The thyroid gland depends on TPO for normal functions which operates mainly in its follicular epithelial cells. The enzyme TPO enables thyroid hormone synthesis by transforming iodide into active iodine and allowing iodine to bind with tyrosine residues thereby generating thyroid hormone precursors.
When TPO enzyme activity becomes impaired it disrupts thyroid hormone production leading to thyroid disorders such as hypothyroidism and autoimmune diseases like Hashimoto's thyroiditis which makes the thyroid gland dependent on TPO to function properly. The TPO protein serves as an antigen which triggers certain autoimmune thyroid disease patients to develop autoantibodies against TPO.
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Structure and Function of Thyroid Peroxidase
Structural Characteristics
TPO is a member of the peroxidase superfamily functioning as a membrane-bound glycoprotein. The TPO structure includes a signal peptide region for endoplasmic reticulum targeting to enable secretion and contains a catalytic domain which conducts standard peroxidase reactions through one transmembrane segment and a short intracellular tail. The catalytic domain of TPO contains an embedded stable heme prosthetic group which enables the enzyme's oxidation reactions.
Function
TPO is a key enzyme in the synthesis of thyroid hormones (T3 and T4), which catalyzes the following reactions:
- Oxidation of iodide ions (I⁻ → I⁰)
- Tyrosine organication of iodine (forming MIT and DIT)
- Coupling reaction (MIT + DIT → T3, DIT + DIT → T4)
All these reactions occur on thyroglobulin (Tg) molecules in the lumen of thyroid follicles.
Reasons TPO Easily Affected by External Substances
Thyroid peroxidase (TPO) is synthesized by the thyroid gland which acts as a catalyst for the iodine-tyrosine reaction that forms thyroid hormones T4 and T3. TPO enzyme function depends on maintaining its structural integrity and the specific redox conditions needed for catalytic reactions. Thyroid health depends on thyroid peroxidase activity and its response to numerous internal and external factors.
Environmental Pollutants
- Environmental endocrine disruptors may block TPO activity or alter TPO expression through disruption of thyroid hormone receptors. For example, polychlorinated biphenyls (PCBs),
- Bisphenol A (BPA) together with phthalates like DEHP.
Drugs
Some medications function as direct inhibitors of TPO and block its catalytic reaction. Excessive iodine exposure results in the Wolff-Chaikoff effect which suppresses TPO activity similarly to thiourea antithyroid drugs like propylthiouracil PTU.
Autoimmune Response
The body's immune system attacks TPO during thyroid autoimmune diseases like Graves' disease or Hashimoto's thyroiditis leading to its poor performance and malfunction. When Hashimoto's thyroiditis develops TPO becomes the immune system's attack target and anti-TPO antibodies emerge in the body to disrupt normal function and induce hypothyroidism.
Nutritional Factors
The element selenium operates within glutathione peroxidase and regulates the redox environment which then influences TPO activity. TPO enzyme activity relies on iron presence in its active site where iron deficiency leads to reduced enzyme function.
Iodine Intake
The synthesis of thyroid hormones requires iodine as an essential element and both lack and excess of iodine intake can impact TPO function.
Tips for Protecting TPO Function
- Stay away from endocrine-disrupting chemicals found in plastics and some cosmetics products.
- Your diet should contain adequate amounts of trace elements and essential nutrients specifically iodine iron and selenium.
- Regular thyroid function exams are essential for people with a family history of thyroid conditions or autoimmune diseases.
Important Role of Thyroid Peroxidase
TPO enzyme activity enables thyroid hormone production which allows thyroid function to operate. TPO enzyme activates the iodination process of tyrosine molecules which results in the formation of thyroid hormones T3 and T4. Human metabolic processes and developmental growth heavily depend on thyroid hormones. TPO modifies iodine into its active state through oxidation reactions which enables it to connect with tyrosine to generate iodotyrosine necessary for thyroid hormone production.
Hashimoto's thyroiditis exemplifies how autoimmune diseases target TPO. Hypothyroidism occurs when the immune system mistakenly attacks TPO. Lithium and antithyroid drugs inhibit TPO activity to prevent thyroid hormone production. Environmental heavy metal pollution causes harm to human thyroid function and alters TPO activity. The thyroid's functionality suffers impairment when there is a deficiency of essential nutrients including selenium and zinc. may also affect the function of TPO.
Proper iodine intake is essential to keep thyroid function normal while TPO activity remains healthy through autoimmune disease prevention and drug side effect management based on strong nutritional health.
References
- Ruf, J., et al. Structural and functional aspects of thyroid peroxidase. Archives of biochemistry and biophysics. 2006, 445(2): 269-277.
- McLachlan, S., et al. Thyroid peroxidase as an autoantigen. Thyroid. 2007, 17(10): 939-948.
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