The iodide peroxidase o thyroid peroxidase (TPO) is a heme-glycoprotein belonging to the family of mammalian peroxidases (such as myeloperoxidase, lactoperoxidase and others) that participates in the thyroid hormone synthesis pathway.
Its main function is the "iodination" of tyrosine residues in thyroglobulin, and the formation of 3-3'-5-triiodothyronine (T3) and thyroxine (T4) through a "coupling" reaction. intramolecular of iodinated tyrosines.
Triiodothyronine and thyroxine are two hormones produced by the thyroid gland that have essential functions in mammalian development, differentiation, and metabolism. Its mechanism of action depends on the interaction of its nuclear receptors with specific gene sequences of its target genes..
The existence of the enzyme iodide peroxidase was confirmed in the 1960s by different authors and considerable advances have now been made in determining its structure, its functions and the characteristics of the gene that encodes it. in different organisms.
In much of the literature related to this enzyme, it is known as the microsomal "autoantigen" and is related to some autoimmune thyroid diseases..
Thanks to its immunogenic characteristics, this enzyme is a target or target molecule for the antibodies present in the serum of many patients with thyroid pathologies and its defects can lead to hormonal deficiencies that can be important pathophysiologically speaking.
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Iodide peroxidase is encoded by a gene located on chromosome 2 in humans, which measures more than 150 kbp and is composed of 17 exons and 16 introns..
This transmembrane protein, with a single segment immersed in the membrane, is closely related to myeloperoxidase, with whom it shares more than 40% amino acid sequence similarity.
Its synthesis occurs in polyribosomes (a set of ribosomes that is responsible for the translation of the same protein) and is then inserted into the membrane of the endoplasmic reticulum, where it undergoes a process of glycosylation.
Once synthesized and glycosylated, iodide peroxidase is transported to the apical pole of thyrocytes (thyroid cells or thyroid cells), where it is able to expose its catalytic center to the follicular lumen of the thyroid..
Expression of the gene encoding thyroid peroxidase or iodide peroxidase is controlled by thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.
The genetic elements that allow increasing or enhancing the expression of this gene in humans have been described in the regions that flank the 5 'end of it, usually between the first 140 base pairs of this "flanking" region..
There are also elements that repress or decrease the expression of this protein, but unlike "enhancers", these have been described downstream of the gene sequence..
Much of the regulation of the genetic expression of iodide peroxidase occurs in a tissue-specific manner, and this depends on the action of DNA-binding elements that act on cis, such as TTF-1 transcription factors and others.
This protein with enzymatic activity has around 933 amino acid residues and an extracellular C-terminal end of 197 amino acids long that comes from the expression of other gene modules that code for other glycoproteins..
Its molecular weight is around 110 kDa and is part of the group of type 1 glycosylated transmembrane proteins, since it has a glycosylated transmembrane segment and a heme group in its active site..
The structure of this protein has at least one disulfide bridge in the extracellular region that forms a characteristic closed loop that is exposed on the surface of thyrocytes..
The main physiological function of iodide peroxidase is related to its participation in the synthesis of thyroid hormone, where it catalyzes the “iodination” of tyrosine residues of monoiodotyrosine (MIT) and diiodotyrosine (DIT), in addition to the coupling of the iodotyrosine residues in thyroglobulin.
In order to understand the function of the thyroid peroxidase enzyme, it is necessary to consider the steps of hormonal synthesis where it participates:
1-It begins with the transport of iodide to the thyroid and continues with
2-The generation of an oxidizing agent such as hydrogen peroxide (H2O2)
3-Subsequently, a receptor protein is synthesized, thyroglobulin
4-The iodide is oxidized to a higher valence state and then
5-Iodide binds to tyrosine residues present in thyroglobulin
6-In thyroglobulin iodothyronines (a type of thyroid hormones) are formed by coupling of iodotyrosine residues
7-Thyroglobulin is stored and cleaved, then
8-The iodine is removed from the free iodotyrosines and, finally,
9-Thyroxine and triiodothyronine are released into the blood; These hormones exert their effects by interacting with their specific receptors, which are located on the nuclear membrane and which are capable of interacting with target DNA sequences, functioning as transcription factors..
As could be deduced from the knowledge of the functions of the two hormones in whose synthesis it participates (T3 and T4), iodide peroxidase has important implications at the physiological level..
The lack of both hormones during human development produces defects in growth and mental retardation, as well as metabolic imbalances in adult life.
Iodide peroxidase is one of the main thyroid autoantigens in humans and is associated with complement system-mediated cytotoxicity. Its function as an autoantigen is highlighted in patients with thyroid autoimmune diseases.
Gout disease, for example, is due to a deficiency in the iodine content during hormone synthesis in the thyroid, which in turn has been related to a deficiency in iodination of thyroglobulin as a result of certain defects in iodide peroxidase..
Some carcinomas are characterized by having altered iodide peroxidase functions, that is, the activity levels of this enzyme are significantly lower than in non-cancer patients.
However, studies have confirmed that it is a highly variable characteristic, which depends not only on the patient, but also on the type of cancer and the regions affected..
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