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Record Information
Version3.6
Creation Date2006-08-13 10:11:15 UTC
Update Date2016-02-11 01:06:33 UTC
HMDB IDHMDB04063
Secondary Accession NumbersNone
Metabolite Identification
Common NameMetanephrine
DescriptionMetanephrine is a metabolite of epinephrine created by action of catechol O-methyltransferase on epinephrine. Technically it is a product of epinephrine O-methylation. It is a commonly occurring, pharmacologically and physiologically inactive metabolite of epinephrine. The measurement of plasma free metanephrines is considered to be the best tool in the diagnosis of pheochromocytoma, a rare kind of adrenal medullary neoplasm. In adrenal chromaffin cells, leakage of norepinephrine and epinephrine from storage granules leads to substantial intracellular production of the O-methylated metabolite metanephrine. In fact, the adrenals constitute the single largest source out of any organ system including the liver for circulating metanephrine. In humans, about 93 percent of circulating metanephrine is derived from catecholamines metabolized within adrenal chromaffin cells. (PMID 15317907 ).
Structure
Thumb
Synonyms
ValueSource
(+/-)-metanephrineHMDB
3-Methoxy-adrenalineHMDB
3-MethoxyadrenalineHMDB
3-O-Methyl-adrenalineHMDB
3-O-MethylepinephrineHMDB
4-Hydroxy-3-methoxy-N-methylphenethanolamineHMDB
DL-3-O-MethyladrenalineHMDB
DL-MetanephrineHMDB
m-O-MethyladrenalineHMDB
MetadrenalineHMDB
Chemical FormulaC10H15NO3
Average Molecular Weight197.231
Monoisotopic Molecular Weight197.105193351
IUPAC Name4-[1-hydroxy-2-(methylamino)ethyl]-2-methoxyphenol
Traditional Name(+/-)-metanephrine
CAS Registry Number5001-33-2
SMILES
CNCC(O)C1=CC(OC)=C(O)C=C1
InChI Identifier
InChI=1S/C10H15NO3/c1-11-6-9(13)7-3-4-8(12)10(5-7)14-2/h3-5,9,11-13H,6H2,1-2H3
InChI KeyInChIKey=JWJCTZKFYGDABJ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenols and derivatives
Direct ParentMethoxyphenols
Alternative Parents
Substituents
  • Methoxyphenol
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
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 Solubility13.0 mg/mLALOGPS
logP-0.27ALOGPS
logP-0.00068ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)10.05ChemAxon
pKa (Strongest Basic)9.25ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area61.72 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity53.71 m3·mol-1ChemAxon
Polarizability21.13 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-014i-0910000000-a886bef599ae583766b9View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Adrenal Gland
  • Adrenal Medulla
Pathways
NameSMPDB LinkKEGG Link
AlkaptonuriaSMP00169Not Available
Disulfiram PathwaySMP00429Not Available
Dopamine beta-hydroxylase deficiencySMP00498Not Available
HawkinsinuriaSMP00190Not Available
Monoamine oxidase-a deficiency (MAO-A)SMP00533Not Available
Tyrosine MetabolismSMP00006map00350
Tyrosinemia Type ISMP00218Not Available
Tyrosinemia, transient, of the newbornSMP00494Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0016 (0.00018-0.0025) uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0004 uMNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified1.08 +/- 2.95 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified0.0026 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<0.145 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified< 0.467 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.0011 +/- 0.00034 umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
    • West Cadwell, N.J...
    • Basel, Switzerlan...
