Which of the following enzymes catalyzes the iodination of tyrosine residues in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)?

Explanation

## Thyroid Peroxidase (TPO) — The Key Enzyme in Iodination **Key Point:** Thyroid peroxidase (TPO) is the critical enzyme that catalyzes the incorporation of iodine into tyrosine residues within thyroglobulin, forming MIT and DIT in the thyroid follicular lumen. ### Mechanism of TPO Action TPO catalyzes the **oxidative iodination** of tyrosine residues using H₂O₂ as the electron acceptor and iodide (I⁻) as the substrate. This occurs on the apical membrane of thyroid follicular cells and is essential for thyroid hormone synthesis. ### The Iodination Pathway 1. Iodide (I⁻) is oxidized to iodine (I₂) by TPO 2. Iodine attaches to the 3-position of the tyrosine ring → **monoiodotyrosine (MIT)** 3. Further iodination at the 5-position → **diiodotyrosine (DIT)** 4. Coupling of MIT + DIT → T₃ (triiodothyronine) 5. Coupling of DIT + DIT → T₄ (thyroxine) **High-Yield:** TPO is the primary target of autoimmune thyroid disease (Hashimoto's thyroiditis). Anti-TPO antibodies are the most common thyroid autoantibodies and are highly specific for autoimmune thyroiditis. **Clinical Pearl:** Propylthiouracil (PTU) and methimazole inhibit TPO, making them first-line antithyroid drugs in hyperthyroidism. [cite:Guyton & Hall Textbook of Medical Physiology Ch 76]