You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-14 15:39:04 UTC
HMDB IDHMDB0000335
Secondary Accession Numbers
  • HMDB00335
Metabolite Identification
Common Name16a-Hydroxyestrone
Description16a-Hydroxyestrone or 16alpha-hydroxyestrone (16α-OH-E1 or 16a OHE1), or hydroxyestrone, is an endogenous steroidal estrogen and a major metabolite of estrone and estradiol. 16a-hydroxyestrone belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane. Thus, 16a-hydroxyestrone is considered to be a steroid molecule. 16a-hydroxyestrone is found in all vertebrates. Vertebrates, especially mammals, metabolizes estrogen into two major pathways and one minor. The two major pathways lead to 2-hydroxyestrone and 16a-hydroxyestrone (2-OHE1 and 16a OHE1 respectively). The minor pathway leads to 4-hydroxyestrone (4-OHE1). 2a-hydroxyestrone is considered to be the good metabolite (PMID: 8943806 ) as 2-hydroxyestrone does not stimulate cell growth and it blocks the action of stronger estrogens that may be carcinogenic. 16a-Hydroxyestrone, on the other hand, has a significantly stronger estrogenic activity, and studies show that it may increase the risk of breast cancer. The binding of 16a-hydroxyestrone to the estrogen receptor is reported to be covalent and irreversible (PMID: 3186693 ). A low urinary ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone is a strong predictor of breast cancer risk among women (PMID: 19502596 ).
Structure
Data?1582752124
Synonyms
ValueSource
16 alpha OHEChEBI
3,16alpha-Dihydroxy-1,3,5(10)-estratrien-17-oneChEBI
3,16alpha-Dihydroxyestra-1,3,5(10)-trien-17-oneChEBI
Estra-1,3,5(10)-triene-3,16alpha-diol-17-oneChEBI
16 a OHEGenerator
16 Α oheGenerator
3,16a-Dihydroxy-1,3,5(10)-estratrien-17-oneGenerator
3,16Α-dihydroxy-1,3,5(10)-estratrien-17-oneGenerator
3,16a-Dihydroxyestra-1,3,5(10)-trien-17-oneGenerator
3,16Α-dihydroxyestra-1,3,5(10)-trien-17-oneGenerator
Estra-1,3,5(10)-triene-3,16a-diol-17-oneGenerator
Estra-1,3,5(10)-triene-3,16α-diol-17-oneGenerator
16 alpha-HydroxyestroneHMDB
3,16a-Dihydroxy-estra-1,3,5(10)-trien-17-oneHMDB
16 beta-HydroxyestroneHMDB
16-alpha-HydroxyestroneHMDB
16-HydroxyestroneHMDB
Chemical FormulaC18H22O3
Average Molecular Weight286.3655
Monoisotopic Molecular Weight286.15689457
IUPAC Name(1S,10R,11S,13R,15S)-5,13-dihydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-one
Traditional Name(1S,10R,11S,13R,15S)-5,13-dihydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-one
CAS Registry Number566-76-7
SMILES
[H][C@@]12C[C@@H](O)C(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
InChI Identifier
InChI=1S/C18H22O3/c1-18-7-6-13-12-5-3-11(19)8-10(12)2-4-14(13)15(18)9-16(20)17(18)21/h3,5,8,13-16,19-20H,2,4,6-7,9H2,1H3/t13-,14-,15+,16-,18+/m1/s1
InChI KeyWPOCIZJTELRQMF-QFXBJFAPSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 3-hydroxysteroid
  • Hydroxysteroid
  • 17-oxosteroid
  • Oxosteroid
  • 16-alpha-hydroxysteroid
  • 16-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Carbonyl group
  • Organooxygen compound
  • Alcohol
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.047 g/LALOGPS
logP2.45ALOGPS
logP3.44ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity80.57 m³·mol⁻¹ChemAxon
Polarizability32.06 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Collision Cross Sections

NameAdductTypeData SourceValueReference
DarkChem[M+H]+PredictedNot Available168.01931661259
DarkChem[M-H]-PredictedNot Available166.00431661259
AllCCS[M+H]+PredictedNot Available170.51232859911
AllCCS[M-H]-PredictedNot Available175.49532859911

