Thyroglobulin
Encyclopedia
Thyroglobulin is a 660 kDa, dimeric protein
produced by and used entirely within the thyroid
gland. In earlier literature, Tg was referred to as colloid
.
Thyroglobulin should not be confused with Thyroxine-binding globulin
, a carrier protein
responsible for carrying the thyroid hormones in the blood.
s thyroxine
(T4) and triiodothyronine
(T3). The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase (which has been referred to as tetraiodothyronine 5' deiodinase). It is presumed that Tg and thyroid are also an important storage of iodine for all body needs, in particular, for many iodine-concentrating organs such as breast, stomach, salivary glands, thymus, etc.
(see iodine in biology
).
In fact, the Tg molecule, which contains approximately 120 tyrosyl residues, is able to form only very small amounts of thyroid hormone (5-6 molecules of T4 and T3).
Tg is produced by the thyroid epithelial cells, called thyrocytes, which form spherical follicles. Tg is secreted and stored in the follicular lumen.
Via a reaction with the enzyme
thyroperoxidase, iodine is covalently bound to tyrosine
residues in thyroglobulin molecules, forming monoiodotyrosine
(MIT) and diiodotyrosine
(DIT).
Small globules of the follicular colloid (Tg) are endocytosed (hormone (TSH)-mediated) and protease
s in lysosome
s digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm. The T3 and T4 are then transported across (TSH-mediated) the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism while the lysosome is recycled back to the follicular lumen.
or Graves' disease
frequently develop antibodies against Tg. Tg-specific antibodies help in the diagnosis of these diseases, but they also may be present in apparently healthy euthyroid
individuals.
Thyroglobulin levels in the blood can be used as a tumor marker
for certain kinds of thyroid cancer
(particulary papillary or follicular thyroid cancer). Thyroglobulin levels in the blood can also be elevated in cases of Graves' disease
.
with Binding immunoglobulin protein
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
produced by and used entirely within the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
gland. In earlier literature, Tg was referred to as colloid
Colloid
A colloid is a substance microscopically dispersed evenly throughout another substance.A colloidal system consists of two separate phases: a dispersed phase and a continuous phase . A colloidal system may be solid, liquid, or gaseous.Many familiar substances are colloids, as shown in the chart below...
.
Thyroglobulin should not be confused with Thyroxine-binding globulin
Thyroxine-binding globulin
Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...
, a carrier protein
Carrier protein
Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
responsible for carrying the thyroid hormones in the blood.
Function
Tg is used by the thyroid gland to produce the thyroid hormoneThyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
(T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....
(T3). The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase (which has been referred to as tetraiodothyronine 5' deiodinase). It is presumed that Tg and thyroid are also an important storage of iodine for all body needs, in particular, for many iodine-concentrating organs such as breast, stomach, salivary glands, thymus, etc.
(see iodine in biology
Iodine in biology
Iodine is an essential trace element for life, the heaviest element commonly needed by living organisms, and the second-heaviest known to be used by any form of life .-The thyroid:Iodine's main role in animal biology is as constituents of the thyroid hormones, thyroxine and...
).
In fact, the Tg molecule, which contains approximately 120 tyrosyl residues, is able to form only very small amounts of thyroid hormone (5-6 molecules of T4 and T3).
Via a reaction with the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
thyroperoxidase, iodine is covalently bound to tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
residues in thyroglobulin molecules, forming monoiodotyrosine
Monoiodotyrosine
Monoiodotyrosine is a precursor of thyroid hormone and results from iodization of tyrosine at the meta- position of the phenol ring.Two units can combine to form 3,3'-diiodothyronine. One unit can combine with diiodotyrosine to form triiodothyronine, as occurs in the colloid of the thyroid...
(MIT) and diiodotyrosine
Diiodotyrosine
Diiodotyrosine is a precursor of thyroid hormone and results from iodization of monoiodotyrosine at the other meta- position on the phenol ring....
(DIT).
- ThyroxineThyroxineThyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
is produced by combining two moieties of DIT. - TriiodothyronineTriiodothyronineTriiodothyronine, C15H12I3NO4, 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....
is produced by combining one molecule of MIT and one molecule of DIT.
Small globules of the follicular colloid (Tg) are endocytosed (hormone (TSH)-mediated) and protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s in lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
s digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm. The T3 and T4 are then transported across (TSH-mediated) the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism while the lysosome is recycled back to the follicular lumen.
Clinical significance
Patients with Hashimoto's thyroiditisHashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
or Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...
frequently develop antibodies against Tg. Tg-specific antibodies help in the diagnosis of these diseases, but they also may be present in apparently healthy euthyroid
Euthyroid
Euthyroid is the state of having normal thyroid gland function.Examples of a nonfunctioning thyroid gland may be hypothyroidism, hyperthyroidism, or thyroiditis....
individuals.
Thyroglobulin levels in the blood can be used as a tumor marker
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...
for certain kinds of thyroid cancer
Thyroid cancer
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...
(particulary papillary or follicular thyroid cancer). Thyroglobulin levels in the blood can also be elevated in cases of Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...
.
Interactions
Thyroglobulin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Binding immunoglobulin protein
Binding immunoglobulin protein
Binding immunoglobulin protein also known as 78 kDa glucose-regulated protein or heat shock 70 kDa protein 5 is a HSP70 molecular chaperone located in the lumen of the endoplasmic reticulum that binds newly-synthesized proteins as they are translocated into the ER, and maintains them in a state...
.