THE METABOLISM OF I131-LABELED DIIODOTYROSINE

Abstract

Diiodotyrosineexists in the thyroid gland primarily as a component of protein thyroglobulin.Only about 1 to 2 per cent is present as the free amino acid (1).Evidence was presented in a previous communication to show that bound diiodotyrosine, and not the free amino acid, is the precursor of thyroxine in the thyroid gland (1).Roche and his coworkers have suggested that free mono-and diiodotyrosine are produced in the thyroid gland along with free thyroxine by proteolysis of thyroglobulin (2).The former two amino acids are not released into the circulation, according to these workers, because they are rapidly deiodinated in the thyroid gland itself, a fate not shared by thyroxine.Roche and his group have emphasized deiodination as the major metabolic fate of free (or added) diiodotyrosine, not only in the thyroid gland but in extrathyroidal tissues as well.On the other hand, shortly after the discovery of diiodotyrosine in the thyroid gland, Foster and Gutman (3) fed extremely large amounts of this amino acid to rabbits, and isolated from their urine a compound which was identified as 3,5-diiodo-4-hydroxyphenyllactic acid.This finding suggests that deamination may be an important step in the metabolism of diiodotyrosine in the intact animal.A similar observation was recently reported by Hartmann, again using large doses of diiodotyrosine (4).With the aid of I13i-labeled diiodotyrosine of high specific activity and of filter paper chromatography (Fig. l), we have studied the metabolic fate of small doses of free diiodotyrosine, both in isolated tissues and in the intact animal.Our findings indicate that both deamination and deiodination play a role in the metabolism of added diiodotyrosine by liver and kidney tissue.In the case of thyroid tissue, however, added diiodotyrosine is not deaminated, but is readily deiodinated.