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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-12-07 01:05:49 UTC
HMDB IDHMDB0000001
Secondary Accession Numbers
  • HMDB00001
  • HMDB04935
  • HMDB06703
  • HMDB06704
Metabolite Identification
Common Name1-Methylhistidine
DescriptionOne-methylhistidine (1-MHis) is derived mainly from the anserine of dietary flesh sources, especially poultry. The enzyme, carnosinase, splits anserine into b-alanine and 1-MHis. High levels of 1-MHis tend to inhibit the enzyme carnosinase and increase anserine levels. Conversely, genetic variants with deficient carnosinase activity in plasma show increased 1-MHis excretions when they consume a high meat diet. Reduced serum carnosinase activity is also found in patients with Parkinson's disease and multiple sclerosis and patients following a cerebrovascular accident. Vitamin E deficiency can lead to 1-methylhistidinuria from increased oxidative effects in skeletal muscle. 1-Methylhistidine is a biomarker for the consumption of meat, especially red meat.
Structure
Thumb
Synonyms
ValueSource
(2S)-2-amino-3-(1-Methyl-1H-imidazol-4-yl)propanoic acidChEBI
1-MethylhistidineChEBI
Pi-methylhistidineChEBI
(2S)-2-amino-3-(1-Methyl-1H-imidazol-4-yl)propanoateGenerator
1 MethylhistidineHMDB
1-Methyl histidineHMDB
1-Methyl-histidineHMDB
1-Methyl-L-histidineHMDB
1-MHisHMDB
1-N-Methyl-L-histidineHMDB
L-1-MethylhistidineHMDB
N1-Methyl-L-histidineHMDB
1-Methylhistidine dihydrochlorideMeSH
Chemical FormulaC7H11N3O2
Average Molecular Weight169.1811
Monoisotopic Molecular Weight169.085126611
IUPAC Name(2S)-2-amino-3-(1-methyl-1H-imidazol-4-yl)propanoic acid
Traditional Name1 methylhistidine
CAS Registry Number332-80-9
SMILES
[H][C@](N)(CC1=CN(C)C=N1)C(O)=O
InChI Identifier
InChI=1S/C7H11N3O2/c1-10-3-5(9-4-10)2-6(8)7(11)12/h3-4,6H,2,8H2,1H3,(H,11,12)/t6-/m0/s1
InChI KeyBRMWTNUJHUMWMS-LURJTMIESA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as histidine and derivatives. These are compounds containing cysteine or a derivative thereof resulting from reaction of cysteine 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 ParentHistidine and derivatives
Alternative Parents
Substituents
  • Histidine or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Imidazolyl carboxylic acid derivative
  • Aralkylamine
  • N-substituted imidazole
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Amino acid
  • Carboxylic acid
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Primary amine
  • Primary aliphatic amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

  Health condition:

    Metabolism and nutrition disorders:

Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Tissue and substructures:

