The rate-limiting step in thyroid hormone biosynthesis is the iodination of tyrosine residues on thyroglobulin within the thyroid follicles. This process involves the enzyme thyroperoxidase (TPO), which catalyzes the oxidation of iodide (I-) to iodine (I2) and the iodination of tyrosine residues on thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Subsequent coupling of two DIT molecules or one MIT with one DIT molecule leads to the formation of the thyroid hormones triiodothyronine (T3) and thyroxine (T4), respectively.
Since the availability of iodine is crucial for the production of thyroid hormones, the activity of TPO and the supply of iodine play a pivotal role in regulating the synthesis of T3 and T4. Any disruption in the iodination process, such as iodine deficiency or TPO enzyme dysfunction, can impair the production of thyroid hormones and lead to thyroid disorders. Therefore, the iodination step mediated by TPO is considered the rate-limiting step in the biosynthesis of thyroid hormones.