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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-04-16 17:00:02 UTC
HMDB IDHMDB0000001
Secondary Accession Numbers
  • HMDB00001
  • HMDB0004935
  • HMDB0006703
  • HMDB0006704
  • 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
CN1C=NC(C[C@H](N)C(O)=O)=C1
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:

Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

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-3.1ChemAxon
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
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Saliva
  • Urine
Tissue Location
  • Muscle
  • Skeletal Muscle
Pathways
NameSMPDB/PathwhizKEGG
Histidine MetabolismThumbThumb?image type=greyscaleThumb?image type=simpleMap00340
HistidinemiaThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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
FecesDetected but not Quantified Adult (>18 years old)Both
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
BiospecimenStatusValueAgeSexConditionReferenceDetails
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 IDDB04151
Phenol Explorer Compound 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 ]