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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-13 18:15:41 UTC
HMDB IDHMDB00248
Secondary Accession Numbers
  • HMDB01918
Metabolite Identification
Common NameThyroxine
DescriptionThe thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature. Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles. (If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in goitre.) Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine. Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine, which is metabolized more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, which are derived from pig thyroid glands, are a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin. this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a severe drop in body temperature. The major hormone derived from the thyroid gland. 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. The thyronamines function via some unknown mechanism to inhibit neuronal activity.
Structure
Thumb
Synonyms
  1. (-)-Thyroxine
  2. 3,3',5,5''-Tetraiodo-L-thyronine
  3. 3,3',5,5'-Tetraiodo-L-thyronine
  4. 3,5,3',5'-Tetraiodo-L-Thyronine
  5. 3,5,3',5'-Tetraiodothyronine
  6. 3,5,3'5'-Tetraiodo-L-thyronine
  7. D-Thyroxine
  8. DL-Thyroxin
  9. Henning
  10. L-3,5,3',5'-Tetraiodothyronine
  11. L-Thyroxin
  12. L-Thyroxine
  13. Laevothyroxinum
  14. Levothroid
  15. Levothyroxin
  16. Levothyroxine
  17. Levothyroxine sodium
  18. Levothyroxinum
  19. Levoxyl
  20. Prestwick_548
  21. Synthroid
  22. T4
  23. Tetraiodothyronine
  24. Tetramet
  25. THX
  26. Thyratabs
  27. Thyrax
  28. Thyreoideum
  29. Thyroxin
  30. Thyroxinal
  31. Thyroxine
  32. Thyroxine I 125
  33. Thyroxine iodine
Chemical FormulaC15H11I4NO4
Average Molecular Weight776.87
Monoisotopic Molecular Weight776.686681525
IUPAC Name(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Traditional Namelevothyroxine
CAS Registry Number51-48-9
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
InChI Identifier
InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1
InChI KeyXUIIKFGFIJCVMT-LBPRGKRZSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aromatic Homomonocyclic Compounds
  • Aromatic Homopolycyclic Compounds
  • a hormone(Cyc)
  • amino acid zwitterion(ChEBI)
  • an iodoaromatic compound(Cyc)
Substituents
  • Amphetamine Or Derivative
  • Aryl Iodide
  • Carboxylic Acid
  • Iodobenzene
  • Methoxyphenol
  • Organoiodide
  • Phenethylamine
  • Phenol
  • Phenol Derivative
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point235.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.009 g/LALOGPS
logP1.15ALOGPS
logP3.73ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)0.27ChemAxon
pKa (Strongest Basic)9.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.78ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.79ChemAxon
Polarizability49.52ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Fibroblasts
  • Gonads
  • Intestine
  • Muscle
  • Myelin
  • Nerve Cells
  • Neuron
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testes
  • Thyroid Gland
Pathways
NameSMPDB LinkKEGG Link
Tyrosine MetabolismSMP00006map00350
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000009 - 0.000023 uMNot AvailableBoth
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.12 +/- 0.0061 uMChildren (1-13 years old)Both
Normal
details
BloodDetected and Quantified0.000016 (0.0000064-0.000064) uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.0000144 +/- 0.0000036 uMAdolescent (13-18 years old)FemaleNormal details
BloodDetected and Quantified0.00002 (0.00001-0.00003) uMAdult (>18 years old)BothNormal
    • Wu AHB. Tietz cli...
