iodide peroxidase
iodide peroxidase monomer, Zobellia galactanivorans
Identifiers
EC no.	1.11.1.8
CAS no.	9031-28-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDBPDBePDBsum
Gene Ontology	AmiGO /QuickGO
Search PMC articles PubMed articles NCBI proteins

Thyroid peroxidase, also calledthyroperoxidase (TPO),thyroid specific peroxidase oriodide peroxidase, is anenzyme expressed mainly in thethyroid where it is secreted into colloid. Thyroid peroxidase oxidizesiodide ions to formiodine atoms for addition ontotyrosine residues onthyroglobulin for the production ofthyroxine (T₄) ortriiodothyronine (T₃), thethyroid hormones.^[1] In humans, thyroperoxidase is encoded by theTPOgene.^[2]

Inorganic iodine enters the body primarily as iodide, I⁻. After entering thethyroid 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 viapendrin after which thyroid peroxidaseoxidizes 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 intothyroglobulin 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 theendostyle. 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.^[4]

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]-dehydroalanine + 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 Kessleret al. (2008), the real functions of TPO are:^[4]

• Conversion of iodide to diiodine, as in reaction (1) above. The I₂ produced would go on to react with OH⁻ to formHOI, 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.^[4]

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.^[5][6]T₂ andT₁ are also known to occur naturally.^[7]

TPO is stimulated byTSH, which upregulates gene expression.

TPO is inhibited by thethioamide drugs, such aspropylthiouracil andmethimazole.^[8] In laboratory rats with insufficient iodine intake,genistein has demonstrated inhibition of TPO.^[9]

Thyroid peroxidase is a frequentepitope ofautoantibodies in autoimmune thyroid disease, with such antibodies being calledanti-thyroid peroxidase antibodies (anti-TPO antibodies). This is most commonly associated withHashimoto's thyroiditis. Thus, anantibody titer can be used to assess disease activity in patients that have developed such antibodies.^[10][11]

In diagnosticimmunohistochemistry, the expression of thyroid peroxidase (TPO) is lost inpapillary thyroid carcinoma.^[12]

TPO's ability to non-selectively couple tyrosine residues together has been used to modifyprotein tags.^[13]

• Thyroid+Peroxidase at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 2
• EC 1.11.1
• Thyroid

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