Thyroid hormone: Difference between revisions
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=== Synthesis === | === Synthesis === | ||
Thyroxine and Triiodothyronine are based on the [[Amino acid|amino acid]] [[ | Thyroxine and Triiodothyronine are based on the [[Amino acid|amino acid]] [[Tyrosine|tyrosine]] and which has been iodinated to varying degrees. | ||
Thyroid tissue is composed of distinct functional units called [[Follicles]]. These consist of a central [[Colloid]]-containing [[Lumen]] surrounded by a thin [[Epithelium|epithelium]] of follicular cells <ref>Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall</ref>. | Thyroid tissue is composed of distinct functional units called [[Follicles]]. These consist of a central [[Colloid]]-containing [[Lumen]] surrounded by a thin [[Epithelium|epithelium]] of follicular cells <ref>Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall</ref>. The follicular cells produce a [[Glycoproteins|glycoprotein]], [[thyroglobulin]], which is rich in tyrosine residues. This is [[Exocytosis|exocytosed]] into the colloid where it is stored. Tyrosine residues of thyroglobulin are iodinated to produce monoiodothyronine and diiodothyronine, the precursors to the thyroid hormones, catalysed by the enzyme [[Thyroperoxidase]]. <ref>Ruf, J., Carayon, P. (2006). "Structural and functional aspects of thyroid peroxidase." Archives of Biochemistry and Biophysics 445: 2; 269-277</ref> The iodine is provided via the [[Sodium-Iodide Symporter|Na<sup>+</sup>/<sup>-</sup>I<sup>-</sup>Symporter ]]which actively transports Sodium and Iodide ions into the follicular cells from the blood using free energy released from transporting Na<sup>+ </sup>down its concentration gradient. <ref>Li, C.C., Ho, T.Y., Kao, C.H., Wu, S.L., Liang, J.A., Hsaing, C.Y. (2010). "Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity.", Journal of Biomedical Science, 17: 89</ref> Monoiodothyronine and diiodothyronine under go a coupling reaction independant of thyroperoxidase in which the active thyroid hormones, thyroxine and triiodothyronine are yielded. | ||
=== | A coupling of monoiodothyronine and diiodothyronine yields triiodothyronine. | ||
A coupling of two diiodothyronine molecules yields thyroxine (tetraiodothyronine). | |||
Upon stimulation from [[Thyroid-Stimulating Hormone|<font color="#0066cc">Thyroid-Stimulating Hormone</font>]] the colloid is [[Pinocytosis|pinocytosed]] into the follicular cell where the thyroglobulin is degraded within the endocytotic vesicles to release the thyroid hormones. | |||
T<sub>3 </sub>and T<sub>4</sub> enter the bloodstream and is bound to carrier proteins. Only approximately 0.4% T<sub>3</sub> and 0.04% of T<sub>4 </sub>is circulated in free form. 70% of thyroid hormones are bound with high affinity to Thyroxine-Binding Globulin. 10% of T<sub>4</sub> is bound to Thyroxine-Binding Prealbumin which has a tenfold greater affinity for T<sub>4 </sub>than for T<sub>3</sub>. Around 15% of thyroid hormones are bound with low affinity to albumin which allows rapid dissociation in the tissues. | |||
=== Metabolism of T<sub>4</sub> === | |||
Around 100nM of T<sub>4</sub> are secreted every day, whereas only 5nM of the more active T<sub>3 </sub>is secreted. T<sub>4 </sub>is deiodinated to produce a greater concentration of T<sub>3</sub> in ways that both up-regulates and down-regulates the level of thyroid hormone in the blood. | |||
==== Up-Regulatory processes ==== | |||
1 5'-Deiodinase and 2 5'-Deiodinase produce T<sub>3 </sub>from T<sub>4</sub> | |||
==== Down-Regulatory processes ==== | |||
3 5'-Deiodinase produces rT<sub>3</sub>, an inactive form of T<sub>3</sub>, thus reducing the effects of active thyroid hormone. | |||
=== Effects === | |||
| |||
References | |||
<references /> | <references /> | ||
Revision as of 00:35, 10 January 2011
'Thyroid Hormone' is an umbrella term referring to Triiodothyronine, T3, and Thyroxine, T4, two Tyrosine-based hormones produced by the Thyroid gland. Their synthesis involves the iodination of two precursors, monoiodothyronine, T1, and Diiodothyronine, T2. Although thyroxine is produced in larger quantities, it must be noted that triiodothyronine is three to eight times more active. Thus, thyroxine is metabolised into triiodothyronine for active use. The thyroid hormones are involved in growth, working synergistically with growth hormone, in cellular metabolism and in bodily thermogenisis.
