Sandbox Reserved 1650: Difference between revisions

Line 40:

=== Expression of the TG gene===

Thyroid follicular cells synthesize human <scene name='86/868183/~~Full_tg~~/2'>TG</scene> via the TG gene on chromosome 8.

Thyroid follicular cells synthesize human <scene name='86/868183/Tg/3'>TG</scene> via the TG gene on chromosome 8.

=== Post-translational modifications ===

TG also undergoes N-glycosylations in the ER at 17 <scene name='86/868183/~~Carbohydrated~~/1'>glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. 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 ER at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. 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 ===

Line 55:

In the colloid, about 30 tyrosines out of the 66 tyrosines, each consisting of a phenol group, are iodized. The quantity of iodinated tyrosine depends however on the iodide concentration of the colloid. Indeed, one or two iodide ions can be covalently bound to the colloid and thus give a di (DIT) or mono-iodinated (MIT) phenol group. The iodination of the phenol groups is carried out by two membrane enzymes of the follicular cells: the double oxidase (DUOX) synthesizes the hydrogen peroxide H2O2 necessary for thyroid peroxidase (TPO).

Due to the spatial conformation of <scene name='86/868183/~~Full_tg~~/2'>TG</scene>, there is a transfer of di or mono iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.

Due to the spatial conformation of <scene name='86/868183/Tg/3'>TG</scene>, there is a transfer of di- or mono-iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.

At the end of the coupling, the donor tyrosines are left with a dehydroalanine.

Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/~~Full_tg~~/2'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di iodinated tyrosines.

Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/Tg/3'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di-iodinated tyrosines.

The hormone synthesis function of TG is thus particularly linked to its structure. Moreover, research shows that denaturation or a simple modification of its conformation prevents the formation of TH <ref>PMID:4710237</ref><ref>DOI 456595</ref>.

Line 68:

=== Iodine tank ===

The complex and particularly stable structure of <scene name='86/868183/~~Full_tg~~/2'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.

The complex and particularly stable structure of <scene name='86/868183/Tg/3'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.

== Interest in the medical field<ref>DOI 17614775</ref><ref>DOI 10.1677/ERC-10-0292</ref><ref>DOI 5773064</ref><ref>DOI 3681445</ref><ref>DOI 12089177</ref><ref>DOI 21134539</ref><ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref>DOI 26595189</ref> ==

=== Modification of the TG quantity related to the desease ===

A healthy subject has between 5 and 25 µg of TG per liter of blood. 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>

A healthy subject has between '''5 and 25 µg of TG per liter''' of blood. 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>

In addition, a decrease in the size or capacity of the thyroid causes a decrease in the synthesis of TH by the <scene name='86/868183/~~Full_tg~~/2'>TG</scene>, and thus a drop in the blood level of T4 and T3, which in turn causes heart disease, brain disease and abnormalities in the development of the fetus. <ref>DOI 29246752</ref><ref>DOI 28593684</ref><ref>DOI 12721190</ref>

In addition, a decrease in the size or capacity of the thyroid causes a decrease in the synthesis of TH by the <scene name='86/868183/Tg/3'>TG</scene>, and thus a drop in the blood level of T4 and T3, which in turn causes heart disease, brain disease and abnormalities in the development of the fetus. <ref>DOI 29246752</ref><ref>DOI 28593684</ref><ref>DOI 12721190</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 ===

A classic TSH-stimulated <scene name='86/868183/~~Full_tg~~/2'>TG</scene> measurement or ultrasensitive <scene name='86/868183/~~Full_tg~~/2'>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/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

miscarriages.

Since serum <scene name='86/868183/~~Full_tg~~/2'>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, 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.

