Triiodothyronine
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| Triiodothyronine | |
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| IUPAC name | (2S)-2-amino-3- [4-(4-hydroxy-3-iodo-phenoxy)- 3,5-diiodo-phenyl]propanoic acid |
| Other names | triiodothyronine T3 cytomel 3,3',5-triiodo-L-thyronine |
| Identifiers | |
| CAS number | [6893-02-3] |
| SMILES | N[C@@H](Cc1cc(I)c(Oc2ccc(O)c(I)c2) c(I)c1)C(O)=O |
| Properties | |
| Molecular formula | C15H12I3NO4 |
| Molar mass | 650.9776 g mol−1 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references |
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Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone.
Thyroid-stimulating hormone (TSH) activates the production of tetraiodothyronine (T4) and T3. This process is under regulation. In the hypothalamus, T4 is converted to T3. TSH is inhibited mainly by T3. The thyroid gland releases greater amounts of T4 than T3, so plasma concentration of T4 are 40-fold higher than those T3. Most the circulating T3 is formed peripherally by deiodination of T4 (85%), a process that involves the removal of iodine from carbon 5 on the outer ring of T4. Thus, T4 acts as prohormone for T3.
This thyroid hormone is similar to thyroxine but with one fewer iodine atom per molecule. In addition, T3 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.
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[edit] Production of T3
T3 is metabolically active hormone that is produced from T4. T4 is deiodiated by two deiodinases to produce the active triiodothyronine:
1. Type I present within the liver and accounts for 80% of the deiodination of T4
2. Type II present within the pitiutary.
T4 is synthesised in the thyroid gland follicular cells as follows.
1. The Na+/I- 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+ to move I- against its concentration gradient.
2. I- is moved across the apical membranae into the colloid of the follicle.
3. Thyroperoxidase oxidises two I- to form I2. Iodide is unreactive and only the more reactive iodine is required for the next step.
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.
5. Thyroid stimulating hormone (TSH) released from the pituitary gland binds the TSH receptor ( a Gs protein coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
6. The endosytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
7. These vesicles are then exocytosed releasing the thyroid hormones.
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 T3. The enzyme is thyroid peroxidase.
[edit] Transport of Triiodothyronine
The T3 (and T4) bind to nuclear receptors, thyroid receptors. However, T3 (and T4) 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 T3 and T4 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 T3 is modulated through the thyroid receptors.
[edit] Mechanism of Action
T3 and T4 are carried in the blood bound to plasma proteins. This has two it effects it increases the half life of the hormone but also decreases the rate at which it is taken up by the peripheral tissues. There are three main protein that the two hormones are bound to. Thyronine binding globulin (TBG) is a gylcoprotein that has a higher affinity for T4 than for T3. The sedond plasma protein to which the hormone bind is transthyretin (which has a higher affinity for T3 than for T4. Both hormones bind with a low affinity to albumin, but due to the large availability of albumin it has a high capacity.
[edit] Effects of T3
T3 ac to increase the basal metabolic rate and thus increases the oxygen and energy consumption. The basal metabolic rate is the minimal calorific requirement needed to sustain life in a resting individual. It acts on the majority of tissues within the body, with a few exceptions including the brain, spleen and testis. It increaese the production of the Na+/K+ -ATPase and general increases the turnover of different endogenous macromolcules by increasing their synthesis and degradation.
Protein
T3 stimulates the production fo RNA Polymerase I and II and therefore increase the rate of protein synthesis. It also increases the rate of protein degradation and in excess the rate of proeitn degradation exceeds the rate of protein synthesis. In such situations the body goes into negative ion balance.
Glucose
T3 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 aslo potentiates the effects of insulin, which have opposing effects.
Lipids
T3 stimulates the breakdown of cholesterol and increase the number of LDL receptors and therefore increases the rate of lipolysis.
T3 also affects the cardiovascular system. It acts increase the caridac aoutput increase the heart rate, force of contraction, increase systolic blood pressure and decrease the diastolic blood pressure. The later two effects act to produce the typical bounding pulse seen in hyperthyroidism.
T3 also has profound effect upon the developing embryo and infants. It affects te 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.
[edit] The effects of abnormal thyroid functions
Goitre
Goitre is the swelling of the thryoid gland.
It is often associated with iodine deficiency. The lack of iodine decreases the production of the thyroid hormones T3 and T4. 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 T3 and T4 are normal.
Goitre may also be a result of Grave's disease or of a tumour.
Hyperthyroidism
High levels of T3
. The symptoms of hyperthyroidism include:
•Raised basal metabolic rate
•Bounding pulse
•Heat intolerance
•Weight loss (often accompanied by increased appetite)
•Increased sympathetic drive
•Eye protrusion
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.
Hypothyroidism
Low levels of T3
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 T3). A cause of hyothyroidism is thryoid hormone deficiency, a genetic defect that reduces the hormone binding.
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