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Thyroid peroxidase, also called thyroperoxidase ( TPO), thyroid specific peroxidase or iodide peroxidase, is an expressed mainly in the where it is secreted into colloid. Thyroid peroxidase oxidizes ions to form atoms for addition onto residues on for the production of (T4) or (T3), the . In humans, thyroperoxidase is encoded by the TPO .


Function
Inorganic iodine enters the body primarily as iodide, I. After entering the (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 after which thyroid peroxidase iodide to atomic iodine (I) or iodinium (I+). The chemical reactions catalyzed by thyroid peroxidase occur on the outer apical membrane surface and are mediated by hydrogen peroxide.

The "organification of iodine", the incorporation of iodine into 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. Ascidians (tunicates or sea squirts) and amphioxus, which are close invertebrate relatives of vertebrates, have a primitive homolog of the thyroid known as the . They do not have a thyroglobulin gene that produce a protein intended specifically for making thyroxine, but do produce thyroxine. Presumably they simply rely on the nonspecific action.


Catalyzed reaction
The reactions registered with Enzyme Commission no. 1.11.1.8 are:
  1. Conversion of iodide to diiodine, 2 I + H2O2 + 2 H+ = I2 + 2 H2O
  2. Generation of 3-iodo-tyrosine, thyroglobulin-L-tyrosine + I + H2O2 + H+ = thyroglobulin-3-iodo-L-tyrosine + 2 H2O
  3. Generation of 3,5-iodo-tyrosine, thyroglobulin-3-iodo-L-tyrosine + I + H2O2 + H+ = thyroglobulin-3,5-diiodo-L-tyrosine + 2 H2O
  4. Coupling to produce T4, 2 thyroglobulin-3,5-diiodo-L-tyrosine + H2O2 = thyroglobulin-L-thyroxine + thyroglobulin- + 2 H2O
  5. Coupling to produce T3, thyroglobulin-3-iodo-L-tyrosine + thyroglobulin-3,5-diiodo-L-tyrosine + H2O2 = thyroglobulin-3,3',5-triiodo-L-thyronine + thyroglobulin-dehydroalanine + 2 H2O

However, in light of the non-specific organification by TPO, it would be useful to distinguish which actions are the "true" functions of TPO. Under the model of Kessler et al. (2008), the real functions of TPO are:

  • Conversion of iodide to diiodine, as in reaction (1) above. The I2 produced would go on to react with OH to form , which reacts with the tyrosyl residue on proteins such as thyroglobulin, explaining the reactions (2) and (3) above.
  • Generation of free radicals from tyrosyl, 3-iodotyrosyl (MIT), and 3,5-diiodotyrosyl (DIT) residues or their free forms. These free radicals couple with iodized proteins (such as thyroglobulin-3,5-diiodo-L-tyrosine) to perform reactions (4) and (5).

Both actions are mediated by the oxidized form of TPO, TPO-O, produced by reaction of TPO with hydrogen peroxide.


Side reactions
T3 is produced when a MIT free radical couples to a DIT residue on a protein. Coupling of DIT to MIT in the opposite order yields a substance, r-T3, which is biologically inactive. and T1 are also known to occur naturally.


Stimulation and inhibition
TPO is stimulated by TSH, which upregulates gene expression.

TPO is inhibited by the drugs, such as and . In laboratory rats with insufficient iodine intake, has demonstrated inhibition of TPO.


Clinical significance
Thyroid peroxidase is a frequent of 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 can be used to assess disease activity in patients that have developed such antibodies.


Diagnostic use
In diagnostic immunohistochemistry, the expression of thyroid peroxidase (TPO) is lost in papillary thyroid carcinoma.


Biotechnology
TPO's ability to non-selectively couple tyrosine residues together has been used to modify .


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