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Record Information
Version3.6
Creation Date2006-05-22 15:12:12 UTC
Update Date2016-02-11 01:05:49 UTC
HMDB IDHMDB02820
Secondary Accession NumbersNone
Metabolite Identification
Common NameMethylimidazoleacetic acid
DescriptionMethylimidazoleacetic acid is the main metabolite of histamine. This end product of histamine catabolism is formed by N-methylation in the imidazole ring to methylhistamine by histamine methyltransferase (EC 2.1.1.8) and a subsequent oxidative deamination in the side chain by type B monoamine oxidase (EC 1.4.3.4). From studies is known that as much as 70 to 80 percent of the histamine metabolized in the body is excreted in the urine as Methylimidazoleacetic acid. Thus, urinary Methylimidazoleacetic acid being the major and specific histamine metabolite is a clear marker of any changes in histamine metabolism in the body. The urinary excretion of methylimidazoleacetic acid is considered a reliable indicator of histamine turnover rate in the body. The excretion of Methylimidazoleacetic acid is higher in men than women however; this gender difference is abolished when corrected for creatinine excretion. A possible explanation is that basal histamine turnover is related to body size. There is no significant difference in Methylimidazoleacetic acid excretion between smokers and non-smokers when analysing absolute values (mg/24 h). When using Methylimidazoleacetic acid values corrected for creatinine excretion female smokers have significantly higher Methylimidazoleacetic acid excretion compared to nonsmokers. (PMID: 11411609 , 7130180 , 10350179 , 10202992 ).
Structure
Thumb
Synonyms
ValueSource
1,4-Methyl-imidazoleacetic acidChEBI
1-Methylimidazole-4-acetateChEBI
MethylimidazoleacetateChEBI
Methylimidazoleacetic acidChEBI
tele-Methylimidazoleacetic acidChEBI
1,4-Methyl-imidazoleacetateGenerator
2-(1-Methylimidazol-4-yl)acetateGenerator
1-Methylimidazole-4-acetic acidGenerator
tele-MethylimidazoleacetateGenerator
1,4-MethylimidazoleacetateHMDB
1-Methyl-1H-imidazole-4-acetateHMDB
1-Methyl-1H-imidazole-4-acetic acidHMDB
1-Methyl-4-imidazoleacetateHMDB
1-Methyl-4-imidazoleacetic acidHMDB
Methylimidazole acetateHMDB
MIAAHMDB
N Tau-methylimidazoleacetic acidHMDB
Chemical FormulaC6H8N2O2
Average Molecular Weight140.1399
Monoisotopic Molecular Weight140.05857751
IUPAC Name2-(1-methyl-1H-imidazol-4-yl)acetic acid
Traditional Namemethylimidazoleacetic acid
CAS Registry Number2625-49-2
SMILES
CN1C=NC(CC(O)=O)=C1
InChI Identifier
InChI=1S/C6H8N2O2/c1-8-3-5(7-4-8)2-6(9)10/h3-4H,2H2,1H3,(H,9,10)
InChI KeyInChIKey=ZHCKPJGJQOPTLB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as imidazolyl carboxylic acids and derivatives. These are organic compounds containing a carboxylic acid chain (of at least 2 carbon atoms) linked to an imidazole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentImidazolyl carboxylic acids and derivatives
Alternative Parents
Substituents
  • Imidazolyl carboxylic acid derivative
  • N-substituted imidazole
  • Heteroaromatic compound
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • 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 Solubility5.88 mg/mLALOGPS
logP-0.22ALOGPS
logP-1.2ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)6.45ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.12 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity34.85 m3·mol-1ChemAxon
Polarizability13.69 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 (1 TMS)splash10-00kb-3900000000-50b4d0d53d911c99c819View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0005-9600000000-bfb5120a71bcb59d0595View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0002-9000000000-e8be837208f721108cb5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00l7-9000000000-30049714cfffac75afa8View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Brain
Pathways
NameSMPDB LinkKEGG Link
Histidine MetabolismSMP00044map00340
HistidinemiaSMP00191Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.08457 +/- 0.01364 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.08076 +/- 0.01892 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.02 +/- 0.001 (0.021-0.023) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.022 +/- 0.0021 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0071 +/- 0.0009 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.50 (0.85-2.3) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.58 (0.48-2.82) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.25 (0.79-3.5) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified2.3 +/- 0.14 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothOral cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)FemaleBreast cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPancreatic cancer details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPeriodontal diseases details