details
SalivaDetected and Quantified0.0 - 1.0 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.00032 +/- 0.00015 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0000185 +/- 0.0000052 uMAdult (>18 years old)BothHypothyroidism details
BloodDetected and Quantified0.057 +/- 0.0058 uMChildren (1-13 years old)BothMalnutrition (type kwashiorkor and marasmus) details
BloodDetected and Quantified0.000011 +/- 0.0000016 uMAdolescent (13-18 years old)FemaleAnorexia nervosa details
UrineDetected and Quantified0.0015 +/- 0.00154 umol/mmol creatinineAdult (>18 years old)BothProteinuria details
Associated Disorders and Diseases
Disease References
Anorexia nervosa
  1. Capo-chichi CD, Gueant JL, Lefebvre E, Bennani N, Lorentz E, Vidailhet C, Vidailhet M: Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia nervosa. Am J Clin Nutr. 1999 Apr;69(4):672-8. Pubmed: 10197568
Hypothyroidism
  1. Sjoberg S, Eriksson M, Nordin C: L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study. Eur J Endocrinol. 1998 Nov;139(5):493-7. Pubmed: 9849813
Proteinuria
  1. Chandurkar V, Shik J, Randell E: Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation. Endocr Pract. 2008 Jan-Feb;14(1):97-103. Pubmed: 18238748
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021829
KNApSAcK IDNot Available
Chemspider ID5614
KEGG Compound IDC01829
BioCyc IDL-THYROXINE
BiGG ID38499
Wikipedia LinkThyroxine
NuGOwiki LinkHMDB00248
Metagene LinkHMDB00248
METLIN ID439
PubChem Compound5819
PDB IDT44
ChEBI ID18332
References
Synthesis ReferenceMartinovich, V. P.; Katok, Ya. M.; Fil'chenkov, N. A.; Sviridov, O. V. Conjugated synthesis of L-thyroxine and L-triiodothyronine. Vestsi Natsyyanal'nai Akademii Navuk Belarusi, Seryya Khimichnykh Navuk (2004), (1), 85-92.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  2. Gil'miiarova FN, Pervova IuV, Radomskaia VM, Gergel' NI, Tarasova SV: [Levels of unified metabolites and thyroid hormones in blood and oral fluid of children with minimal brain dysfunction] Biomed Khim. 2004 Mar-Apr;50(2):204-10. Pubmed: 15179829
  3. Kahan IL, Varsanyi-Nagy M, Toth M, Nadrai A: The possible role of tear fluid thyroxine in keratoconus development. Exp Eye Res. 1990 Apr;50(4):339-43. Pubmed: 2338121
  4. Jagannathan NR, Tandon N, Raghunathan P, Kochupillai N: Reversal of abnormalities of myelination by thyroxine therapy in congenital hypothyroidism: localized in vivo proton magnetic resonance spectroscopy (MRS) study. Brain Res Dev Brain Res. 1998 Aug 8;109(2):179-86. Pubmed: 9729372
  5. Kurz W, Wittlinger G, Litmanovitch YI, Romanoff H, Pfeifer Y, Tal E, Sulman FG: Effect of manual lymph drainage massage on urinary excretion of neurohormones and minerals in chronic lymphedema. Angiology. 1978 Oct;29(10):764-72. Pubmed: 717839
  6. Randolph VS: Four clinical chemistry analyses for pediatric patients: glycosylated hemoglobin, free bilirubin, sweat electrolytes, neonatal thyroxine. Am J Med Technol. 1982 Jan;48(1):15-22. Pubmed: 7041647
  7. van Wassenaer AG, Stulp MR, Valianpour F, Tamminga P, Ris Stalpers C, de Randamie JS, van Beusekom C, de Vijlder JJ: The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant. Clin Endocrinol (Oxf). 2002 May;56(5):621-7. Pubmed: 12030913
  8. Etling N, Gehin-Fouque F, Vielh JP, Gautray JP: The iodine content of amniotic fluid and placental transfer of iodinated drugs. Obstet Gynecol. 1979 Mar;53(3):376-80. Pubmed: 424113
  9. Zenovko EI, Pavlov BA, Koreshkov GG, Gudukina GN, Sonkina EG: [Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis] Ter Arkh. 1998;70(1):49-52. Pubmed: 9532653
  10. Hays MT, McGuire RA, Hoogeveen JT, Diezeraad KN: Measurement method for radioactive thyroxine, triiodothyronine, iodide, and iodoprotein in samples with low activity. J Nucl Med. 1980 Mar;21(3):225-32. Pubmed: 7365515
  11. Benvenga S, Alesci S, Trimarchi F: High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry. Thyroid. 2002 Jul;12(7):547-56. Pubmed: 12193297
