Update on intrathyroidal iodine metabolism

The thyroid concentrates iodide from the serum and oxidizes it at the apica l membrane, attaching it to tyrosyl residues within thyroglobulin (Tg) to m ake diiodotyrosine and monoiodotyrosine. Major players in this process are Tg, thyroperoxidase (TPO), hydrogen peroxide, pendrin, and nicotinamide ade nine dinucleotide phosphate (NADPH). Further action of TPO, hydrogen peroxi de (H2O2), and iodinated Tg produce thyroxine (T-4) and triiodothyronine (T -3) Hormone-containing Tg is stored in the follicular lumen, then processed , most commonly by microyinocytosis. The lysosomal enzymes cathepsins B, L, and D are active in Tg proteolysis. Tg digestion leaves T-4 and T-3 intact , to be released from the cell, while the 3,5'-diiodotyrosine (DIT) and 3-i odotyrosine (MIT) are retained and deiodinated for recycling within the thy roid. Some areas of especially active recent research include: (1) the role of molecular chaperones in directing properly folded TPO and Tg to the api cal membrane; (2) details of proteolytic pathways; (3) modulation of iodine metabolism, not only by thyrotropin (TSH) but by iodine supply and by feed back effects of Tg, glutathione, and inhibitory elements in the N-terminal region of Tg; and (4) details of Tg structure and iodotyrosyl coupling. Des pite general agreement on the major steps in intrathyroidal iodine metaboli sm, new details of mechanisms are constantly being uncovered and are greatl y improving understanding of the overall process.