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Record Information
Created at2005-11-16 15:48:42 UTC
Updated at2021-10-07 20:38:32 UTC
NP-MRD IDNP0000907
Secondary Accession NumbersNone
Natural Product Identification
Common Name3-Methylhistidine
Description3-Methylhistidine, also known as 3-MHis or 3MH, belongs to the class of organic compounds known as histidine and derivatives. 3MH is also classified as a methylamino acid. Methylamino acids are primarily proteogenic amino acids (found in proteins) which have been methylated (in situ) on their side chains by various methyltransferase enzymes. 3-Methylhistidine is also classified as a member of the class of compounds known as L-alpha-amino acids. L-alpha-Amino acids are alpha amino acids which have the L-configuration of the alpha-carbon atom. Amino acids are organic compounds that contain amino (–NH2) and carboxyl (–COOH) functional groups, along with a side chain (R group) specific to each amino acid. 3-Methylhistidine is generated from histidine residues found in proteins. Histidine can be methylated at either the N1 or N3 position of its imidazole ring, yielding the isomers 1-methylhistidine (1MH; also referred to as pi-methylhistidine) or 3-methylhistidine (3MH; tau-methylhistidine), respectively. There is considerable confusion with regard to the nomenclature of the methylated nitrogen atoms on the imidazole ring of histidine and other histidine-containing peptides such as anserine. In particular, older literature (mostly prior to the year 2000) designated anserine (Npi methylated) as beta-alanyl-N1-methyl-histidine, whereas according to standard IUPAC nomenclature, anserine is correctly named as beta-alanyl-N3-methyl-histidine. As a result, many papers published prior to the year 2000 incorrectly identified 1MH as a specific marker for dietary consumption or various pathophysiological effects when they really were referring to 3MH (PMID: 24137022 ). Histidine methylation on the 3- or tau site is mediated by the enzyme known as METTL18. METTL18 is a nuclear methyltransferase protein that contains a functional nuclear localization signal and accumulates in nucleoli. Urinary concentrations of 3-methylhistidine can be used as a biomarker for skeletal muscle protein breakdown in humans who have been subject to muscle injury (PMID: 16079625 ). 3-Methylhistidine is formed by the posttranslational methylation of histidine residues of the main myofibrillar proteins actin and myosin. During protein catabolism, 3-methylhistidine is released but cannot be reutilized. Therefore, the plasma concentration and urine excretion of 3-methylhistidine are sensitive markers of myofibrillar protein degradation (PMID: 32235743 ). Approximately 75% of 3-methylhistidine is estimated to originate from skeletal muscle (PMID: 32235743 ). In addition to the degradation of muscle proteins, the 3-methylhistidine level is affected by the degradation of intestinal proteins and meat intake. 3-Methylhistidine exists in all eukaryotes, ranging from yeast to humans. In humans, 3-methylhistidine is involved in methylhistidine metabolism. 3-Methylhistidine has been found to be associated with several diseases such as diabetes mellitus type 2, eosinophilic esophagitis, and kidney disease. The normal concentration of 3-methylhistidine in the urine of healthy adult humans has been detected and quantified in a range of 3.63–69.27 Micromoles per millimole (umol/mmol) of creatinine, with most studies reporting the average urinary concentration between 15–20 umol/mmol of creatinine. The average concentration of 3-methylhistidine in human blood plasma has been detected and quantified at 2.85 Micromolar (uM) with a range of 0.0–5.9 UM. As a general rule, urinary 1MH is associated with white meat intake (p< 0.001), Whereas urinary 3MH is associated with red meat intake (p< 0.001) (PMID: 34091671 ).
(2S)-2-Amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acidChEBI
3-Methylhistidine hydrideHMDB
3-Methylhistidine dihydrochlorideHMDB
N Tau-methylhistidineHMDB
Chemical FormulaC7H11N3O2
Average Mass169.1811 Da
Monoisotopic Mass169.08513 Da
IUPAC Name(2S)-2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acid
Traditional Name3,methylhistidine
CAS Registry Number368-16-1
InChI Identifier
Spectrum TypeDescriptionDepositor IDDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Wishart Lab2021-06-20View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart Lab2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, simulated)V.dorna832021-08-02View Spectrum
Species of Origin
  • Animalia
  • Species Where Detected
    Species NameSourceReference
    Homo sapiens (Urine)KNApSAcK Database
    Chemical Taxonomy
    Description Belongs to the class of organic compounds known as histidine and derivatives. Histidine and derivatives 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
    • 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
    Physical Properties
    Experimental Properties
    Melting PointNot AvailableNot Available
    Boiling PointNot AvailableNot Available
    Water Solubility200 mg/mL at 25 °CBeilstein Handbook of Organic Chemistry (Handbuch der Organischen Chemie), 4th Edition
    LogPNot AvailableNot Available
    Predicted Properties
    Water Solubility6.93 g/LALOGPS
    pKa (Strongest Acidic)1.96ChemAxon
    pKa (Strongest Basic)9.43ChemAxon
    Physiological Charge0ChemAxon
    Hydrogen Acceptor Count4ChemAxon
    Hydrogen Donor Count2ChemAxon
    Polar Surface Area81.14 ŲChemAxon
    Rotatable Bond Count3ChemAxon
    Refractivity42.96 m³·mol⁻¹ChemAxon
    Polarizability16.58 ųChemAxon
    Number of Rings1ChemAxon
    Rule of FiveYesChemAxon
    Ghose FilterNoChemAxon
    Veber's RuleNoChemAxon
    MDDR-like RuleNoChemAxon
    HMDB IDHMDB0000479
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB093613
    KNApSAcK IDC00050709
    Chemspider ID58494
    KEGG Compound IDC01152
    BioCyc IDNot Available
    BiGG IDNot Available
    Wikipedia Link3-Methylhistidine
    METLIN ID5466
    PubChem Compound64969
    PDB IDNot Available
    ChEBI ID27596
    Good Scents IDrw1191881
    General References
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