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00054 +/- 0.002 uMAdult (>18 years old)Not SpecifiedPheochromocytoma details
Associated Disorders and Diseases
Disease References
Pheochromocytoma
  1. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW: Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun;83(6):2175-85. [9626157 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023296
KNApSAcK IDNot Available
Chemspider ID19844
KEGG Compound IDC05588
BioCyc IDNot Available
BiGG ID46078
Wikipedia LinkMetanephrine
NuGOwiki LinkHMDB04063
Metagene LinkHMDB04063
METLIN ID65
PubChem Compound21100
PDB IDNot Available
ChEBI ID144365
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Beck O, Faull KF: Extractive acylation and mass spectrometric assay of 3-methoxytyramine, normetanephrine, and metanephrine in cerebrospinal fluid. Anal Biochem. 1985 Sep;149(2):492-500. [4073504 ]
  2. Goldstein DS, Eisenhofer G, Kopin IJ: Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003 Jun;305(3):800-11. Epub 2003 Mar 20. [12649306 ]
  3. Uchikura K, Horikawa R, Tanimura T, Kabasawa Y: Determination of catecholamines by radioenzymatic assay using ion-pair liquid chromatography. J Chromatogr. 1981 Apr 10;223(1):41-50. [7251775 ]
  4. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW: Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun;83(6):2175-85. [9626157 ]
  5. Eisenhofer G, Kopin IJ, Goldstein DS: Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004 Sep;56(3):331-49. [15317907 ]
  6. Schmidt J, Mohr VD, Metzger P, Zirngibl H: Posttraumatic hypertension secondary to adrenal hemorrhage mimicking pheochromocytoma: case report. J Trauma. 1999 May;46(5):973-5. [10338428 ]
  7. Higa S, Suzuki T, Sakoda S, Kishimoto S, Takaba Y, Nakajima A, Markey SP: Disturbed function of the pineal gland in familial amyloid polyneuropathy. J Neural Transm. 1987;69(1-2):97-103. [3035087 ]
  8. van Dam PS, van Gils A, Canninga-van Dijk MR, de Koning EJ, Hofland LJ, de Herder WW: Sequential ACTH and catecholamine secretion in a phaeochromocytoma. Eur J Endocrinol. 2002 Aug;147(2):201-6. [12153741 ]
  9. Artal R, Platt LD, Kammula RK, Strassner HT, Gratacos J, Golde SH: Sympathoadrenal activity in infants of diabetic mothers. Am J Obstet Gynecol. 1982 Feb 15;142(4):436-9. [7058845 ]
  10. Artal R, Hobel CJ, Lam R, Oddie TH, Fisher DA: Free metanephrine in human amniotic fluid as an index of fetal sympathetic nervous system maturation. Am J Obstet Gynecol. 1979 Feb 15;133(4):452-4. [434011 ]
  11. Kitamura T, Alroy J, Gatmaitan Z, Inoue M, Mikami T, Jansen P, Arias IM: Defective biliary excretion of epinephrine metabolites in mutant (TR-) rats: relation to the pathogenesis of black liver in the Dubin-Johnson syndrome and Corriedale sheep with an analogous excretory defect. Hepatology. 1992 Jun;15(6):1154-9. [1592353 ]
  12. Pagliari R, Cottet-Emard JM, Peyrin L: Determination of free and conjugated normetanephrine and metanephrine in human plasma by high-performance liquid chromatography with electrochemical detection. J Chromatogr. 1991 Jan 18;563(1):23-36. [2061394 ]
  13. Kaplan NM, Kramer NJ, Holland OB, Sheps SG, Gomez-Sanchez C: Single-voided urine metanephrine assays in screening for pheochromocytoma. Arch Intern Med. 1977 Feb;137(2):190-3. [836117 ]
  14. Taylor RL, Singh RJ: Validation of liquid chromatography-tandem mass spectrometry method for analysis of urinary conjugated metanephrine and normetanephrine for screening of pheochromocytoma. Clin Chem. 2002 Mar;48(3):533-9. [11861444 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular weight:
58762.475
Reactions
Metanephrine + Water + Oxygen → 3-Methoxy-4-hydroxyphenylglycolaldehyde + Hydrogen peroxide + Methylaminedetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular weight:
59681.27
Reactions
Metanephrine + Water + Oxygen → 3-Methoxy-4-hydroxyphenylglycolaldehyde + Hydrogen peroxide + Methylaminedetails
General function:
Involved in magnesium ion binding
Specific function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular weight:
30036.77
Reactions
S-Adenosylmethionine + Epinephrine → S-Adenosylhomocysteine + Metanephrinedetails