Sequential deiodination of thyroxine in rat liver homogenate.
Rat liver homogenate was incubated at 37 degrees C with thyroxine, 3,3',5-tri-iodothyronine, 3,3',5'-tri-iodothyronine or 3,3'-di-iodothyronine. The degradation or accumulation of these compounds was measured by specific radioimmunoassays. (1) Production of 3,3',5-tri-iodothyronine from thyroxine was highest at pH 6.0--6.5 and was markedly stimulated by the addition of dithiothreitol and effectively inhibited in the presence of 6-propyl-2-thiouracil. (2) Accumulation of 3,3',5'-tri-iodothyronine on incubation of thyroxine with homogenate was only observed above pH 8.5. Otherwise the product was converted into 3,3'-di-iodothyronine too rapidly to allow its measurement. By measuring 3,3'-di-iodothyronine it was deduced that 5-deiodination of thyroxine was most effective at approx. pH 8.0. Dithiothreitol powerfully stimulated this reaction and 6-propyl-2-thiouracil strongly inhibited. (3) Monodeiodination of the tyrosine ring of 3,3',5-tri-iodothyronine was the slowest reaction, was optimal at pH 8.0 and was less affected by dithiothreitol and 6-propyl-2-thiouracil than the above reactions. (4) 5'-Deiodination of 3,3',5'-tri-iodothyronine was extremely rapid, with a pH optimum probably at about 6.5. Owing to the high reaction rate under the conditions used it was not possible to assess the effects of dithiothreitol and 6-propyl-2-thiouracil.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004104:Diiodothyronines / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D004104:Diiodothyronines; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D011441:Propylthiouracil; D004492:Edetic Acid; D013974:Thyroxine; D004229:Dithiothreitol