The effect of manganese compounds and certain other factors on the formation of thyroxine in iodinated casein.

In experiments conducted in our laboratory during recent years it has been found that the thyroidal activity of iodinated proteins is influenced markedly by the conditions employed during their preparation. In earlier communications it has been shown that when the protein is iodinated in a mildly alkaline sodium bicarbonat,e solution a product of surprisingly high thyroidal potency is obtained by limiting the addition of iodine to the amount required to substitute 2 atoms per molecule of tyrosine in the protein (1, 2) and, secondly, by incubating the iodinated protein at the elevated temperature of 60-70” (3). It was also observed (3) that the formation of active substance was apparently catalyzed by the metals in a brass stirrer that was used in making up part of the preparations. From our own experiments (l-3) as well as those of Ludwig and von Mutzenbecher (4), Harington and Pitt Rivers (5), and Johnson and Tewkesbury (6) it was believed that the formation of thyroxine in an iodinated protein must be an oxidative process, involving the coupling of two diiodotyrosine radicals and elimination of one side chain. It thus seemed conceivable that the reaction might be expedited by use of the proper oxidative catalyst and maintenance of mildly oxidative conditions in the reaction medium. Evidence that this is true is provided by the experiments to be reported.