CHAPTER 10.3: The Role of Sulfur and Selenium Species in the Thyroid Check Access

In this chapter, the basic chemistry of thyroid gland involving sulfur and selenium species is described. Thyroxine (T4), the pro‐hormone, is deiodinated regioselectively by three isoforms of selenocysteine‐containing iodothyronine deiodinases (D1, D2, D3). While D1 catalyses the deiodination of T4 in both the outer and inner rings, D2 and D3 are selective to either outer‐ring (D2) or inner‐ring (D3) iodines. The deiodination of T4 by D1 produces a selenenyl iodide as intermediate, which then reacts with a thiol cofactor to produce T3 (or rT3) and unmodified enzyme. In contrast, the exact mechanism for the regioselective deiodination of thyroid hormones by D2 and D3 has not been established. Organoselenium compounds that functionally mimic the activity of deiodinases will be useful in understanding the role of sulfur/selenium in the deiodination reactions and such studies may help in the development of isoform‐specific inhibitors.