The Mechanism of Iodination Reactions in Thyroid Glands¹

Previous studies from this laboratory showed that inorganic iodide is oxidized by H2O2 and an enzyme, iodide peroxidase, before it is incorporated into tyrosine and protein by thyroid and salivary homogenates. It is reported here that several other naturally occurring biological oxidants or electron carriers cannot replace H2O2, although it had been shown elsewhere that flavin cofactors stimulate iodide utilization by thyroid preparations. The results of this study demonstrate that catalase or anaerobiosis prevent flavin activation, and thus support the conclusion that the activation is due to the production of H2O2 during autoxidation of the flavin. The peroxidases of salivary and thyroid glands are not identical because a homogenate of salivary gland will oxidize bromide and slightly incorporate it into tyrosine, but thyroid homogenates will not. Neither tissue oxidizes chloride or fluoride. Histidine is iodinated by thyroid and salivary extracts but tyrosine is overwhelmingly iodinated when both amino acids are present. Although iodohistidine has been isolated from thyroid glands, it has not previously been biosynthesized in vitro. Under conditions where tyrosine is readily iodinated, possible thyroxine precursors, thyronine, di- and tri-iodothyronine, are not iodinated by rat or human thyroid extracts. A suggestion for the in vitro role of Cu++ in iodine metabolism is presented.