Radioactive Iodine as an Indicator of the Metabolism of Iodine

The early discovery that physiological activity’in the thyroid gland was associated with an iodoprotein (1, 2) led logically to investigations of the physiological effects and chemical properties of various proteins or protein fractions that had been subjected to artificial iodination. In 193334, Abelin et al. observed physiological effects resembling those produced by the thyroid gland after the administration of fractions obtained by hydrolysis of iodinated protein (3, 4). It was not until 1939, however, that Ludwig and von Mutzenbecher (5) clearly demonstrated the isolation of crystalline thyroxine from the following proteins after treatment with molecular iodine: casein, serum albumin, serum globulin, silk fibroin, and edestin. The chemical identity of thyroxine was established by elementary analysis, determination of physical and chemical properties, and by the preparation of thyronine by catalytic hydrogenation of the thyroxine. These workers also obtained diiodotyrosine and monoiodotyrosine from these iodinated proteins. The isolation of crystalline diiodotyrosine, however, from a hydrolysate of iodocasein had been reported earlier (1910) by Oswald (6), whereas the preparation of thyroxine from iodinated casein was later (1939) confirmed by Harington and Rivers (7). Interestingly enough, von Mutzenbecher (8) has further shown that thyroxine is formed when diiodotyrosine is incubated with NaOH for 14 days, an observation that has received recent confirmation from Block (9) and Johnson and Tewkesbury (10). The latter (10) have also shown that pyruvic acid is a product of this reaction and on the basis of this finding have proposed a possible mechanism to explain the formation of thyroxine. Since the early work of Abelin, physiological effects closely resembling thyroid activity have repeatedly been observed to follow the administration of iodinated protein and fractions of their hydrolysates (11-14). But