In humans, the major pathway in the metabolism of the thyroid hormones consists of the removal of iodine or deiodination. Three deiodinase isoenzymes, encoded on three distinct genes, catalyze the reductive deiodination. All three enzymes contain the rare amino acid seleno-cysteine. The essential trace element selenium therefore plays an important role in thyroid hormone economy.
The most important pathway for the metabolism of T4 is monodeiodination. The removal of an iodide from the outer ring of T4 yields T3. Since the affinity of nuclear TRs is much higher for T3 than T4, outer ring mon-odeiodination of T4 to yield T3 produces a more active metabolite. Conversely, removal of an iodide from the inner ring of T4 yields an inactive metabolite, rT3. Both T3 and rT3 may undergo subsequent deiodinations to yield totally deiodinated thyronine (T0).
Up to 80% of the circulating T3 originates from deiodination of T4. This is due mainly to a deiodinase (D1) activity in the liver, where most of the T3 formed is exported into the circulation. Monodeiodination of T4 to yield T3 is catalyzed by another deiodinase (D2). It appears that D2 catalyzes T3 from T4 for local cellular demands independent of circulating T3. The third enzyme involved in the reductive deiodination of T4, T3, and other iodothyronines is D3. The sole action of this enzyme is the removal of iodide from the inner ring of iodothyronines.
The three deiodinases have differing tissue distributions, substrate preferences, and Km values. This arrangement allows for control of thyroid hormone action at the cellular level. The source and quantity of T3
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