72 by: Heli Patel

Student – Heli Patel

Name of Enzyme: Thyroid Peroxidase

E.C. number: 1.11.1.8

Where is the enzyme found? Thyroid peroxidase (TPO) is the glycosylated heme-containing enzyme found in the apical membrane of thyroid follicular cells. The enzyme is expressed mainly in the thyroid, where it is secreted into colloids.  Thyroid peroxidase has several different isoforms, which vary by size and location within the cell.

What does the enzyme do? Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, plays a central role in the function of the thyroid gland, a butterfly-shaped tissue in the lower neck. Thyroid peroxidase catalyzes iodide oxidation to form iodine atoms. The chemical reactions catalyzed by thyroid peroxidase occur on the outer apical membrane surface and are mediated by hydrogen peroxide. Thyroid peroxide assists the chemical reaction that adds iodine to a protein called thyroglobulin, a critical step in which are added onto tyrosine residues on thyroglobulin to produce thyroxine or triiodothyronine (thyroid hormones). Thyroid hormones play an important role in regulating growth, brain development, metabolism, and the rate of chemical reactions in the body. To function properly, thyroid peroxidase must be located in the cell membrane of certain thyroid cells, called follicular cells. Also, thyroid peroxidase is a frequent epitope of autoantibodies in autoimmune thyroid disease, with such antibodies being called anti-thyroid peroxidase antibodies. This is most commonly associated with Hashimoto’s thyroiditis.

Any other interesting facts or important information on your enzyme? Thyroid peroxidase is a protein located in the apical plasma membrane of thyroid follicular cells, with its catalytic domain facing the colloid space. Thyroid peroxide is a key target in autoimmune thyroid disorders like Hashimoto’s thyroiditis and Graves’ disease, where antibodies against TPO can lead to hypothyroidism. TPO requires iodine and hydrogen peroxide to function, and its activity can be inhibited by environmental toxins and certain plant compounds. Mutations in the TPO gene can result in congenital hypothyroidism, highlighting its critical role in development and metabolism. Thyroid peroxidase is inhibited by the thioamide drugs, such as propylthiouracil and methimazole.

References

1. Habza-Kowalska, E.; Gawlik-Dziki, U.; Dziki, D. Mechanism of Action and Interactions between Thyroid Peroxidase and Lipoxygenase Inhibitors Derived from Plant Sources. Biomolecules 2019, 9 (11), 663. https://doi.org/10.3390/biom9110663 (accessed on Oct 16, 2024).
2. U.S. National Library of Medicine. TPO gene: Thyroid peroxidase. https://medlineplus.gov/genetics/gene/tpo/#conditions (accessed Oct 17, 2024).
3. Kessler, J.; Obinger, C.; Eales, G. Factors Influencing the Study of Peroxidase-Generated Iodine Species and Implications for Thyroglobulin Synthesis. Thyroid 2008, 18 (7), 769–774. https://doi.org/10.1089/thy.2007.0310 (accessed Oct 17, 2024).
4. Ferreira, A. C.; Neto, J. C.; da Silva, A. C.; Kuster, R. M.; Carvalho, D. P. Inhibition of Thyroid Peroxidase by Myrcia uniflora Flavonoids. Chem. Res. Toxicol. 2006, 19 (3), 351–355. https://doi.org/10.1021/tx0501684 (accessed Oct 17, 2024).