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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-13 18:15:25 UTC
HMDB IDHMDB00265
Secondary Accession Numbers
  • HMDB06780
Metabolite Identification
Common NameLiothyronine
DescriptionLiothyronine is a T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3. Mildly toxic by ingestion. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx, I(-), and Cl(-). (Sax's Dangerous Properties of Industrial Materials).
Structure
Thumb
Synonyms
  1. 3,3',5'-Triiodo-L-thyronine
  2. 3,3',5'-Triiodothyronine
  3. 3,3',5-Triiodo-L-thyronine
  4. 3,3',5-Triiodothyronine
  5. 3,5,3'-Triiodothyronine
  6. 4-(4-Hydroxy-3-iodophenoxy)-3,5-diiodophenylalanine
  7. Cyronine
  8. L-3,3',5-Triiodo-Thyronine
  9. L-3,3',5-Triiodothyronine
  10. L-3-[4-(4-Hydroxy-3-iodophenoxy)-3,5-diiodophenyl]-Alanine
  11. L-Liothyronine
  12. L-T3
  13. L-Triiodothyronine
  14. Liothyronin
  15. Liothyronine
  16. O-(4-Hydroxy-3-iodophenyl)-3,5-diiodo-L-Tyrosine
  17. T3
  18. Tresitope
  19. Triiodo-L-thyronine
  20. Triiodothyronine
Chemical FormulaC15H12I3NO4
Average Molecular Weight650.9735
Monoisotopic Molecular Weight650.790038137
IUPAC Name(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Traditional IUPAC Nameliothyronine
CAS Registry Number6893-02-3
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC=C(O)C(I)=C2)C(I)=C1)C(O)=O
InChI Identifier
InChI=1S/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1
InChI KeyAUYYCJSJGJYCDS-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
  • Other amino acids(KEGG)
  • Thyroxine(KEGG)
  • amino acid zwitterion(ChEBI)
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 PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility0.019 g/LALOGPS
logP0.82ALOGPS
logP2.8ChemAxon
logS-4.5ALOGPS
pKa (strongest acidic)0.3ChemAxon
pKa (strongest basic)9.48ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area92.78ChemAxon
rotatable bond count5ChemAxon
refractivity113.43ChemAxon
polarizability44.07ChemAxon
Spectra
SpectraMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Gland
  • Epidermis
  • Fibroblasts
  • Intestine
  • Nerve Cells
  • Neuron
  • Placenta
  • Platelet
  • Skeletal Muscle
  • Testes
  • Thyroid Gland
Pathways
NameSMPDB LinkKEGG Link
Tyrosine MetabolismSMP00006map00350
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0029 +/- 0.00019 uMChildren (1-13 years old)BothNormal details
BloodDetected and Quantified0.002 +/- 0.0006 uMAdolescent (13-18 years old)FemaleNormal details
SalivaDetected and Quantified0.0 - 1.0 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0011 +/- 0.00024 uMChildren (1-13 years old)BothMalnutrition (type kwashiorkor and marasmus) details
BloodDetected and Quantified0.0014 +/- 0.0004 uMAdolescent (13-18 years old)FemaleAnorexia nervosa details
UrineDetected and Quantified0.00075 +/- 0.00033 umol/mmol creatinineAdult (>18 years old)BothHyperthyroidism details
UrineDetected and Quantified0.000014 +/- 0.000015 umol/mmol creatinineAdult (>18 years old)BothHypothyroidism 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
Hyperthyroidism
  1. Yoshida K, Sakurada T, Kaise N, Yamamoto M, Kaise K, Saito S, Yoshinaga K: Measurement of triiodothyronine in urine. Tohoku J Exp Med. 1980 Dec;132(4):389-95. Pubmed: 7256725
Hypothyroidism
  1. Yoshida K, Sakurada T, Kaise N, Yamamoto M, Kaise K, Saito S, Yoshinaga K: Measurement of triiodothyronine in urine. Tohoku J Exp Med. 1980 Dec;132(4):389-95. Pubmed: 7256725
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021810
KNApSAcK IDNot Available
Chemspider ID5707
KEGG Compound IDC02465
BioCyc IDLIOTHYRONINE
BiGG ID39878
Wikipedia LinkLiothyronine
NuGOwiki LinkHMDB00265
Metagene LinkHMDB00265
METLIN ID5265
PubChem Compound5920
PDB IDT3
ChEBI ID18258
References
Synthesis ReferenceSalamonczyk, Grzegorz M.; Oza, Vibha B.; Sih, Charles J. A concise synthesis of thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3). Tetrahedron Letters (1997), 38(40), 6965-69
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE: Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005 Jul;77(1):41-53. Epub 2005 May 11. Pubmed: 15889350
