L-thyroxine(T4)

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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

Image:Iodothyronine deiodinase.png
Transformations
Template:Clear

[edit] References

<references/>


Pubchem(5819)

Lipinski’s “Rule of Five” for Thyroxine
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

List of PDB file having T4 as Ligand
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
Physiochemical Properties
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
Toxicity
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
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