Which enzyme catalyzes the iodination of tyrosyl residues in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)?

Explanation

## Thyroid Hormone Synthesis — Iodination Step **Key Point:** Thyroid peroxidase (TPO) is the critical enzyme that catalyzes the iodination of tyrosyl residues within thyroglobulin, converting them to MIT (one iodine) and DIT (two iodines). This is the first committed step in thyroid hormone synthesis. ### Mechanism of TPO Action **High-Yield:** TPO requires: - H~2~O~2~ as the oxidizing agent (generated by NADPH oxidase) - Thyroglobulin as the substrate - Iodide (I^−^) as the iodine source The reaction occurs in the colloid space and is catalyzed at the apical membrane of thyroid follicular cells. ### Coupling Reaction After iodination, TPO also catalyzes the **coupling** of MIT and DIT residues: - DIT + DIT → T~4~ (thyroxine) - DIT + MIT → T~3~ (triiodothyronine) **Clinical Pearl:** TPO is the primary autoantigen in Hashimoto's thyroiditis; anti-TPO antibodies are highly specific for autoimmune thyroid disease. ### Why TPO Is Essential | Step | Enzyme | Product | |------|--------|----------| | Iodide uptake | Na^+^/I^−^ symporter (NIS) | Intracellular I^−^ | | Iodination | **Thyroid peroxidase** | **MIT + DIT** | | Coupling | **Thyroid peroxidase** | **T~3~ + T~4~** | | Secretion | Proteolysis | Free T~3~ + T~4~ | [cite:Guyton & Hall Physiology 14e Ch 76]