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  • Title: Iodothyronine metabolism in rat liver homogenates.
    Author: Kaplan MM, Utiger RD.
    Journal: J Clin Invest; 1978 Feb; 61(2):459-71. PubMed ID: 340472.
    Abstract:
    To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) and degradation of 3,3',5'-triiodothyronine (rT(3)) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T(4) to T(3), the K(m) of T(4) was 7.7 muM, and the V(max) was 0.13 pmol T(3)/min per mg protein. For rT(3) degradation, the K(m) of rT(3) was 7.5 nM, and the V(max) was 0.36 pmol rT(3)/min per mg protein. Production of rT(3) or degradation of T(4) or T(3) was not detected under the conditions employed. rT(3) was a potent competitive inhibitor of T(4) to T(3) conversion with a K(i) of 4.5 nM; 3,3'-diiodothyronine was a less potent inhibitor of this reaction. T(4) was a competitive inhibitor of rT(3) degradation with a K(i) of 10.2 muM. 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 alpha-methylparatyrosine, Fe(+2), Fe(+3), reduced glutathione, beta-hydroxybutyrate, or oleic acid. Fasting resulted in inhibition of T(4) to T(3) conversion and of rT(3) degradation by rat liver homogenates which was reversible after refeeding. Serum T(4), T(3), and thyrotropin concentrations fell during fasting, with no decrease in serum protein binding as assessed by a T(3)-charcoal uptake. There was no consistent change in serum rT(3) concentrations. Dexamethasone had no effect in vitro. In vivo dexamethasone administration resulted in elevated serum rT(3) concentrations after 1 day, and after 5 days, in inhibition of T(4) to T(3) conversion and rT(3) degradation without altering serum T(4), T(3), or thyrotropin concentrations. Endotoxin treatment had no effect of iodothyronine metabolism in liver homogenates. In kidney homogenates the reaction rates and response to propylthiouracil in vitro were similar to those in liver. No significant T(4) to T(3) conversion or rT(3) production or degradation could be detected in other tissues. These data suggest that one iodothyronine 5'-deiodinase is responsible for both T(4) to T(3) conversion and rT(3) degradation in liver and, perhaps, in kidney. Alterations in serum T(3) and rT(3) concentrations induced by drugs and disease states may result from decreases in both T(3) production and rT(3) degradation consequent to inhibition of a single reaction in the pathways of iodothyronine metabolism.
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