Thyroid peroxidase

iodide peroxidase
Identifiers
EC number 1.11.1.8
CAS number 9031-28-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
thyroid peroxidase
Identifiers
Symbol TPO
Entrez 7173
HUGO 12015
OMIM 606765
RefSeq NM_175722
UniProt P07202
Other data
EC number 1.11.1.8
Locus Chr. 2 pter-p24

Thyroid peroxidase or thyroperoxidase (TPO) is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones.[1] In humans, thyroperoxidase is encoded by the TPO gene.[2]

Catalyzed reaction

+ I− + H+ + H2O2 ⇒ + 2 H2O

Iodide is oxidized to iodine radical which immediately reacts with tyrosine.

+ I− + H+ + H2O2 ⇒ + 2 H2O

The second iodine atom is added in similar manner to the reaction intermediate 3-iodotyrosine.

Function

Thyroid hormone synthesis, with thyroid peroxidase performing the oxidation step seen at center-left in the image.[3]

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.[4] 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.

TPO is inhibited by the thioamide drugs, such as propylthiouracil and methimazole.[5] In laboratory rats with insufficient iodine intake, genistein has demonstrated inhibition of TPO.[6]

Clinical significance

Thyroid peroxidase is a frequent epitope of autoantibodies in autoimmune thyroid disease, with such antibodies being called anti-thyroid peroxidase antibodies (anti-TPO antibodies). This is most commonly associated with Hashimoto's thyroiditis. Thus, an antibody titer can be used to assess disease activity in patients that have developed such antibodies.[7][8]

Diagnostic use

In diagnostic immunohistochemistry, the expression of thyroid peroxidase (TPO) is lost in papillary thyroid carcinoma.[9]

References

  1. ↑ 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.
  2. ↑ 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. doi:10.1073/pnas.84.16.5555. PMC 298901. PMID 3475693.
  3. ↑ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
  4. ↑ 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.
  5. ↑ Nagasaka A, Hidaka H (July 1976). "Effect of antithyroid agents 6-propyl-2-thiouracil and 1-methyl-2-mercaptoimidazole on human thyroid iodine peroxidase". J. Clin. Endocrinol. Metab. 43 (1): 152–8. doi:10.1210/jcem-43-1-152. PMID 947933.
  6. ↑ Doerge DR, Sheehan DM (June 2002). "Goitrogenic and estrogenic activity of soy isoflavones". Environ. Health Perspect. 110 Suppl 3: 349–53. doi:10.1289/ehp.02110s3349. PMC 1241182. PMID 12060828.
  7. ↑ 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. doi:10.3109/08830180009088514. PMID 11129117.
  8. ↑ 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.
  9. ↑ Tanaka T, Umeki K, Yamamoto I, Sugiyama S, Noguchi S, Ohtaki S (1996). "Immunohistochemical loss of thyroid peroxidase in papillary thyroid carcinoma: strong suppression of peroxidase gene expression". J. Pathol. 179 (1): 89–94. doi:10.1002/(SICI)1096-9896(199605)179:1<89::AID-PATH546>3.0.CO;2-R. PMID 8691351.

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