IThyroid Peroxidase-Catalyzed Delabeling of131I-Diiodotyrosine and131I-Thyroxine1

The reaction between H2O2, thyroid peroxidase and the labeled iodoamino acids 131IDIT and 131I-T4 was studied in a reaction mixture that permitted simultaneous measurement of delabeling and labeling of the iodoamino acids. Under the incubation conditions used here the major reaction between 131I-DIT and the peroxidase system was an exchange between the iodine atoms of DIT and inorganic iodide. The exchange reaction was highly dependent on the initial iodide concentration and was inhibited by MMI and PTU, but not by dinitrotyrosine. These findings, coupled with the observation that thyroid peroxidase does not catalyze a net deiodination of DIT, make it unlikely that thisenzyme functions as a physiological deiodinase in the thyroid. 131I-T4 showed the following differences compared to 131I-DIT when incubated under similar conditions with the thyroid peroxidase system: 1) there was a marked net decrease in stable T4 concentration; 2) there was much less labeling of T4 by 125I-iodide present in the reaction mixture; 3) a higher percentage of the initial 131I appeared in products other than iodide; and 4) the reaction was much less dependent on iodide concentration. From these observations we conclude that degradation of T4molecules played a greater role than exchange in the reaction between T4 and thyroid peroxidase. 131I-T3 was not observed as a consistent product of the reaction, suggesting that peripheral conversion of T4 to T3 does not involve a peroxidase. The possibility was examined that exchange between 131I- and iodotyrosine might explain the previous observation reported from this laboratory of an apparent inhibitory effect of excess iodide on thyroid peroxidase-catalyzed iodination of thyroglobulin. Experiments employing stable iodine analysis confirmed this conclusion, thus ruling out an artifact of exchange. (Endocrinology95:1166, 1974)