74 by: Presly Kitamura

Student – Presly Kitamura

Enzyme: Thyroid peroxidase – also called Thyroperoxidase, or TPO

E.C. Number: 1. 11. 1. 1-14

In the human body, the thyroid peroxidase enzyme is encoded by the TPO gene located on chromosome 2p25. Thyroid peroxidase is a 933-residue transmembrane homodimer enzyme,
anchored to the apical membrane of thyroid follicle cells in the thyroid gland. The thyroid is a butterfly shaped gland located at the front of the neck, just under the larynx, and lies against and around the trachea.

Thyroid peroxidase is a critical enzyme involved in the process of thyroid hormone synthesis. Specifically, the synthesis of triiodothyronine (T3) and thyroxine (T4) from a protein made by the thyroid called thyroglobulin (Tg). Mediated by hydrogen peroxide, TPO catalyzes two key reactions: the oxidation of iodide ions to form iodine, and the coupling of iodotyrosine residues [monoiodotyrosine (MIT) and diiodotyrosine (DIT)] to form T3 and T4. These hormones play a major role in the regulation of weight, temperature, energy levels, metabolism, and the growth of skin hair and nails, making them a vital component of the endocrine system.

● Thyroid peroxidase is a major autoantigen (self-antigen that can trigger autoimmune response in the body). If antibodies attack your thyroid, they can cause serious thyroid
diseases such as Hashimoto’s disease or Grave’s disease.
● Hashimoto’s disease, also called Hashimoto’s thyroiditis, is the most common cause of hypothyroidism. Hypothyroidism (underactive thyroid) happens when the thyroid does not make enough hormones to sustain normal bodily functions, many of which slow down. Some symptoms of Hashimoto’s disease include weight gain, hair loss, and extreme fatigue.
● On the other hand, another disease caused by antibodies attacking the thyroid is Grave’s disease. Grave’s disease is the most common cause of hyperthyroidism (overactive thyroid), causing the thyroid to produce more thyroid hormones than needed. This causes many bodily functions to speed up, resulting in symptoms such as weight loss, tremors, anxiety and increased heart rate.
● The thyroid peroxidase antibody test is a blood test that is performed to help determine if an individual has a thyroid disease caused by an immune system condition. People with
TPO antibodies do not necessarily have thyroid disease, however, it is common for pregnant women to take this test because individuals who have TPO antibodies before pregnancy have a higher risk of thyroid disease after pregnancy than those who do not have the antibodies.

References

Baker, S., et al. (2023). Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies. Journal of Molecular Endocrinology, 70(3). https://doi.org/10.1530/jme-22-0149

Chen, J., et al. (2014). Metal Coordination Chemistry in the Study of Biological Pathway and Processes: A Review. International Journal of Pharmaceutical, Biological and Chemical
Sciences (IJPBCS), 3(3), 36-45. https://www.researchgate.net/publication/323236331_METAL_COORDINATION_CHE MISTRY_IN_THE_STUDY_OF_BIOLOGICAL_PATHWAY_AND_PROCESSES_A_REVIEW

Gardas, A., et al. (1997). Human Thyroid Peroxidase (TPO) Isoforms, TPO-1 and TPO-2: Analysis of Protein Expression in Graves’ Thyroid Tissue. The Journal of Clinical Endocrinology & Metabolism, 82(11), 3752–3757. https://doi.org/10.1210/jcem.82.11.4335

Godlewska, L. & Banga, P. J. (2019). Thyroid peroxidase as a dual active site enzyme: Focus on biosynthesis, hormonogenesis and thyroid disorders of autoimmunity and cancer.
Biochimie, 160, 35-45. https://doi.org/10.1016/j.biochi.2019.02.003

Habza-Kowalska, E., et al. (2019, June 22). Thyroid Peroxidase Activity Is Inhibited by Phenolic Compounds-Impact of Interaction. MDPI, Multidisciplinary Digital Publishing Institute.
www.mdpi.com/1420-3049/24/15/2766

In brief: How does the thyroid gland work? (2024, May 28). InformedHealth.org – NCBI Bookshelf. Institute for Quality and Efficiency in Health Care (IQWiG). https://www.ncbi.nlm.nih.gov/books/NBK279388/

Thyroglobulin. (2022, December 14). MedlinePlus – National Library of Medicine (US). https://medlineplus.gov/lab-tests/thyroglobulin/#:~:text=Thyroglobulin%20is%20a%20pr otein%20that,type%20of%20tumor%20marker%20test

Thyroid and parathyroid hormones. (2022, January 24). Endocrine Society. https://www.endocrine.org/patient-engagement/endocrine-library/hormones-and-endocrin
e-function/thyroid-and-parathyroid-hormones#:~:text=The%20thyroid%20gland%20releases%20triiodothyronine,part%20of%20the%20endocrine%20system

Thyroid antibodies. (2020, June 24). MedlinePlus – National Library of Medicine (US). https://medlineplus.gov/heartattack.html

UniProt. (n.d.). Thyroid peroxidase (P07202). UniProt. https://www.uniprot.org/uniprotkb/P07202/entry

Williams, D. E., et al. (2020). Structural Studies of Thyroid Peroxidase Show the Monomer Interacting With Autoantibodies in Thyroid Autoimmune Disease. Endocrinology, 161(2). https://doi.org/10.1210/endocr/bqaa016