UrineDetected and Quantified10.3 umol/mmol creatinineAdult (>18 years old)BothMastocytosis details
Associated Disorders and Diseases
Disease References
Mastocytosis
  1. Martens-Lobenhoffer J, Neumann HJ: Determination of 1-methylhistamine and 1-methylimidazoleacetic acid in human urine as a tool for the diagnosis of mastocytosis. J Chromatogr B Biomed Sci Appl. 1999 Jan 8;721(1):135-40. [10027644 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023069
KNApSAcK IDNot Available
Chemspider ID68319
KEGG Compound IDC05828
BioCyc IDNot Available
BiGG ID46587
Wikipedia LinkNot Available
NuGOwiki LinkHMDB02820
Metagene LinkHMDB02820
METLIN ID3774
PubChem Compound75810
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Martens-Lobenhoffer J, Neumann HJ: Determination of 1-methylhistamine and 1-methylimidazoleacetic acid in human urine as a tool for the diagnosis of mastocytosis. J Chromatogr B Biomed Sci Appl. 1999 Jan 8;721(1):135-40. [10027644 ]
  2. Tsuruta Y, Tomida H, Kohashi K, Ohkura Y: Simultaneous determination of imidazoleacetic acid and N tau- and N pi-methylimidazoleacetic acids in human urine by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1987 Apr 24;416(1):63-9. [3597642 ]
  3. Khandelwal JK, Hough LB, Pazhenchevsky B, Morrishow AM, Green JP: Presence and measurement of methylimidazoleacetic acids in brain and body fluids. J Biol Chem. 1982 Nov 10;257(21):12815-9. [7130180 ]
  4. Yocum MW, Butterfield JH, Gharib H: Increased plasma calcitonin levels in systemic mast cell disease. Mayo Clin Proc. 1994 Oct;69(10):987-90. [7934197 ]
  5. Prell GD, Khandelwal JK, Burns RS, LeWitt PA, Green JP: Elevated levels of histamine metabolites in cerebrospinal fluid of aging, healthy humans. Compr Gerontol [A]. 1988 Oct;2(3):114-9. [2906817 ]
  6. Prell GD, Green JP, Kaufmann CA, Khandelwal JK, Morrishow AM, Kirch DG, Linnoila M, Wyatt RJ: Histamine metabolites in cerebrospinal fluid of patients with chronic schizophrenia: their relationships to levels of other aminergic transmitters and ratings of symptoms. Schizophr Res. 1995 Jan;14(2):93-104. [7711000 ]
  7. Granerus G, Roupe G, Swanbeck G: Decreased urinary histamine metabolite after successful PUVA treatment of urticaria pigmentosa. J Invest Dermatol. 1981 Jan;76(1):1-3. [7462662 ]
  8. Swahn CG, Sedvall G: Identification and determination of 1-methylimidazole-4-acetic acid in human cerebrospinal fluid by gas chromatography-mass spectrometry. J Neurochem. 1983 Mar;40(3):688-96. [6827268 ]
  9. Johansson AC, Lonnqvist B, Granerus G: The relationship between body size and the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid in man. Inflamm Res. 2001 Apr;50 Suppl 2:S70-1. [11411609 ]
  10. Granerus G, Lonnqvist B, Stenstrom M: No sex difference in the urinary excretion of the histamine metabolite methylimidazoleacetic acid (MeImAA) when corrected for creatinine excretion. Inflamm Res. 1999 Apr;48 Suppl 1:S92-3. [10350179 ]
  11. Granerus G, Lonnqvist B, Wass U: Determination of the histamine metabolite tele-methylimidazoleacetic acid and of creatinine in urine by the same HPLC system. Inflamm Res. 1999 Feb;48(2):75-80. [10202992 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.
Gene Name:
ALDH3A1
Uniprot ID:
P30838
Molecular weight:
50394.57
Reactions
Methylimidazole acetaldehyde + NAD + Water → Methylimidazoleacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
Gene Name:
ALDH1A3
Uniprot ID:
P47895
Molecular weight:
56107.995
Reactions
Methylimidazole acetaldehyde + NAD + Water → Methylimidazoleacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ALDH3B2
Uniprot ID:
P48448
Molecular weight:
42623.62
Reactions
Methylimidazole acetaldehyde + NAD + Water → Methylimidazoleacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. May use both NADP(+) and NAD(+) as cofactors. May have a protective role against the cytotoxicity induced by lipid peroxidation.
Gene Name:
ALDH3B1
Uniprot ID:
P43353
Molecular weight:
51839.245
Reactions
Methylimidazole acetaldehyde + NAD + Water → Methylimidazoleacetic acid + NADH + Hydrogen Iondetails