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
4cit.jpg
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 reactionEdit

L-Tyrosin + I− + H+ + H2O2 ⇒ 3-Iod-L-Tyrosin + 2 H2O

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

3-Iod-L-Tyrosin + I− + H+ + H2O2 ⇒ 3,5-Diiod-L-Tyrosin + 2 H2O

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

FunctionEdit

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 inhibitionEdit

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 significanceEdit

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 useEdit

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

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 Metasyntactic variable, which is released under the 
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