Human Metabolome Database Version 3.5

Showing metabocard for Thyroxine (HMDB00248)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:08:10 -0700
HMDB ID HMDB00248
Secondary Accession Numbers
  • HMDB01918
Metabolite Identification
Common Name Thyroxine
Description The 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
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C15H11I4NO4
Average Molecular Weight 776.87
Monoisotopic Molecular Weight 776.686681525
IUPAC Name (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Traditional IUPAC Name levothyroxine
CAS Registry Number 51-48-9
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 Key XUIIKFGFIJCVMT-LBPRGKRZSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Amino Acids, Peptides, and Analogues
Class Amino Acids and Derivatives
Sub Class Alpha 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 Parent Alpha Amino Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
Application Not Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 235.5 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.009 g/L ALOGPS
LogP 1.15 ALOGPS
LogP 3.73 ChemAxon
LogS -4.94 ALOGPS
pKa (strongest acidic) 0.27 ChemAxon
pKa (strongest basic) 9.43 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 3 ChemAxon
Polar Surface Area 92.78 A2 ChemAxon
Rotatable Bond Count 5 ChemAxon
Refractivity 126.79 ChemAxon
Polarizability 49.52 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Muscle
  • Skeletal Muscle
  • Fibroblasts
  • Intestine
  • Neuron
  • Placenta
  • Testes
  • Thyroid Gland
  • Myelin
  • Prostate
  • Adipose Tissue
  • Nerve Cells
  • Platelet
  • Gonads
  • Spleen
Pathways
Name SMPDB Link KEGG Link
Tyrosine Metabolism SMP00006 map00350 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.000009 - 0.000023 uM Not Available Both Comment Normal
  • Geigy Scient...
Blood Detected and Quantified
0.12 +/- 0.0061 uM Children (1-13 year old) Both Normal
Blood Detected and Quantified
0.000016 (0.0000064-0.000064) uM Adult (>18 years old) Both Normal
Blood Detected and Quantified
0.0000144 +/- 0.0000036 uM Adolescent (13-18 years old) Female Normal
Blood Detected and Quantified
0.00002 (0.00001-0.00003) uM Adult (>18 years old) Both Normal
  • Wu AHB. Tiet...
Saliva Detected and Quantified
0.0 - 1.0 uM Adult (>18 years old) Both Normal
Urine Detected and Quantified
0.00032 +/- 0.00015 umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 0.0000185 +/- 0.0000052 uM Adult (>18 years old) Both Hypothyroidism
Blood Detected and Quantified 0.057 +/- 0.0058 uM Children (1-13 year old) Both Severely malnourished children
Blood Detected and Quantified 0.000011 +/- 0.0000016 uM Adolescent (13-18 years old) Female Anorexia nervosa
Urine Detected and Quantified 0.0015 +/- 0.00154 umol/mmol creatinine Adult (>18 years old) Both Proteinuria
Associated Disorders and Diseases
Disease References
Anorexia nervosa
  • 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 Link_out
      Hypothyroidism
      • 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 Link_out
          Proteinuria
          • 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 Link_out
              Associated OMIM IDs
              DrugBank ID Not Available
              DrugBank Metabolite ID Not Available
              Phenol Explorer Compound ID Not Available
              Phenol Explorer Metabolite ID Not Available
              FoodDB ID FDB021829
              KNApSAcK ID Not Available
              Chemspider ID 5614 Link_out
              KEGG Compound ID C01829 Link_out
              BioCyc ID L-THYROXINE Link_out
              BiGG ID 38499 Link_out
              Wikipedia Link Thyroxine Link_out
              NuGOwiki Link HMDB00248 Link_out
              Metagene Link HMDB00248 Link_out
              METLIN ID 439 Link_out
              PubChem Compound 5819 Link_out
              PDB ID T44 Link_out
              ChEBI ID 18332 Link_out
              References
              Synthesis Reference Martinovich, 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. 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 Link_out
              2. 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 Link_out
              3. 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 Link_out
              4. 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 Link_out
              5. 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 Link_out
              6. 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 Link_out
              7. 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 Link_out
              8. 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 Link_out
              9. 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 Link_out
              10. 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 Link_out
              11. 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 Link_out
              12. 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 Link_out
              13. 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 Link_out
              14. Bode HH, Vanjonack WJ, Crawford JD: Mitigation of cretinism by breast-feeding. Pediatrics. 1978 Jul;62(1):13-6. Pubmed: 683777 Link_out
              15. Marks P, Anderson J, Vincent R: Aldosterone in myxoedema. Lancet. 1978 Dec 16;2(8103):1277-8. Pubmed: 82781 Link_out
              16. 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 Link_out
              17. 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 Link_out
              18. 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 Link_out
              19. Hekimsoy Z, Oktem IK: Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res. 2005;31(3):171-5. Pubmed: 16392619 Link_out
              20. 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 Link_out

              Enzymes
              Name: Thyroid peroxidase
              Reactions:
              3,5-Diiodo-L-tyrosine + Hydrogen peroxide unknown Thyroxine + 2-Aminoacrylic acid + Water details
              Gene Name: TPO
              Uniprot ID: P07202 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Type I iodothyronine deiodinase
              Reactions:
              Liothyronine + I(-) + A + Hydrogen Ion unknown Thyroxine + AH(2) details
              Gene Name: DIO1
              Uniprot ID: P49895 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Type II iodothyronine deiodinase
              Reactions:
              Liothyronine + I(-) + A + Hydrogen Ion unknown Thyroxine + AH(2) details
              Gene Name: DIO2
              Uniprot ID: Q92813 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Transthyretin
              Reactions: Not Available
              Gene Name: TTR
              Uniprot ID: P02766 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Thyroxine-binding globulin
              Reactions: Not Available
              Gene Name: SERPINA7
              Uniprot ID: P05543 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: 4F2 cell-surface antigen heavy chain
              Reactions: Not Available
              Gene Name: SLC3A2
              Uniprot ID: P08195 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Type III iodothyronine deiodinase
              Reactions:
              Liothyronine + I(-) + A + Hydrogen Ion unknown Thyroxine + AH(2) details
              Gene Name: DIO3
              Uniprot ID: P55073 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Sulfotransferase 6B1
              Reactions:
              Phosphoadenosine phosphosulfate + Thyroxine unknown Adenosine 3',5'-diphosphate + thyroxine-sulfate details
              Gene Name: SULT6B1
              Uniprot ID: Q6IMI4 Link_out
              Transporters
              Name: Solute carrier organic anion transporter family member 1C1
              Reactions: Not Available
              Gene Name: SLCO1C1
              Uniprot ID: Q9NYB5 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Solute carrier organic anion transporter family member 1B1
              Reactions: Not Available
              Gene Name: SLCO1B1
              Uniprot ID: Q9Y6L6 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA