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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-14 15:20:01 UTC
HMDB IDHMDB0000248
Secondary Accession Numbers
  • HMDB0001918
  • HMDB00248
  • HMDB01918
Metabolite Identification
Common NameThyroxine
DescriptionThyroxine (3,5,3′,5′-tetraiodothyronine) or T4 is one of two major hormones derived from the thyroid gland, the other being triiodothyronine (T3). The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. In humans, the ratio of T4 to T3 released into the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by enzymes known as deiodinases (5′-iodinase). Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Iodine is critical to the synthesis of thyroxine and other thyroid hormones. Through a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues found in the thyroglobulin protein, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). Linking two moieties of DIT produces thyroxine. Combining one molecule of MIT and one molecule of DIT produces triiodothyronine. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles where thyroxine is produced. If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in a condition called goitre. More specifically, the lack of thyroid hormones will lead to decreased negative feedback on the pituitary gland, leading to increased production of thyroid-stimulating hormone, which causes the thyroid to enlarge, leading to goitre. Thyroxine can be peripherally de-iodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. They act on nearly every cell in the body. In particular, thyroid hormones act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. Levothyroxine, a manufactured form of thyroxine, was the most prescribed medication in the United States with more than 114 million prescriptions.
Structure
Data?1582752118
Synonyms
ValueSource
3,3',5,5'-Tetraiodo-L-thyronineChEBI
3,5,3',5'-TETRAIODO-L-thyronineChEBI
4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodo-L-phenylalanineChEBI
L-T4ChEBI
LevothyroxinChEBI
LevothyroxineChEBI
LT4ChEBI
O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosineChEBI
T4ChEBI
L-ThyroxineKegg
O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosineKegg
3,5,3'5'-Tetraiodo-L-thyronineKegg
ForthyronKegg
(-)-ThyroxineHMDB
3,3',5,5''-tetraiodo-L-ThyronineHMDB
3,5,3',5'-TetraiodothyronineHMDB, MeSH
D-ThyroxineHMDB
DL-ThyroxinHMDB
HenningHMDB
L-3,5,3',5'-TetraiodothyronineHMDB, MeSH
L-ThyroxinHMDB
LaevothyroxinumHMDB
LevothroidHMDB, MeSH
Levothyroxine sodiumHMDB, MeSH
LevothyroxinumHMDB
LevoxylHMDB, MeSH
Prestwick_548HMDB
SynthroidHMDB, MeSH
TetraiodothyronineHMDB
TetrametHMDB
THXHMDB
ThyratabsHMDB
ThyraxHMDB, MeSH
ThyreoideumHMDB
ThyroxinHMDB, MeSH
ThyroxinalHMDB
Thyroxine I 125HMDB
Thyroxine iodineHMDB
Allphar brand OF levothyroxine sodiumMeSH, HMDB
BerlthyroxMeSH, HMDB
Delalande, levothyroxinMeSH, HMDB
DexnonMeSH, HMDB
EferoxMeSH, HMDB
EltroxinMeSH, HMDB
Kern brand OF levothyroxine sodiumMeSH, HMDB
L-ThyroxMeSH, HMDB
L-Thyroxin henningMeSH, HMDB
L-Thyroxin betaMeSH, HMDB
L-Thyroxine rocheMeSH, HMDB
Levothyroxin deladandeMeSH, HMDB
LévothyroxMeSH, HMDB
Merck lipha santé brand OF levothyroxine sodiumMeSH, HMDB
Nourypharma brand OF levothyroxine sodiumMeSH, HMDB
OroxineMeSH, HMDB
Aventis brand OF levothyroxine sodiumMeSH, HMDB
EuthyroxMeSH, HMDB
EutiroxMeSH, HMDB
Forest brand OF levothyroxine sodiumMeSH, HMDB
Genpharm brand OF levothyroxine sodiumMeSH, HMDB
GlaxoSmithKline brand OF levothyroxine sodiumMeSH, HMDB
Goldshield brand OF levothyroxine sodiumMeSH, HMDB
LThyroxin henningMeSH, HMDB
levo-TMeSH, HMDB
Sanofi synthelabo brand OF levothyroxine sodiumMeSH, HMDB
Sigma brand OF levothyroxine sodiumMeSH, HMDB
SynthroxMeSH, HMDB
ThevierMeSH, HMDB
Watson brand OF levothyroxine sodiumMeSH, HMDB
Berlin chemie brand OF levothyroxine sodiumMeSH, HMDB
Delalande brand OF levothyroxine sodiumMeSH, HMDB
EltroxineMeSH, HMDB
Hexal brand 2 OF levothyroxine sodiumMeSH, HMDB
L Thyroxine rocheMeSH, HMDB
NovothyralMeSH, HMDB
TiroidineMeSH, HMDB
Vortex brand OF levothyroxine sodiumMeSH, HMDB
Abbot brand OF levothyroxine sodiumMeSH, HMDB
Berlin-chemie brand OF levothyroxine sodiumMeSH, HMDB
Byk brand OF levothyroxine sodiumMeSH, HMDB
Deladande, levothyroxinMeSH, HMDB
GlaxoWellcome brand OF levothyroxine sodiumMeSH, HMDB
Henning berlin brand OF levothyroxine sodiumMeSH, HMDB
Hexal brand 1 OF levothyroxine sodiumMeSH, HMDB
