Figure 1.

Synthesis of TH. TG is synthesized in the endoplasmic reticulum and secreted into the colloid in the process of exocytosis. The active transport of I^- to follicular cells is carried out by sodium-iodide TSH-dependent symporter protein. The Na/I symporter draws 2 Na⁺ and 1 I^- into the cell. I^- are secreted into the colloid by the pendrin transporter. I^-, which is necessary for TH biosynthesis, is oxidized by thyroid peroxidase (TPO) in the presence of high concentrations H₂O₂ and forms molecular iodine (I₂). It reacts with Tyr residues in organification reaction leading to MIT and DIT coupling. They subsequently conjugate to form T4 with 2xDIT combination and T3 with MIT+DIT combination. These reactions also need TPO and H₂O₂. H₂O₂ is necessary for TPO action and is formed in the colloid through NADPH oxidases (DUOX subfamily). Next, TG is transported by endocytosis into the cell where it undergoes proteolysis and releases T3 and T4. TG is “recycled” and used for further TH synthesis. The TH are transported from the cell to the blood by the monocarboxylate transporter (MCT).