Thyroid peroxidase

Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, 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]

iodide peroxidase
iodide peroxidase monomer, Zobellia galactanivorans
Identifiers
EC number1.11.1.8
CAS number9031-28-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
thyroid peroxidase
Identifiers
SymbolTPO
NCBI gene7173
HGNC12015
OMIM606765
RefSeqNM_175722
UniProtP07202
Other data
EC number1.11.1.8
LocusChr. 2 pter-p24

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]

gollark: ```c int apio[100] = {0,1,0,0,0,1,0,0,0,1,0,1,0,1,0,1,0,1,0,0,0,1,0,1,0,1,0,1,1,0,0,1,0,1,0,1,0,1,0,0,0,1,0,1,0,1,0,1,0,1,0,1,0,1,0,1,0,1,0,0,0,1,0,1,0,1,0,1,1,0,0,1,0,1,0,1,0,1,0,0,0,1,0,1,0,1,0,1,0,1,0,0,0,1,0,0,0,1,0,0};```
gollark: `3 3 3 3 3 3 3 3 3 2 2 1 1 1 1 1 1 1 1 1 2 2 3 3 3 3 3 3 3 3 3 2 2 1 1 1 1 1 1 1 1 1 2 2 3 2 3 3 4 3 3 2 3 3 4 3 3 2` is the output on the basic case I used.
gollark: Yep, it works.
gollark: Is what I would say if I didn't have a good test suite, but I have a basic one.
gollark: I don't have a good test suite for C.

References
  1. Ruf J, Carayon P (Jan 2006). "Structural and functional aspects of thyroid peroxidase". Archives of Biochemistry and Biophysics. 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 (Aug 1987). "Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs". Proceedings of the National Academy of Sciences of the United States of America. 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 (Jul 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 (Jul 1976). "Effect of antithyroid agents 6-propyl-2-thiouracil and 1-mehtyl-2-mercaptoimidazole on human thyroid iodine peroxidase". The Journal of Clinical Endocrinology and Metabolism. 43 (1): 152–8. doi:10.1210/jcem-43-1-152. PMID 947933.
  6. Doerge DR, Sheehan DM (Jun 2002). "Goitrogenic and estrogenic activity of soy isoflavones". Environmental Health Perspectives. 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". International Reviews of Immunology. 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 (Jun 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 (May 1996). "Immunohistochemical loss of thyroid peroxidase in papillary thyroid carcinoma: strong suppression of peroxidase gene expression". The Journal of Pathology. 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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