Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
expressed mainly in the
thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
where it is secreted into colloid. Thyroid peroxidase oxidizes
iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine de ...
ions to form
iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
atoms for addition onto
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
residues on
thyroglobulin
Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
for the production of
thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
(T
4) or
triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3 and its prohormone thyroxine ...
(T
3), the
thyroid hormones
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
.
In humans, thyroperoxidase is encoded by the ''TPO''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Catalyzed reaction
+ I
− + H
+ + H
2O
2 ⇒
+ 2 H
2O
Iodide is oxidized to iodine radical which immediately reacts with tyrosine.
+ I
− + H
+ + H
2O
2 ⇒
+ 2 H
2O
The second iodine atom is added in similar manner to the reaction intermediate 3-iodotyrosine.
Function
Inorganic iodine enters the body primarily as iodide, I
−. After entering the
thyroid follicle
Thyroid follicular cells (also called thyroid epithelial cells or thyrocytes) are the major cell type in the thyroid gland, and are responsible for the production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). They ...
(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
Pendrin is an anion exchange protein that in humans is encoded by the ''SLC26A4'' gene (solute carrier family 26, member 4).
Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studies showing that i ...
, after which thyroid peroxidase
oxidize
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
s iodide to atomic iodine (I) or iodinium (I
+). The "organification of iodine," the incorporation of iodine into
thyroglobulin
Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
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.
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
A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R–CS–NR′R″, where R, R′, and R″ are organic groups. They are analogous to amides but they exhibit greater multiple bond ch ...
drugs, such as
propylthiouracil and
methimazole.
In laboratory rats with insufficient iodine intake,
genistein
Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen.
It was first isolated in 1899 from the dyer's bro ...
has demonstrated inhibition of TPO.
Clinical significance
Thyroid peroxidase is a frequent
epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
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
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
. Thus, an
antibody titer can be used to assess disease activity in patients that have developed such antibodies.
Diagnostic use
In diagnostic
immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
, the expression of thyroid peroxidase (TPO) is lost in
papillary thyroid carcinoma
Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases.Chapter 20 in: 8th edition. It occurs more frequently in women and presents in th ...
.
References
External links
*
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EC 1.11.1
Thyroid