Inhibition of Thyroidal Iodotyrosine Deiodination byTyrosine Analogues

Abstract

The effect of several tyrosine derivatives on deiodination of 3,5-diiodo-L-tyrosine (DIT) was examined in vitro and in vivo. In TPNH-supple-mented sheep thyroid homogenates, the most effective inhibitors of deiodination, in order of increasing potency, were 3,5-dibromo-L-tyrosine (DBT), 3,5-dinitro-L-tyrosine (DNT) and 3-nitro-L-tyrosine (MNT); kinetic studies suggested purely competitive inhibition. Compounds with weak or no inhibitory activity included tyrosine itself, its 3-methyl-, 3-isopropyl-, 3-n-propyl- and 3-amino-derivatives, and 3,4-dihydroxy-L-phenyl-alanine. DBT, DNT and MNT also inhibited deiodination of DIT by sheep thyroid slices. In rats, administration of DBT, DNT or MNT with I131-DIT inhibited deiodination, and led to the appearance of an unknown DIT metabolite in blood and urine-Administration of the most potent in vitro inhibitor, MNT, to rats prelabeled with radio I was followed by the urinary excretion of large amouuts of a similar unknown organic I compound, together with small amounts of DIT and of monoiodotyrosine. MNT can inhibit the deiodination of endogenously formed iodotyrosines.