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@@ Line 40: / Line 40: @@
 === Expression of the TG gene===
-Thyroid follicular cells synthesize human <scene name='86/868183/Full_tg/2'>TG</scene> via the TG gene on chromosome 8.
+Thyroid follicular cells synthesize human <scene name='86/868183/Tg/3'>TG</scene> via the TG gene on chromosome 8.
 === Post-translational modifications ===
-TG also undergoes N-glycosylations in the ER at 17 <scene name='86/868183/Carbohydrated/1'>glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. 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 ER at <scene name='86/868183/Glycosylation_sites/1'>17 glycosylation sites</scene>, so that 10% of its molecular weight is carbohydrate. 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 ===
@@ Line 55: / Line 55: @@
 In the colloid, about 30 tyrosines out of the 66 tyrosines, each consisting of a phenol group, are iodized. The quantity of iodinated tyrosine depends however on the iodide concentration of the colloid. Indeed, one or two iodide ions can be covalently bound to the colloid and thus give a di (DIT) or mono-iodinated (MIT) phenol group. The iodination of the phenol groups is carried out by two membrane enzymes of the follicular cells: the double oxidase (DUOX) synthesizes the hydrogen peroxide H2O2 necessary for thyroid peroxidase (TPO).
-Due to the spatial conformation of <scene name='86/868183/Full_tg/2'>TG</scene>, there is a transfer of di or mono iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.
+Due to the spatial conformation of <scene name='86/868183/Tg/3'>TG</scene>, there is a transfer of di- or mono-iodinated aromatic ring from a donor tyrosine to a close acceptor diiodotyrosine for the 14 tyrosines of the hormonogenic sites. Acceptor iodinated tyrosines are DITs because they are deprotonated due to their 6.5 acid pka facilitating the acceptance reaction leading to the formation of quinol-ether bonds, whereas donor iodinated tyrosines are MITs with a pKa of 8.5<ref>DOI 10.1530/eje.0.1380227</ref>.
 At the end of the coupling, the donor tyrosines are left with a dehydroalanine.
-Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/Full_tg/2'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di iodinated tyrosines.
+Once iodization and coupling have been performed, endocytosis of the colloid to the lysosome occurs. The <scene name='86/868183/Tg/3'>TG</scene> is proteolyzed by cathepsin proteases<ref>DOI 1939080</ref> and 7 TH are thus released from 14 mono- or di-iodinated tyrosines.
 The hormone synthesis function of TG is thus particularly linked to its structure. Moreover, research shows that denaturation or a simple modification of its conformation prevents the formation of TH <ref>PMID:4710237</ref><ref>DOI 456595</ref>.
@@ Line 68: / Line 68: @@
 === Iodine tank ===
-The complex and particularly stable structure of <scene name='86/868183/Full_tg/2'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.
+The complex and particularly stable structure of <scene name='86/868183/Tg/3'>TG</scene> gives it iodide reservoir properties. Indeed, all iodinated but non-hormonoid tyrosines are useful for iodine storage in the thyroid gland.
 == Interest in the medical field<ref>DOI 17614775</ref><ref>DOI 10.1677/ERC-10-0292</ref><ref>DOI 5773064</ref><ref>DOI 3681445</ref><ref>DOI 12089177</ref><ref>DOI 21134539</ref><ref>DOI 6814409</ref><ref>DOI 29984794</ref><ref>DOI 26595189</ref> ==
 === Modification of the TG quantity related to the desease ===
-A healthy subject has between 5 and 25 µg of TG per liter of blood. 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>
+A healthy subject has between '''5 and 25 µg of TG per liter''' of blood. 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>
-In addition, a decrease in the size or capacity of the thyroid causes a decrease in the synthesis of TH by the <scene name='86/868183/Full_tg/2'>TG</scene>, and thus a drop in the blood level of T4 and T3, which in turn causes heart disease, brain disease and abnormalities in the development of the fetus. <ref>DOI 29246752</ref><ref>DOI 28593684</ref><ref>DOI 12721190</ref>
+In addition, a decrease in the size or capacity of the thyroid causes a decrease in the synthesis of TH by the <scene name='86/868183/Tg/3'>TG</scene>, and thus a drop in the blood level of T4 and T3, which in turn causes heart disease, brain disease and abnormalities in the development of the fetus. <ref>DOI 29246752</ref><ref>DOI 28593684</ref><ref>DOI 12721190</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 ===
-A classic TSH-stimulated <scene name='86/868183/Full_tg/2'>TG</scene> measurement or ultrasensitive <scene name='86/868183/Full_tg/2'>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/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
 miscarriages.
-Since serum <scene name='86/868183/Full_tg/2'>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, 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.