Source:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point249http://download.cappchem.com/data/Properties-of-Amino-Acids.pdf
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.93 g/LALOGPS
logP-3ALOGPS
logP-3.1ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)1.96ChemAxon
pKa (Strongest Basic)9.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area81.14 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity42.39 m³·mol⁻¹ChemAxon
Polarizability17.11 ųChemAxon
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 (2 TMS)splash10-0002-9610000000-d0147d3e28362f91174aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0gbd-4941000000-cee19577c72eecd95aecView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0002-9610000000-d0147d3e28362f91174aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0gbd-4941000000-cee19577c72eecd95aecView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00dm-9500000000-e50450f2dc8a5d4b3655View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9310000000-d6f7eb07e6f5ecb74263View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00di-0900000000-037d24a7d65676b7e356View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-0900000000-03e99316bd6c098f5d11View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00ea-9800000000-a33c82a1c91f56d372feView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-695bcc2d0a01df2d7521View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0900000000-4eea9cf6f12f18d06f98View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05us-9300000000-072d6fe7a7a03cd7390bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-1900000000-57f1e30ae8b606ea5f5cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01b9-5900000000-ff71b6d300a9ee595b3cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0adj-9300000000-e045823003ab541d5b1eView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Muscle
  • Skeletal Muscle
Pathways
NameSMPDB/PathwhizKEGG
Histidine MetabolismPw000043Pw000043 greyscalePw000043 simpleMap00340
HistidinemiaPw000113Pw000113 greyscalePw000113 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified7.7 +/- 1.9 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified14.4 +/- 2.3 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified19.6 +/- 2.6 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified12.7 +/- 2.9 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified20.2 +/- 4.0 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified9.1 +/- 7.2 uMChildren (1-13 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified4.0 +/- 8.0 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified4.0 +/- 1.74 uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Not SpecifiedBoth
Normal
details
SalivaDetected and Quantified26.34 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified10-17 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected but not Quantified Not AvailableMaleNormal details
UrineDetected and Quantified17.74-153.77 umol/mmol creatinineAdult (>18 years old)BothNormal
    • David F. Putnam C...
details
UrineDetected and Quantified8.3 (2.4-28.4) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified15.9 +/- 19.5 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified46.0833 +/- 53.432 umol/mmol creatinineAdult (>18 years old)Female
Normal
details
UrineDetected and Quantified11-16 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified45.473 +/- 41.617 umol/mmol creatinineAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified15.919 +/- 19.503 umol/mmol creatinineAdult (>18 years old)Female
Normal
details
UrineDetected and Quantified4.635 umol/mmol creatinineAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified33.624 +/- 36.360 umol/mmol creatinineAdult (>18 years old)Female
Normal
details
UrineDetected and Quantified28.0954 +/- 31.826 umol/mmol creatinineAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified2.340 +/- 5.0764 umol/mmol creatinineAdult (>18 years old)Female
Normal
details
UrineDetected and Quantified1.334 +/- 2.759 umol/mmol creatinineAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified30.0 +/- 43.0 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified4.6 +/- 2.7 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified2.3 +/- 5.1 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified46.1 +/- 53.5 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified15.9 +/- 19.5 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified28.1 +/- 31.8 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified1.3 +/- 2.76 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified45.5 +/- 41.6 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified33.6 +/- 36.4 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified21.329 +/- 12.971 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected but not Quantified Adult (>18 years old)Male
Normal
details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified51.2 +/- 17.6 uMAdult (>18 years old)Female
Pregnancy with fetuses with trisomy 18
details
BloodDetected and Quantified43.4 +/- 22.3 uMAdult (>18 years old)FemalePregnancy details
BloodDetected and Quantified50.7 (12.9) uMAdult (>18 years old)FemaleEarly preeclampsia details
BloodDetected and Quantified50.0 (14.6) uMAdult (>18 years old)FemalePregnancy details
BloodDetected and Quantified28.8 +/- 18.2 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified83.1 +/- 21.7 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified70.3 (40.0) uMAdult (>18 years old)FemaleLate-onset preeclampsia details
BloodDetected and Quantified38.9 (20.3) uMAdult (>18 years old)FemalePregnancy details
BloodDetected and Quantified10.66 +/- 2.68 uMElderly (>65 years old)Both