L ThyroxMeSH, HMDB
L Thyroxin henningMeSH, HMDB
L Thyroxin betaMeSH, HMDB
L ThyroxineMeSH, HMDB
LThyroxin betaMeSH, HMDB
leo, TiroxinaMeSH, HMDB
levo TMeSH, HMDB
LevoTMeSH, HMDB
LevothyroidMeSH, HMDB
Levothyroxin delalandeMeSH, HMDB
LevoxineMeSH, HMDB
Merck brand OF levothyroxine sodiumMeSH, HMDB
Monarch brand OF levothyroxine sodiumMeSH, HMDB
Mova brand OF levothyroxine sodiumMeSH, HMDB
NovothyroxMeSH, HMDB
O-(4-Hydroxy-3,5-diiodophenyl) 3,5-diiodo-L-tyrosineMeSH, HMDB
O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodotyrosineMeSH, HMDB
Roche brand OF levothyroxine sodiumMeSH, HMDB
Rudefsa brand OF levothyroxine sodiumMeSH, HMDB
Sodium levothyroxineMeSH, HMDB
T4 Thyroid hormoneMeSH, HMDB
Thyroid hormone, T4MeSH, HMDB
Tiroxina leoMeSH, HMDB
UnithroidMeSH, HMDB
Betapharm brand OF levothyroxine sodiumMeSH, HMDB
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
Description Belongs to the class of organic compounds known as phenylalanine and derivatives. Phenylalanine and derivatives are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPhenylalanine and derivatives
Alternative Parents
Substituents
  • Phenylalanine or derivatives
  • Diphenylether
  • Diaryl ether
  • 3-phenylpropanoic-acid
  • Alpha-amino acid
  • Amphetamine or derivatives
  • L-alpha-amino acid
  • Phenoxy compound
  • Phenol ether
  • 2-halophenol
  • 2-iodophenol
  • Aralkylamine
  • Phenol
  • Halobenzene
  • Iodobenzene
  • Aryl halide
  • Aryl iodide
  • Benzenoid
  • Monocyclic benzene moiety
  • Amino acid
  • Carboxylic acid
  • Ether
  • Monocarboxylic acid or derivatives
  • Organoiodide
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxide
  • Carbonyl group
  • Primary amine
  • Amine
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Organic oxygen compound
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Biological locationSource
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point235.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M-H]-Not Available206.155http://allccs.zhulab.cn/database/detail?ID=AllCCS00000013
Predicted Molecular 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 Area92.78 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.79 m³·mol⁻¹ChemAxon
Polarizability49.4 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
AllCCS[M+H]+207.05432859911
AllCCS[M-H]-212.65632859911
DeepCCS[M+H]+216.19830932474
DeepCCS[M-H]-213.66330932474
DeepCCS[M-2H]-247.95530932474
DeepCCS[M+Na]+223.30830932474
AllCCS[M+H]+207.132859911
AllCCS[M+H-H2O]+206.332859911
AllCCS[M+NH4]+207.732859911
AllCCS[M+Na]+207.932859911
AllCCS[M-H]-212.732859911
AllCCS[M+Na-2H]-214.932859911
AllCCS[M+HCOO]-217.632859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
ThyroxineN[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O4887.2Standard polar33892256
ThyroxineN[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O3942.7Standard non polar33892256
ThyroxineN[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O4159.2Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0f89-4002002900-0d489fed1cb888a2d9d02017-11-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Thyroxine GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-10-18Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine Quattro_QQQ 10V, Positive-QTOF (Annotated)splash10-0ac9-0591664310-c9b7aec3184ebb20a2da2012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine Quattro_QQQ 25V, Positive-QTOF (Annotated)splash10-014i-2566449540-35bb942c7bcbcfe41af72012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine Quattro_QQQ 40V, Positive-QTOF (Annotated)splash10-00xr-3375497520-9dee3cb0c153e6c6df9e2012-07-24HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine , positive-QTOFsplash10-0059-0001001900-83ff4aafed0b73c6c7b72017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 35V, Negative-QTOFsplash10-004i-0900000000-6e0a640216afcce0837e2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 45V, Negative-QTOFsplash10-004i-0900000000-9223d3d63e3db43052a72021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 60V, Negative-QTOFsplash10-004i-0900000000-1e8e674422aa4d820da72021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 20V, Positive-QTOFsplash10-001i-0132219000-42259b5a596f74aec76f2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 40V, Positive-QTOFsplash10-0udi-0019217000-baafc92556cb18d71b3a2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 