Triiodothyronine
467048
222880840
2008-07-01T15:49:09Z
165.124.253.50
/* Effects of T3 */
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| ImageFile = Triiodothyronine.svg
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| IUPACName = ''(2S)''-2-amino-3- [4-(4-hydroxy-3-iodo-phenoxy)- 3,5-diiodo-phenyl]propanoic acid
| OtherNames = triiodothyronine<br>T<sub>3</sub><br>[[cytomel]]<br>3,3',5-triiodo-<small>L</small>-thyronine
| Section1 = {{Chembox Identifiers
| CASNo = 6893-02-3
| PubChem =
| SMILES = N[C@@H](Cc1cc(I)c(Oc2ccc(O)c(I)c2)<br>c(I)c1)C(O)=O
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| Section2 = {{Chembox Properties
| Formula = C<sub>15</sub>H<sub>12</sub>I<sub>3</sub>NO<sub>4</sub>
| MolarMass = 650.9776 g mol<sup>−1</sup>
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| Section3 = {{Chembox Hazards
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'''Triiodothyronine''', [[carbon|C<sub>15</sub>]][[hydrogen|H<sub>12</sub>]][[iodine|I<sub>3</sub>]][[nitrogen|N]][[oxygen|O<sub>4</sub>]], also known as '''T<sub>3</sub>''', is a [[thyroid hormone]].
[[Thyroid-stimulating hormone]] (TSH) activates the production of tetraiodothyronine (T<sub>4</sub>) and T<sub>3</sub>. This process is under regulation. In the [[hypothalamus]], T<sub>4</sub> is converted to T<sub>3</sub>. TSH is inhibited mainly by T<sub>3</sub>. The thyroid gland releases greater amounts of T<sub>4</sub> than T<sub>3</sub>, so plasma concentration of T<sub>4</sub> are 40-fold higher than those T<sub>3</sub>. Most the circulating T<sub>3</sub> is formed peripherally by deiodination of T<sub>4</sub> (85%), a process that involves the removal of iodine from carbon 5 on the outer ring of T<sub>4</sub>. Thus, T<sub>4</sub> acts as prohormone for T<sub>3</sub>.
This [[thyroid hormone]] is similar to [[thyroxine]] but with one fewer [[iodine]] [[atom]] per [[molecule]]. In addition, T<sub>3</sub> exhibits greater activity and is produced in smaller quantity.
It is the most powerful [[thyroid hormone]], and affects almost every process in the body, including [[body temperature]], [[growth]], and [[heart rate]].
== Production of T<sub>3</sub> ==
T<sub>3</sub> is metabolically active hormone that is produced from T<sub>4</sub>. T<sub>4</sub> is deiodiated by two deiodinases to produce the active triiodothyronine:<br />
1. '''Type I''' present within the liver and accounts for 80% of the deiodination of T<sub>4</sub> <br />
2. '''Type II''' present within the pitiutary.<br /><br />
T<sub>4</sub> is synthesised in the thyroid gland follicular cells as follows.<br />
1. The Na<sup>+</sup>/I<sup>-</sup> symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is secondary active transporter that utilises the concentraition gradient of Na<sup>+</sup> to move I<sup>-</sup> against its concentration gradient.<br />
2. I<sup>-</sup> is moved across the apical membranae into the colloid of the follicle.<br />
3. Thyroperoxidase oxidises two I<sup>-</sup> to form I<sub>2</sub>. Iodide is unreactive and only the more reactive iodine is required for the next step.<br />
4. The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesis in the ER of the follicular cell and secreted into the colloid.<br />
5. Thyroid stimulating hormone (TSH) released from the pituitary gland binds the TSH receptor ( a G<sub>s</sub> protein coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.<br />
6. The endosytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T<sub>4</sub> from the iodinated thyroglobulin.<br />
7. These vesicles are then exocytosed releasing the thyroid hormones.<br /><br />
In the follicullar lumen, [[tyrosine]] residues become iodinated. This reaction requires hydrogen peroxide. Iodine bonds carbon 3 or carbon 5 of tyrosine residues of thyroglobulin in a process called organification of iodine. The iodination of specific tyrosines yields monoiodotyrosine (MIT) and diiodotyrosine (DIT). One MIT and one DIT are enzymatically coupled to form T<sub>3</sub>. The enzyme is thyroid [[peroxidase]].
[[image:Iodothyronine_deiodinase.png|thumb|400px|left|Synthesis]]<br style="clear:left;"/>
== Transport of Triiodothyronine ==
The T<sub>3</sub> (and T<sub>4</sub>) bind to nuclear receptors, thyroid receptors. However, T<sub>3</sub> (and T<sub>4</sub>) are not very lipophilic and as a result, are unable to pass through the phospholipid bilayers. They therefore have specific transport proteins on the cell membranes of the effector organs which allow the T<sub>3</sub> and T<sub>4</sub> to pass into the cells. The thyroid receptors bind to response elements in gene promoters and thus enabling them to activate or inhibit transcription. The sensitivity of a tissue to T<sub>3</sub> is modulated through the thyroid receptors.
== Mechanism of Action ==
T<sub>3</sub> and T<sub>4</sub> are carried in the blood bound to plasma proteins. This has the effect of increasing the [[half life]] of the hormone and decreasing the rate at which it is taken up by peripheral tissues. There are three main proteins that the two hormones are bound to. Thyronine binding globulin (TBG) is a gylcoprotein that has a higher affinity for T<sub>4</sub> than for T<sub>3</sub>. The second plasma protein to which the hormone bind is transthyretin (which has a higher affinity for T<sub>3</sub> than for T<sub>4</sub>. Both hormones bind with a low affinity to [[albumin]], but due to the large availability of albumin it has a high capacity.
== Effects of T<sub>3</sub> ==
T<sub>3</sub> increases the [[basal metabolic rate]] and thus increases the body's oxygen and energy consumption. The basal metabolic rate is the minimal caloric requirement needed to sustain life in a resting individual. T<sub>3</sub> acts on the majority of tissues within the body, with a few exceptions including the brain, spleen and testis. It increases the production of the Na<sup>+</sup>/K<sup>+</sup> -ATPase and in general increases the turnover of different endogenous macromolcules by increasing their synthesis and degradation.<br /><br />
'''Protein'''<br />T<sub>3</sub> stimulates the production of [[RNA Polymerase]] I and II and therefore increases the rate of protein synthesis. It also increases the rate of protein degradation and in excess the rate of protein degradation exceeds the rate of protein synthesis. In such situations the body may go into negative ion balance.<br /><br />
'''Glucose'''<br /> T<sub>3</sub> potentiates the effects of the β-adrenergic receptors on the metabolism of glucose. It therefore increases the rate of glycogen breakdown and glucose synthesis in [[gluconeogenesis]]. It also potentiates the effects of [[insulin]], which have opposing effects.<br /><br />
'''Lipids'''<br />T<sub>3</sub> stimulates the breakdown of cholesterol and increases the number of LDL receptors, therefore increasing the rate of lipolysis.<br /><br />
T<sub>3</sub> also affects the cardiovascular system. It increases the caridac output by increasing the heart rate and force of contraction. This results in increased [[systolic blood pressure]] and decreased [[diastolic blood pressure]]. The latter two effects act to produce the typical bounding pulse seen in hyperthyroidism.<br /><br />
T<sub>3</sub> also has profound effect upon the developing embryo and infants. It affects the lungs and influences the postnatal growth of the central nervous system. It stimulates the production of [[myelin]], [[neurotransmitters]] and axon growth. It is also important in the linear growth of bones.
== The effects of abnormal thyroid functions ==
'''[[Goitre]]'''<br />
''Goitre is the swelling of the thryoid gland''. <br />It is often associated with iodine deficiency. The lack of iodine decreases the production of the thyroid hormones T<sub>3</sub> and T<sub>4</sub>. These hormones usually act on the pituitary gland to decrease the realease of thyroid stimulating hormone(TSH) by negative feedback. Lack of this feedback causes the systemic levels of TSH to increase. One of the actions of TSH (aside from stimulating the release of the thyroid hormones) is to stimulate the growth of the thyroid gland. However, usually the enlarged thyroid will then act normally to trap sufficient iodine and thus the levels of T<sub>3</sub> and T<sub>4</sub> are normal.<br />
Goitre may also be a result of Grave's disease or of a tumour.
<br /><br />
'''[[Hyperthyroidism]]'''<br />
''High levels of T<sub>3</sub>''<br />. The symptoms of hyperthyroidism include:<br />
* Raised basal metabolic rate<br />
* Bounding pulse<br />
* Heat intolerance<br />
* Weight loss (often accompanied by increased appetite)<br />
* Increased sympathetic drive<br />
* Eye protrusion<br />
Hyperthryoidism may be caused by Grave's disease, an autoimmune disease where [[immunoglobulins]] that resemble TSH cause constituitive release of high levels of the thyroid hormones. On the other hand it may be due to a tumour of the thyroid gland.<br /><br />
'''[[Hypothyroidism]]'''<br />
''Low levels of T<sub>3</sub>''<br />
If this occurs during childhood it can result in gross deficiencies of myelination of the central nervous system neurons and stunting of growth due to decreased growth of the long bones. Hypothyroidism in the adult is known as [[myxoedema]], a condition where a reduced metabolism, slow mentation, hypotermia and constipation are seen (due the lack of gut motility stimulated by T<sub>3</sub>). A cause of hyothyroidism is thryoid hormone deficiency, a genetic defect that reduces the hormone binding.
{{organic-compound-stub}}
{{Hormones}}
[[Category:Iodinated tyrosine derivatives]]
[[Category:Thyroid hormones]]
[[cs:Trijodthyronin]]
[[de:Triiodthyronin]]
[[nl:Trijodothyronine]]
[[ja:トリヨードサイロニン]]
[[pl:Trójjodotyronina]]
[[sl:Trijodtironin]]
[[sv:Trijodtyronin]]