  12. Hausman GJ, Wright JT, Latimer A, Watson R, Martin RJ: The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus. Obes Res. 1993 Sep;1(5):345-56. Pubmed: 16350585
  13. Gil-Loyzaga P, Remezal M, Mollicone R, Ibanez A, Oriol R: H and B human blood-group antigen expression in cochlear hair cells is modulated by thyroxine. Cell Tissue Res. 1994 May;276(2):239-43. Pubmed: 8020061
  14. Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J: Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 Mar 15;142(6):412-24. Pubmed: 15767619
  15. Bode HH, Vanjonack WJ, Crawford JD: Mitigation of cretinism by breast-feeding. Pediatrics. 1978 Jul;62(1):13-6. Pubmed: 683777
  16. Marks P, Anderson J, Vincent R: Aldosterone in myxoedema. Lancet. 1978 Dec 16;2(8103):1277-8. Pubmed: 82781
  17. Sutherland RL, Simpson-Morgan MW: The thyroxine-binding properties of serum proteins. A competitive binding technique employing sephadex G-25. J Endocrinol. 1975 Jun;65(3):319-32. Pubmed: 807668
  18. Braley-Mullen H, Sharp GC: A thyroxine-containing thyroglobulin peptide induces both lymphocytic and granulomatous forms of experimental autoimmune thyroiditis. J Autoimmun. 1997 Dec;10(6):531-40. Pubmed: 9451592
  19. Raghu P, Reddy GB, Sivakumar B: Inhibition of transthyretin amyloid fibril formation by 2,4-dinitrophenol through tetramer stabilization. Arch Biochem Biophys. 2002 Apr 1;400(1):43-7. Pubmed: 11913969
  20. Hekimsoy Z, Oktem IK: Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res. 2005;31(3):171-5. Pubmed: 16392619

Enzymes

General function:
Involved in calcium ion binding
Specific function:
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Gene Name:
TPO
Uniprot ID:
P07202
Molecular weight:
102961.63
Reactions
3,5-Diiodo-L-tyrosine + Hydrogen peroxide → Thyroxine + 2-Aminoacrylic acid + Waterdetails
General function:
Involved in thyroxine 5'-deiodinase activity
Specific function:
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine). Plays a role in providing a source of plasma T3 by deiodination of T4 in peripheral tissues such as liver and kidney.
Gene Name:
DIO1
Uniprot ID:
P49895
Molecular weight:
28924.21
Reactions
Liothyronine + I(-) + A + Hydrogen Ion → Thyroxine + AH(2)details
General function:
Involved in thyroxine 5'-deiodinase activity
Specific function:
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.
Gene Name:
DIO2
Uniprot ID:
Q92813
Molecular weight:
30551.48
Reactions
Liothyronine + I(-) + A + Hydrogen Ion → Thyroxine + AH(2)details
General function:
Involved in hormone activity
Specific function:
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
Gene Name:
TTR
Uniprot ID:
P02766
Molecular weight:
15886.9
General function:
Involved in serine-type endopeptidase inhibitor activity
Specific function:
Major thyroid hormone transport protein in serum
Gene Name:
SERPINA7
Uniprot ID:
P05543
Molecular weight:
46324.1
General function:
Involved in catalytic activity
Specific function:
Required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier
Gene Name:
SLC3A2
Uniprot ID:
P08195
Molecular weight:
67993.3
General function:
Involved in thyroxine 5'-deiodinase activity
Specific function:
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.
Gene Name:
DIO3
Uniprot ID:
P55073
Molecular weight:
33947.175
Reactions
Liothyronine + I(-) + A + Hydrogen Ion → Thyroxine + AH(2)details
General function:
Not Available
Specific function:
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of thyroxine. Involved in the metabolism of thyroxine (By similarity).
Gene Name:
SULT6B1
Uniprot ID:
Q6IMI4
Molecular weight:
Not Available
Reactions
Phosphoadenosine phosphosulfate + Thyroxine → Adenosine 3',5'-diphosphate + thyroxine-sulfatedetails

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency
Gene Name:
SLCO1C1
Uniprot ID:
Q9NYB5
Molecular weight:
78695.6
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular weight:
76448.0