  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. 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
  4. Stalenheim EG: Long-term validity of biological markers of psychopathy and criminal recidivism: follow-up 6-8 years after forensic psychiatric investigation. Psychiatry Res. 2004 Jan 1;121(3):281-91. Pubmed: 14675747
  5. Zimmermann-Belsing T, Dreyer M, Holst JJ, Feldt-Rasmussen U: The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects. Clin Endocrinol (Oxf). 1998 Nov;49(5):589-95. Pubmed: 10197073
  6. Holt PJ: In vitro responses of the epidermis to triiodothyronine. J Invest Dermatol. 1978 Sep;71(3):202-4. Pubmed: 690484
  7. Mizuma H, Murakami M, Mori M: Thyroid hormone activation in human vascular smooth muscle cells: expression of type II iodothyronine deiodinase. Circ Res. 2001 Feb 16;88(3):313-8. Pubmed: 11179199
  8. Himms-Hagen J: Brown adipose tissue thermogenesis: interdisciplinary studies. FASEB J. 1990 Aug;4(11):2890-8. Pubmed: 2199286
  9. Gledhill RF, Dessein PH, Van der Merwe CA: Treatment of Raynaud's phenomenon with triiodothyronine corrects co-existent autonomic dysfunction: preliminary findings. Postgrad Med J. 1992 Apr;68(798):263-7. Pubmed: 1409189
  10. Kassem M, Brixen K, Mosekilde L, Blum WF, Flyvbjerg A: Effects of growth hormone treatment on serum levels of insulin-like growth factors (IGFs) and IGF binding proteins 1-4 in postmenopausal women. Clin Endocrinol (Oxf). 1998 Dec;49(6):747-56. Pubmed: 10209562
  11. Llewellyn L, Ramsurn VP, Wigham T, Sweeney GE, Power DM: Cloning, characterisation and expression of the apolipoprotein A-I gene in the sea bream (Sparus aurata). Biochim Biophys Acta. 1998 Nov 8;1442(2-3):399-404. Pubmed: 9804999
  12. Dutkiewicz S, Witeska A, Nauman A: The deiodination of thyroxine to triiodothyronine in the testes of patients with prostate cancer. Int Urol Nephrol. 1995;27(1):81-5. Pubmed: 7615374
  13. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S, Gallagher D, Mayer L, Murphy E, Leibel RL: Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest. 2005 Dec;115(12):3579-86. Pubmed: 16322796
  14. Urcelay E, Jareno MA, Menaya J, Parrilla R, Ayuso MS, Martin-Requero A: Cloning and functional characterization of the 5' regulatory region of the human mitochondrial glycerol-3-phosphate dehydrogenase gene. Lack of 3,5,3'-triiodothyronine responsiveness in adipose tissue. Eur J Biochem. 2000 Dec;267(24):7209-17. Pubmed: 11106433
  15. Lebon V, Dufour S, Petersen KF, Ren J, Jucker BM, Slezak LA, Cline GW, Rothman DL, Shulman GI: Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. J Clin Invest. 2001 Sep;108(5):733-7. Pubmed: 11544279
  16. Iwao H, Abe Y: [Expression of the renin and angiotensinogen genes] Nippon Yakurigaku Zasshi. 1991 Jan;97(1):1-11. Pubmed: 2045011
  17. Calvo R, Obregon MJ, Ruiz de Ona C, Escobar del Rey F, Morreale de Escobar G: Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain. J Clin Invest. 1990 Sep;86(3):889-99. Pubmed: 2394838
  18. Haas MJ, Fishman M, Mreyoud A, Mooradian AD: Thyroid hormone responsive protein (THRP) mediates thyroid hormone-induced cytotoxicity in primary neuronal cultures. Exp Brain Res. 2005 Jan;160(4):424-32. Epub 2004 Oct 15. Pubmed: 15490139

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
Iodotyrosine + 3,5-Diiodo-L-tyrosine + Hydrogen peroxide → Liothyronine + 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 transport
Specific function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc
Gene Name:
ALB
Uniprot ID:
P02768
Molecular weight:
69365.9
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 sequence-specific DNA binding transcription factor activity
Specific function:
High affinity receptor for triiodothyronine
Gene Name:
THRB
Uniprot ID:
P10828
Molecular weight:
52787.2
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:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Nuclear hormone receptor. High affinity receptor for triiodothyronine
Gene Name:
THRA
Uniprot ID:
P10827
Molecular weight:
54815.1