Retention Indices

Underivatized

Not Available

Derivatized

DerivativeValueReference
16a-Hydroxyestrone,1TMS,#12768.0334https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,1TMS,#22786.1277https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,1TMS,#32768.1338https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TMS,#12875.1064https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TMS,#22779.4495https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TMS,#32838.9927https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,1TBDMS,#13049.548https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,1TBDMS,#23088.4634https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,1TBDMS,#33043.648https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TBDMS,#13412.7769https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TBDMS,#23287.0981https://arxiv.org/abs/1905.12712
16a-Hydroxyestrone,2TBDMS,#33331.4954https://arxiv.org/abs/1905.12712
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-0019-3941100000-3a930f8cc95b733c86532014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-0019-3941100000-3e52ec60bd9142c09b742014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0019-3941100000-3a930f8cc95b733c86532017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0019-3941100000-3e52ec60bd9142c09b742017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ab9-2690000000-4da4066a9998d4bb71522017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0gj1-1193300000-a36ac7539d25b407ca9f2017-10-06View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0090000000-ea49b0e7c1a26f8807b32017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ap0-0490000000-7a9632ca2f7369b28ad32017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0gb9-7980000000-f674402195ec376faeb72017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-91f32a5e866ea149a4a42017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0090000000-f8524ff8a5fae66251ad2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-02dl-1090000000-5ac386a35fc2bb3cc1f02017-09-01View Spectrum

NMR

Spectrum TypeDescriptionDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, 100%_DMSO, experimental)2012-12-04View Spectrum
2D NMR[1H, 13C] NMR Spectrum (2D, 600 MHz, 100%_DMSO, predicted)2012-12-05View Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00078 (0.00076-0.00081) uMAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000817 (0.0008-0.00084) uMAdult (>18 years old)FemaleBreast cancer details
Associated Disorders and Diseases
Disease References
Perillyl alcohol administration for cancer treatment
  1. Cauley JA, Zmuda JM, Danielson ME, Ljung BM, Bauer DC, Cummings SR, Kuller LH: Estrogen metabolites and the risk of breast cancer in older women. Epidemiology. 2003 Nov;14(6):740-4. [PubMed:14569192 ]
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB021959
KNApSAcK IDNot Available
Chemspider ID103012
KEGG Compound IDC05300
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID2580
PubChem Compound115116
PDB IDNot Available
ChEBI ID776
Food Biomarker OntologyNot Available
VMH IDC05300
MarkerDB IDNot Available
References
Synthesis ReferenceKnuppen, R.; Breuer, H. Biogenesis of 11b-hydroxyestrone and 16a-hydroxyestrone by adrenal tissue. Biochimica et Biophysica Acta (1962), 58 147-8.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Bradlow HL, Telang NT, Sepkovic DW, Osborne MP: 2-hydroxyestrone: the 'good' estrogen. J Endocrinol. 1996 Sep;150 Suppl:S259-65. [PubMed:8943806 ]
  2. Swaneck GE, Fishman J: Covalent binding of the endogenous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7831-5. doi: 10.1073/pnas.85.21.7831. [PubMed:3186693 ]
  3. Im A, Vogel VG, Ahrendt G, Lloyd S, Ragin C, Garte S, Taioli E: Urinary estrogen metabolites in women at high risk for breast cancer. Carcinogenesis. 2009 Sep;30(9):1532-5. doi: 10.1093/carcin/bgp139. Epub 2009 Jun 5. [PubMed:19502596 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Capable of catalyzing the interconversion of testosterone and androstenedione, as well as estradiol and estrone. Also has 20-alpha-HSD activity. Uses NADH while EDH17B3 uses NADPH.
Gene Name:
HSD17B2
Uniprot ID:
P37059
Molecular weight:
42784.75
General function:
Involved in oxidoreductase activity
Specific function:
NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. Has very low activity towards testosterone. The heteroteramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria.
Gene Name:
HSD17B8
Uniprot ID:
Q92506
Molecular weight:
26973.56
General function:
Involved in estradiol 17-beta-dehydrogenase activity
Specific function:
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Gene Name:
HSD17B1
Uniprot ID:
P14061
Molecular weight:
34949.715
General function:
Involved in oxidoreductase activity
Specific function:
Responsible for the reduction of the keto group on the C-3 of sterols.
Gene Name:
HSD17B7
Uniprot ID:
P56937
Molecular weight:
38205.77