30V, Negative-QTOFsplash10-004i-0900000000-bb154453510a75ca822c2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 15V, Negative-QTOFsplash10-004i-0900000000-f785346765de92765afd2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 20V, Positive-QTOFsplash10-001i-0000119000-af7b1e923ec5750514af2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 10V, Positive-QTOFsplash10-0f8j-1248309000-68eea5695ceb400ea5b02021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 40V, Positive-QTOFsplash10-0udi-0029337000-a85b59c3575dc95d36fd2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Thyroxine 10V, Positive-QTOFsplash10-001i-0003109000-480d647f8d49feeec28c2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 10V, Positive-QTOFsplash10-01si-0000000900-524d052a32c1fe4b904d2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 20V, Positive-QTOFsplash10-001i-0000001900-553f6a4045ef2241fd852017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 40V, Positive-QTOFsplash10-014i-0009000000-d2431d885a79bb80b7a52017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 10V, Negative-QTOFsplash10-004i-0000000900-137b5f8f48031bc9aa4f2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 20V, Negative-QTOFsplash10-03fr-0004001900-db1d8cdb93785d7863822017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 40V, Negative-QTOFsplash10-0h9u-7029014300-3bd9620b0c6a8dd20c932017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 10V, Negative-QTOFsplash10-004i-0000000900-95266ab7e52b7d3cb3222021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 20V, Negative-QTOFsplash10-004i-1700000900-195c16ab7434b857e7122021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 40V, Negative-QTOFsplash10-004i-0900000000-0dba40d354fa6a5575e02021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Thyroxine 10V, Positive-QTOFsplash10-004i-0000000900-d76aec17d3d890cb64c12021-09-25Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Experimental 1D NMR1H NMR Spectrum (1D, 600 MHz, 100%_DMSO, experimental)2012-12-04Wishart LabView Spectrum
Experimental 2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, 100%_DMSO, experimental)2012-12-05Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Saliva
  • Urine
Tissue Locations
  • Adipose Tissue
  • Fibroblasts
  • Intestine
  • Neuron
  • Ovary
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testis
  • Thyroid Gland
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000009 - 0.000023 uMNot AvailableBoth
Normal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.13 +/- 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 Quantified0.0600-0.150 uMChildren (1-13 years old)Not Specified
Normal
details
BloodDetected and Quantified0.105-0.215 uMNewborn (0-30 days old)BothNormal details
BloodDetected and Quantified0.0700-0.175 uMInfant (0-1 year old)BothNormal details
BloodDetected and Quantified60-160 uMChildren (1-13 years old)Not Specified
Normal
details
BloodDetected and Quantified0.000010 - 0.000023 uMAdult (>18 years old)Female
Normal
details
BloodDetected and Quantified0.000010 - 0.000023 uMAdult (>18 years old)Male
Normal
details
BloodDetected and Quantified0.000010 - 0.000023 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.0399 - 0.162 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.000012-0.000025 uMAdult (>18 years old)Not Specified
Normal
details
BloodDetected and Quantified0.00001-0.000023 uMChildren (1-13 years old)Not Specified
Normal
details
BloodDetected and Quantified0.000009-0.00002 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified0.0579-0.148 uMChildren (1-13 years old)Not SpecifiedNormal details
BloodDetected and Quantified0.0515-0.142 uMInfant (0-1 year old)Not SpecifiedNormal 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
BiospecimenStatusValueAgeSexConditionReferenceDetails
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
BloodDetected and Quantified<0.0100 uMChildren (1-13 years old)Male
Pituitary Hormone Deficiency, Combined, 1
details
BloodDetected and Quantified0.0540-0.112 uMNewborn (0-30 days old)BothPendred Syndrome details
BloodDetected and Quantified0.0260-0.164 uMInfant (0-1 year old)MalePendred Syndrome details
BloodDetected and Quantified0.0953 uMAdult (>18 years old)Female
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified23-55.2 uMChildren (1-13 years old)Both
Hypothyroidism, congenital, nongoitrous, 2
details
