a Ki of 10.2 μM. Agents which inhibited both reactions included propylthiouracil, which appeared to be an allosteric inhibitor, 2,4-dinitrophenol, and iopanoic acid. Sodium diatrizoate had a weak inhibitory effect. No inhibition was found with α-methylparatyrosine, Fe+2, Fe+3, reduced glutathione, β-hydroxybutyrate, or oleic acid.
