Thyroid peroxidase or thyroperoxidase (TPO) is an enzyme mainly expressed in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3) (thyroid hormones).[1] In humans, thyroperoxidase is encoded by the TPO gene.[2]
Function
Inorganic iodine enters the body primarily as iodide, I-. After entering the thyroid follicle (or thyroid follicular cell) via a Na+/I- symporter (NIS) on the basolateral side, iodide is shuttled across the apical membrane into the colloid via pendrin, after which thyroid peroxidase oxidizes iodide to atomic iodine (I) or iodinium (I+). The "organification of iodine," the incorporation of iodine into thyroglobulin for the production of thyroid hormone is nonspecific, that is, there is no TPO bound intermediate, but iodination occurs via reactive iodine species released from TPO.[3] The chemical reactions catalyzed by thyroid peroxidase occur on the outer apical membrane surface and are mediated by hydrogen peroxide.
Stimulation and inhibition
TPO is stimulated by TSH, which upregulates gene expression. It is inhibited by the thioamide drugs, such as propylthiouracil and methimazole.[4]
Clinical significance
It is a frequent epitope of autoantibodies in autoimmune thyroid disease (most commonly, Hashimoto's thyroiditis) so the antibody titer can be used to assess disease activity in patients who have developed such antibodies.[5][6]
References
- ^ Ruf J, Carayon P (January 2006). "Structural and functional aspects of thyroid peroxidase". Arch. Biochem. Biophys. 445 (2): 269–77. doi:10.1016/j.abb.2005.06.023. PMID 16098474.
- ^ Kimura S, Kotani T, McBride OW, Umeki K, Hirai K, Nakayama T, Ohtaki S (August 1987). "Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs". Proc. Natl. Acad. Sci. U.S.A. 84 (16): 5555–9. PMID 3475693. PMC: 298901. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3475693.
- ^ Kessler J, Obinger C, Eales G (July 2008). "Factors influencing the study of peroxidase-generated iodine species and implications for thyroglobulin synthesis". Thyroid 18 (7): 769–74. doi:10.1089/thy.2007.0310. PMID 18631006.
- ^ Nagasaka A, Hidaka H (July 1976). "Effect of antithyroid agents 6-propyl-2-thiouracil and 1-mehtyl-2-mercaptoimidazole on human thyroid iodine peroxidase". J. Clin. Endocrinol. Metab. 43 (1): 152–8. PMID 947933.
- ^ McLachlan SM, Rapoport B (2000). "Autoimmune response to the thyroid in humans: thyroid peroxidase--the common autoantigenic denominator". Int. Rev. Immunol. 19 (6): 587–618. PMID 11129117.
- ^ Chardès T, Chapal N, Bresson D, Bès C, Giudicelli V, Lefranc MP, Péraldi-Roux S (June 2002). "The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases". Immunogenetics 54 (3): 141–57. doi:10.1007/s00251-002-0453-9. PMID 12073143.
External links
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