BloodDetected and Quantified0.000009 uMChildren (1-13 years old)Female
Pituitary Hormone Deficiency, Combined, 1
details
BloodDetected and Quantified0.00000219 uMAdult (>18 years old)Male
Pituitary Hormone Deficiency, Combined, 1
details
BloodDetected and Quantified0.00000557 uMChildren (1-13 years old)Male
Pituitary Hormone Deficiency, Combined, 1
details
BloodDetected and Quantified0.000009 uMAdult (>18 years old)FemaleProprotein Convertase 1/3 Deficiency details
BloodDetected and Quantified0.0180-0.0206 uMChildren (1-13 years old)Male
Hypothyroidism, congenital, nongoitrous, 2
details
BloodDetected and Quantified0.0579 uMNewborn (0-30 days old)MaleDiabetes Mellitus, Congenital Insulin-dependent, With Fatal Secretory Diarrhea; Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-linked, Formerly details
BloodDetected and Quantified0.0747 uMInfant (0-1 year old)FemaleLeptin Deficiency or Dysfunction 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 ]
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
  1. Hattori N, Ishihara T, Moridera K, Hino M, Ikekubo K, Kurahachi H: A case of late-onset congenital adrenal hyperplasia due to partial 3 beta-hydroxysteroid dehydrogenase deficiency. Endocr J. 1993 Feb;40(1):107-9. [PubMed:7951484 ]
Pituitary Hormone Deficiency, Combined, 1
  1. Bertko E, Klammt J, Dusatkova P, Bahceci M, Gonc N, Ten Have L, Kandemir N, Mansmann G, Obermannova B, Oostdijk W, Pfaffle H, Rockstroh-Lippold D, Schlicke M, Tuzcu AK, Pfaffle R: Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes. J Hum Genet. 2017 Aug;62(8):755-762. doi: 10.1038/jhg.2017.34. Epub 2017 Mar 30. [PubMed:28356564 ]
  2. Ayoola OO, Oladejo FA, Dattani M, Clayton PE: Multiple pituitary hormone deficiency caused by pit-I mutation and the challenges of management in a developing country. Ann Ib Postgrad Med. 2008 Dec;6(2):21-6. [PubMed:25161449 ]
Pendred Syndrome
  1. Coakley JC, Keir EH, Connelly JF: The association of thyroid dyshormonogenesis and deafness (Pendred syndrome): experience of the Victorian Neonatal Thyroid Screening Programme. J Paediatr Child Health. 1992 Oct;28(5):398-401. [PubMed:1389454 ]
Proprotein Convertase 1/3 Deficiency
  1. O'Rahilly S, Gray H, Humphreys PJ, Krook A, Polonsky KS, White A, Gibson S, Taylor K, Carr C: Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med. 1995 Nov 23;333(21):1386-90. doi: 10.1056/NEJM199511233332104. [PubMed:7477119 ]
Hypothyroidism, congenital, nongoitrous, 2
  1. White CW, Wiedermann BL, Kirkland RT, Clayton GW: Hereditary congenital nongoitrous hypothyroidism. Am J Dis Child. 1981 Jun;135(6):568-9. [PubMed:7234795 ]
  2. Al Taji E, Biebermann H, Limanova Z, Hnikova O, Zikmund J, Dame C, Gruters A, Lebl J, Krude H: Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism. Eur J Endocrinol. 2007 May;156(5):521-9. doi: 10.1530/EJE-06-0709. [PubMed:17468187 ]
Diabetes Mellitus, Congenital Insulin-dependent, With Fatal Secretory Diarrhea; Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-linked, Formerly
  1. Levy-Lahad E, Wildin RS: Neonatal diabetes mellitus, enteropathy, thrombocytopenia, and endocrinopathy: Further evidence for an X-linked lethal syndrome. J Pediatr. 2001 Apr;138(4):577-80. doi: 10.1067/mpd.2001.111502. [PubMed:11295725 ]
Leptin Deficiency or Dysfunction
  1. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999 Sep 16;341(12):879-84. doi: 10.1056/NEJM199909163411204. [PubMed:10486419 ]
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
  • 606788 (Anorexia nervosa)
  • 201810 (Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency)
  • 613038 (Pituitary Hormone Deficiency, Combined, 1)
  • 274600 (Pendred Syndrome)
  • 600955 (Proprotein Convertase 1/3 Deficiency)
  • 218700 (Hypothyroidism, congenital, nongoitrous, 2)
  • 304790 (Diabetes Mellitus, Congenital Insulin-dependent, With Fatal Secretory Diarrhea; Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-linked, Formerly)
  • 614962 (Leptin Deficiency or Dysfunction)
DrugBank IDDB00451
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5614
KEGG Compound IDC01829
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevothyroxine
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID18332
Food Biomarker OntologyNot Available
VMH IDTHYOX_L
MarkerDB IDMDB00000121
Good Scents IDNot Available
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. doi: 10.1038/nature07762. [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