Alzheimer's disease
details
BloodDetected and Quantified40.4 (12.3) uMAdult (>18 years old)FemaleDown syndrome pregnancy details
BloodDetected and Quantified32.7 (13.7) uMAdult (>18 years old)FemalePregnancy details
Cerebrospinal Fluid (CSF)Detected and Quantified2.6 +/- 1.13 uMAdult (>18 years old)BothAlzheimer's disease details
UrineDetected and Quantified10.9 +/- 10.1 umol/mmol creatinineAdult (>18 years old)BothObesity details
UrineDetected and Quantified17.5 +/- 25.7 umol/mmol creatinineAdult (>18 years old)BothDiabetes details
UrineDetected and Quantified15.7 +/- 4.04 umol/mmol creatinineAdult (>18 years old)Both
Alzheimer's disease
details
UrineDetected and Quantified18.299 +/- 16.521 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified40 +/- 2.6 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
UrineDetected and Quantified31 +/- 11 umol/mmol creatinineAdult (>18 years old)BothMaple syrup urine disease details
UrineDetected and Quantified50.3 +/- 9.9 umol/mmol creatinineAdult (>18 years old)BothAminoaciduria details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. [PubMed:17031479 ]
Diabetes mellitus type 2
  1. Tuma P, Samcova E, Balinova P: Determination of 3-methylhistidine and 1-methylhistidine in untreated urine samples by capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 5;821(1):53-9. [PubMed:15899597 ]
Kidney disease
  1. Raj DS, Ouwendyk M, Francoeur R, Pierratos A: Plasma amino acid profile on nocturnal hemodialysis. Blood Purif. 2000;18(2):97-102. [PubMed:10838467 ]
Obesity
  1. Tuma P, Samcova E, Balinova P: Determination of 3-methylhistidine and 1-methylhistidine in untreated urine samples by capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 5;821(1):53-9. [PubMed:15899597 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012119
KNApSAcK IDNot Available
Chemspider ID83153
KEGG Compound IDC01152
BioCyc IDCPD-1823
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID3741
PubChem Compound92105
PDB IDHIC
ChEBI ID50599
References
Synthesis ReferenceJain, Rahul; Cohen, Louis A. Regiospecific alkylation of histidine and histamine at N-1 (t).Tetrahedron (1996), 52(15), 5363-70.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Colombani PC, Kovacs E, Frey-Rindova P, Frey W, Langhans W, Arnold M, Wenk C: Metabolic effects of a protein-supplemented carbohydrate drink in marathon runners. Int J Sport Nutr. 1999 Jun;9(2):181-201. [PubMed:10362454 ]
  2. Nicholson JK, Foxall PJ, Spraul M, Farrant RD, Lindon JC: 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem. 1995 Mar 1;67(5):793-811. [PubMed:7762816 ]
  3. Myint T, Fraser GE, Lindsted KD, Knutsen SF, Hubbard RW, Bennett HW: Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists. Am J Epidemiol. 2000 Oct 15;152(8):752-5. [PubMed:11052553 ]
  4. Giesecke K, Magnusson I, Ahlberg M, Hagenfeldt L, Wahren J: Protein and amino acid metabolism during early starvation as reflected by excretion of urea and methylhistidines. Metabolism. 1989 Dec;38(12):1196-200. [PubMed:2593832 ]
  5. Vranic L, Granic P, Rajic Z: Basic amino acid in the pathogenesis of caries. Acta Stomatol Croat. 1991;25(2):71-6. [PubMed:1819935 ]
  6. Sjolin J, Stjernstrom H, Henneberg S, Hambraeus L, Friman G: Evaluation of urinary 3-methylhistidine excretion in infection by measurements of 1-methylhistidine and the creatinine ratios. Am J Clin Nutr. 1989 Jan;49(1):62-70. [PubMed:2912013 ]
  7. COCKS DH, DENNIS PO, NELSON TH: ISOLATION OF 3-METHYL HISTIDINE FROM WHALEMEAT EXTRACT AND THE PREPARATION OF SOME DERIVATIVES. Nature. 1964 Apr 11;202:184-5. [PubMed:14156296 ]
  8. Dohm GL, Williams RT, Kasperek GJ, van Rij AM: Increased excretion of urea and N tau -methylhistidine by rats and humans after a bout of exercise. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jan;52(1):27-33. [PubMed:7061274 ]
  9. Garlick PJ, McNurlan MA, Bark T, Lang CH, Gelato MC: Hormonal regulation of protein metabolism in relation to nutrition and disease. J Nutr. 1998 Feb;128(2 Suppl):356S-359S. [PubMed:9478024 ]
  10. Tuma P, Samcova E, Balinova P: Determination of 3-methylhistidine and 1-methylhistidine in untreated urine samples by capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 5;821(1):53-9. [PubMed:15899597 ]
  11. Dunnett M, Harris RC: High-performance liquid chromatographic determination of imidazole dipeptides, histidine, 1-methylhistidine and 3-methylhistidine in equine and camel muscle and individual muscle fibres. J Chromatogr B Biomed Sci Appl. 1997 Jan 10;688(1):47-55. [PubMed:9029312 ]
  12. Betto P, Ricciarello G, Pichini S, Dello Strologo L, Rizzoni G: High-performance liquid chromatography-electrochemical detection of 3-methylhistidine in human urine. J Chromatogr. 1992 Dec 23;584(2):256-60. [PubMed:1484110 ]

Enzymes

General function:
Involved in metallopeptidase activity
Specific function:
Preferential hydrolysis of the beta-Ala-|-His dipeptide (carnosine), and also anserine, Xaa-|-His dipeptides and other dipeptides including homocarnosine
Gene Name:
CNDP1
Uniprot ID:
Q96KN2
Molecular weight:
56691.6
References
  1. Fleisher LD, Rassin DK, Wisniewski K, Salwen HR: Carnosinase deficiency: a new variant with high residual activity. Pediatr Res. 1980 Apr;14(4 Pt 1):269-71. [PubMed:7375183 ]
General function:
Involved in protein methyltransferase activity
Specific function:
Methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in some proteins
Gene Name:
PRMT3
Uniprot ID:
O60678
Molecular weight:
59902.7
References
  1. Raghavan M, Lindberg U, Schutt C: The use of alternative substrates in the characterization of actin-methylating and carnosine-methylating enzymes. Eur J Biochem. 1992 Nov 15;210(1):311-8. [PubMed:1446680 ]