Figure 1.

Postulated pathway of biosynthesis of 3,5-T2 from its putative precursors T4 and T3. The figure shows the structural formulas of L-T4, the prohormone, synthetized, and secreted by the thyroid gland, and its 5′-deiodination product L-T3, which is secreted in part by the thyroid gland (ca. 80%) or generated in extrathyroidal tissues by the two selenoenzyme 5-deiodinase type 1 or type 2, which both remove the 5′-iodine atom of L-T4 in a reductive two-substrate reaction with a so far unknown physiological cofactor. Indirect evidence mainly from in vivo experiments in rodents suggests that 3,5-T2, a physiologically active endogenous thyroid hormone metabolite, is formed by a further 3′-deiodination reaction also catalyze by these (one of these) two deiodinase enzymes.