Sandbox Reserved 1650: Difference between revisions

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[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two  [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.
[https://en.wikipedia.org/wiki/Thyroglobulin Human thyroglobulin (TG)] is a precursor of two  [https://en.wikipedia.org/wiki/Thyroid_hormones thyroid hormones] (TH): tetraiodothyronine or [[thyroxine]] (T4) and [[triiodothyronine (T3)]], essential for '''growth''', '''development''' and the '''control of metabolism'''. Its structure is essential for the diagnosis, treatment and monitoring of thyroid-related diseases.


'''PDBID''': 6scj.
[https://www.rcsb.org/sequence/6SCJ/ See the complete sequence.]


== Composition and 3D structure <ref>DOI 32025030</ref> ==
== Composition and 3D structure <ref>DOI 32025030</ref> ==
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=== Expression of the TG gene===
=== Expression of the TG gene===
In  humans, TG is coded by a large gene roughly '''300 kb long''', located on chromosome 8. The number of exons has been estimated to be around 48, each of which is separated by introns varying in size up to 64 kb. TG gene expresion is controlled positively  by '''thyro-tropin (TSH)''' through the modulation of the intra-cellular levels of '''cyclic adenosine monophosphate (cAMP)''' via its receptor (TSHr) located at the basal membrane of the cell.<ref>PMID: 11581009</ref>
In  humans, TG is coded by a large gene roughly '''300 kb long''', located on chromosome 8. The number of exons has been estimated to be around 48, each of which is separated by introns varying in size up to 64 kb. TG gene expression is controlled positively  by '''thyro-tropin (TSH)''' through the modulation of the intra-cellular levels of '''cyclic adenosine monophosphate (cAMP)''' via its receptor (TSHr) located at the basal membrane of the cell.<ref>PMID: 11581009</ref>


=== Post-translational modifications ===
=== Post-translational modifications ===
TG also undergoes N-glycosylations in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum/ endoplasmic reticulum] at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. TG also undergoes maturation steps in this organelle, where it acquires dilsufide-bonds. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.
TG also undergoes N-glycosylations in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum] at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. TG also undergoes maturation steps in this organelle, where it acquires dilsufide-bonds. These modifications enhance its stability and solubility. Indeed, the two monomers are linked not by covalent interactions but via numerous interactions allowed by these N-glycosylations.


=== Folding ===
=== Folding ===
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== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref name="jeso"/> ==
== Interest in the medical field<ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref name="jeso"/> ==
=== Modification of the TG quantity related to the desease ===
=== Modification of the TG quantity related to the disease ===
A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>
A healthy subject has between '''5 and 25 µg of TG per liter''' of blood.<ref>DOI 5773064</ref> In case of thyroid dysfunction, this level may increase or decrease. For example, it decreases in the case of congenital athyreosis (insufficiency of the thyroid gland) or prior to a miscarriage due to the presence of anti-TG antibodies, but increases in the case of cancer, thyroiditis, inflammation of the thyroid or autoimmune thyroid diseases '''AITD''' <ref>DOI 24147207</ref>(Grave's disease, Hashimoto's thyroiditis).<ref>DOI 11788684</ref><ref>DOI 17614775</ref>
   
   
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The variation of the quantity of TG can thus be as much a cause as a consequence of disease.<ref>DOI 17201802</ref>
The variation of the quantity of TG can thus be as much a cause as a consequence of disease.<ref>DOI 17201802</ref>


=== Use of TG to treat deseases ===
=== Use of TG to treat diseases ===
A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/3'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid
A classic '''TSH-stimulated''' <scene name='86/868183/Tg/3'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Tg/4'>TG</scene> measurement allows to control its rate in a more or less sensitive way and therefore to detect a disease like those mentioned above, to ensure the effectiveness of a treatment and the absence of recurrence and to avoid
miscarriages.<ref>DOI 3681445</ref>
miscarriages.<ref>DOI 3681445</ref>
Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.
Since serum <scene name='86/868183/Tg/3'>TG</scene> levels are correlated with the volume of thyroid tissue, we can also estimate the mass of thyroid tissue to detect '''hyperthyroidism''', a disease related to an enlarged thyroid or, conversely, '''hypothyroidism'''.
   
   
For example, [https://en.wikipedia.org/wiki/Thyroidectomy/ thyroidectomy] and a iodine-131 therapy can be performed to cure thyroid cancer with an 80% chance. Following removal and iodine-131 therapy, thyroglobulin is this time produced by malignant thyrocytes. As a result, its blood level is indistinguishable from that of a healthy person. <ref>PMID: 762873</ref><ref>DOI 21649472</ref>
For example, [https://en.wikipedia.org/wiki/Thyroidectomy thyroidectomy] and a iodine-131 therapy can be performed to cure thyroid cancer with an 80% chance. Following removal and iodine-131 therapy, thyroglobulin is this time produced by malignant thyrocytes. As a result, its blood level is indistinguishable from that of a healthy person. <ref>PMID: 762873</ref><ref>DOI 21649472</ref>
But in case of recurrence and persistence of cancer, its level can increase again. Thyroglobulin therefore always serves as a tumor marker allowing us to estimate the risk of recurrence (>2ng/ml) or persistence (>1ng/ml) or remission.<ref>DOI 10.1677/ERC-10-0292</ref>
But in case of recurrence and persistence of cancer, its level can increase again. Thyroglobulin therefore always serves as a tumor marker allowing us to estimate the risk of recurrence (>2ng/ml) or persistence (>1ng/ml) or remission.<ref>DOI 10.1677/ERC-10-0292</ref>


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