L-thyroxine(T4)
From DrugPedia: A Wikipedia for Drug discovery
Thyroxine, or 3,5,3',5'-tetraiodothyronine (often abbreviated as T4), a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland.
Synthesis
The hormone was synthesised in 1927 by British chemists Charles Robert Harington and George Barger.
Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.
T4 is transported in blood, with 99.95% of the secreted T4 being protein bound, principally to thyroxine-binding globulin (TBG), and, to a lesser extent, to transthyretin and serum albumin. T4 is involved in controlling the rate of metabolic processes in the body and influencing physical development. Administration of thyroxine has been shown to significantly increase the concentration of nerve growth factor in the brains of adult mice.<ref>Walker et al. (27 April 1979) Thyroxine increases nerve growth factor concentration in adult mouse brain. Science. Vol. 204, No. 4391. pp. 427 - 429.</ref>
Note: Thyroxine is a prohormone and a reservoir for the active thyroid hormone triiodothyronine (T3). T4 is converted in the tissues by deiodinases to T3. The "D" isomer is called "Dextrothyroxine"<ref>Template:MeshName</ref> and is used as a lipid modifying agent.<ref>Template:ATC</ref> The half-life of thyroxine once released into the blood circulatory system is about 1 week.
[edit] Reactions
- Template:ClearImage:Iodothyronine deiodinase.pngTransformations
[edit] References
<references/>
Pubchem(5819)
| 4 | 3 | 2 | 1 | 0 |
|---|---|---|---|---|
| GOOD | INDETERMINATE | INDETERMINATE | INDETERMINATE | POOR |
KEGG Pathway(C01829)
- Tyrosine metabolism
- Neuroactive ligand-receptor interaction
- Autoimmune thyroid disease
Comment Thyroid hormone synthesized on thyroglobulin
| MMDB ID | PDB ID | Reference |
|---|---|---|
| 18746 | 1ICT | Wojtczak A, Luft JR, Cody VStructural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complexJ. Biol. Chem. v268, p.6202-6206 |
| 19209 | 1IE4 | Wojtczak ACrystal structure of rat transthyretin at 2.5 A resolution: first report on a unique tetrameric structureActa Biochim. Pol. v44, p.505-517 |
| 22897 | 1HK1 | Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry SStructural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemiaProc. Natl. Acad. Sci. U. S. A. v100, p.6440-6445 |
| 22898 | 1HK2 | Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry SStructural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemiaProc. Natl. Acad. Sci. U. S. A. v100, p.6440-6445 |
| 22893 | 1HK3 | Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry SStructural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemiaProc. Natl. Acad. Sci. U. S. A. v100, p.6440-6445 |
| 22900 | 1HK4 | Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry SStructural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemiaProc. Natl. Acad. Sci. U. S. A. v100, p.6440-6445 |
| 22901 | 1HK5 | Petitpas I, Petersen CE, Ha CE, Bhattacharya AA, Zunszain PA, Ghuman J, Bhagavan NV, Curry SStructural basis of albumin-thyroxine interactions and familial dysalbuminemic hyperthyroxinemiaProc. Natl. Acad. Sci. U. S. A. v100, p.6440-6445 |
| 28581 | 1SN0 | Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AEHigh resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxineJ. Biol. Chem. v279, p.26411-26416 |
| 3173 | 1Y0X | Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Cunha Lima ST, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JDThyroxine-thyroid hormone receptor interactionsJ. Biol. Chem. v279, p.55801-55808 |
| 5764 | 2CEO | Zhou A, Wei Z, Read RJ, Carrell RWStructural mechanism for the carriage and release of thyroxine in the bloodProc. Natl. Acad. Sci. U. S. A. v103, p.13321-13326
The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family of protease inhibitors, thyroxine-binding globulin (TBG) and corticosteroid-binding globulin. The structure of TBG bound to tetra-iodo thyroxine, solved here at 2.8 A, shows how the thyroxine is carried in a surface pocket on the molecule.... |
| 5764 | 2ROX | Wojtczak A, Luft JR, Cody VStructural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complexJ. Biol. Chem. v268, p.6202-6206 |
| 67282 | 2RIW | Description The Reactive Loop Cleaved Human Thyroxine Binding Globulin Complexed With Thyroxine.
Deposition: Zhou A, Wei Z, Stanley PLD, Read RJ, Stein PE, Carrell RW, 2007/10/12 |
| 898 | 1ETA | Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen LThe x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolutionJ. Biol. Chem. v268, p.2416-2424 |
| 899 | 1ETB | Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen LThe x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolutionJ. Biol. Chem. v268, p.2416-2424 |
| Physical Property | Value | Units | Temp (deg C) | Source |
|---|---|---|---|---|
| Melting Point | 235.5 | deg C | EXP | |
| log P (octanol-water) | 4.120 | (none) | EST | |
| Water Solubility | 1.05E-04 | mg/L | 25 | EST |
| Vapor Pressure | 1.24E-17 | mm Hg | 25 | EST |
| Henry's Law Constant | 7.91E-19 | atm-m3/mole | 25 | EST |
| Atmospheric OH Rate Constant | 4.17E-11 | cm3/molecule-sec | 25 | EST |
| Organism | Test Type | Route | Reported Dose (Normalized Dose) | Effect | Source |
|---|---|---|---|---|---|
| child | TDLo | oral | 328ug/kg (0.328mg/kg) | CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP,VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION | Pediatrics. Vol. 73, Pg. 313, 1984.Link to PubMed |
| man | TDLo | oral | 63ug/kg (0.063mg/kg) | PTIONS",CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP | Journal of Toxicology, Clinical Toxicology. Vol. 20, Pg. 517, 1983.,Link to PubMed |
| man | TDLo | oral | 10286ug/kg (10.286mg/kg) | BEHAVIORAL: EXCITEMENT,CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP,
GASTROINTESTINAL: NAUSEA OR VOMITING | Veterinary and Human Toxicology. Vol. 41, Pg. 323, 1999.Link to PubMed |
| women | TDLo | oral | 400ug/kg/2D-I (0.4mg/kg) | BEHAVIORAL: COMA,CARDIAC: ARRHYTHMIAS (INCLUDING CHANGES IN CONDUCTION) | Intensive Care Medicine. Vol. 13, Pg. 33, 1987.Link to PubMed |