The level of thyroid hormones carried in the blood plasma must be regulated; over-active thyroid tissue leads to an increase in circulating thyroid hormones, termed hyperthyroidism, the symptoms of which include goitre. The converse, a deficiency of thyroid hormones, or hypothyroidism can have serious acute effects as well as chronic effects, the latter most serious when presented congenitally.
Synthesis
Thyroxine and Triiodothyronine are based on the amino acid tyrosine and which has been iodinated to varying degrees.
Thyroid tissue is composed of distinct functional units called Follicles. These consist of a central Colloid-containing Lumen surrounded by a thin epithelium of follicular cells [1]. The follicular cells produce a glycoprotein, thyroglobulin, which is rich in tyrosine residues. This is exocytosed into the colloid where it is stored. Tyrosine residues of thyroglobulin are iodinated to produce monoiodothyronine and diiodothyronine, the precursors to the thyroid hormones, catalysed by the enzyme Thyroperoxidase. [2] The iodine is provided via the Na+/-I-Symporter which actively transports Sodium and Iodide ions into the follicular cells from the blood using free energy released from transporting Na+ down its concentration gradient. [3] Monoiodothyronine and diiodothyronine under go a coupling reaction independant of thyroperoxidase in which the active thyroid hormones, thyroxine and triiodothyronine are yielded.
A coupling of monoiodothyronine and diiodothyronine yields triiodothyronine.
A coupling of two diiodothyronine molecules yields thyroxine (tetraiodothyronine).
Upon stimulation from Thyroid-Stimulating Hormone the colloid is pinocytosed into the follicular cell where the thyroglobulin is degraded within the endocytotic vesicles to release the thyroid hormones.
T3 and T4 enter the bloodstream and is bound to carrier proteins. Only approximately 0.4% T3 and 0.04% of T4 is circulated in free form. 70% of thyroid hormones are bound with high affinity to Thyroxine-Binding Globulin. 10% of T4 is bound to Thyroxine-Binding Prealbumin which has a tenfold greater affinity for T4 than for T3. Around 15% of thyroid hormones are bound with low affinity to albumin which allows rapid dissociation in the tissues.
Metabolism of T4
Around 100nM of T4 are secreted every day, whereas only 5nM of the more active T3 is secreted. T4 is deiodinated to produce a greater concentration of T3 in ways that both up-regulates and down-regulates the level of thyroid hormone in the blood.
Up-Regulatory processes
1 5'-Deiodinase and 2 5'-Deiodinase produce T3 from T4
Down-Regulatory processes
3 5'-Deiodinase produces rT3, an inactive form of T3, thus reducing the effects of active thyroid hormone.
Effects
References
- ↑ Hadley, M. E (2000) Endocrinology 5th Edition, Upper Saddle River, Prentice Hall
- ↑ Ruf, J., Carayon, P. (2006). "Structural and functional aspects of thyroid peroxidase." Archives of Biochemistry and Biophysics 445: 2; 269-277
- ↑ Li, C.C., Ho, T.Y., Kao, C.H., Wu, S.L., Liang, J.A., Hsaing, C.Y. (2010). "Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity.", Journal of Biomedical Science, 17: 89