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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2022-10-24 15:31:28 UTC
HMDB IDHMDB0000001
Secondary Accession Numbers
  • HMDB00001
  • HMDB0004935
  • HMDB0006703
  • HMDB0006704
  • HMDB04935
  • HMDB06703
  • HMDB06704
Metabolite Identification
Common Name1-Methylhistidine
Description1-Methylhistidine, also known as 1-MHis, 1MH, tau-methylhistidine or tele-methylhistidine, belongs to the class of organic compounds known as histidine and derivatives. 1MH 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. 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 tau-methylhistidine, according to IUPAC) or 3-methylhistidine (3MH; pi-methylhistidine, according to IUPAC), respectively. There is considerable confusion with regard to the nomenclature of the methylated nitrogen atoms on the imidazole ring of histidine in histidine-containing proteins (such as actin and myosin) as well as histidine-containing peptides (such as anserine and ophidine/balenine). In particular, older literature (mostly prior to the year 2000) as well as most biochemists and nutrition scientists incorrectly number the imidazole nitrogen atom most proximal to the side chain beta-carbon as 1 or N1, while organic chemists correctly designate it as 3 or N3. As a result, biochemists and nutrition scientists historically designated anserine (Npi-methylated) as beta-alanyl-N1-methylhistidine (or beta-alanyl-1-methylhistidine), whereas according to standard IUPAC nomenclature, anserine is correctly named as beta-alanyl-N3-methylhistidine. As a result, for several decades, many papers incorrectly identified 1MH as a specific marker for dietary consumption or various pathophysiological effects when they really are referring to 3MH – and vice versa (PMID: 24137022 ). To help resolve this issue the IUPAC commission (PMID: 6743224 and IUPAC Compendium of Chemical Terminology, 2nd ed. (the 'Gold Book'). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997)) revised the nomenclature for histidine and introduced the terms pi (for prox or pros – near) and tau (for tele – far) to label the imidazole nitrogens in histidine. Therefore, the pi nitrogen is the nitrogen closest to the side chain beta carbon (atom #3 or N3) while the tau nitrogen is most distant from the side chain beta carbon (atom #1 or N1). IUPAC's goal is for the global community to refer to the molecule depicted here is as 'tau-methylhistidine' with the hope that the archaic term, 1-methylhistidine will eventually disappear. Unfortunately, this has not happened and confusion still persists. Older versions of the HMDB (prior to 2022) as well as current versions of some databases, such as PubChem, KEGG, and UniProt, indicate that an acceptable synonym for 1MH is pi-methylhistidine or otherwise somehow equate 1MH and 3MH. This is incorrect and it continues to sow confusion. Indeed, a key paper that identified METTL9 as the enzyme responsible for pi-methylation of histidine in most vertebrates also incorrectly labeled the METTL9 product as 1MH (PMID: 33563959 ). Similarly, a key paper that identified METTL18 as the enzyme responsible for tau-methylation of histidine incorrectly labelled the METTL18 product as 3MH (PMID: 33693809 ). Likewise, many members of the biochemical/nutrition community still incorrectly refer to 1MH as pi-methlyhistidine and 3MH as tau-methylhistidine. This has led to even more confusion. To maintain consistency for this compound description, all papers cited herein that incorrectly refer to 3MH as 1MH and vice versa, will have their conclusions re-stated and the citation will be marked with the phrase '3MH/1MH switch'. 1MH is a free amino acid arising from the proteolysis of 1MH-containing proteins and peptides. It is not synthesized on its own, nor can it be incorporated into proteins as an amino acid. However, it can be incorporated into certain dipeptides through the action of the enzyme known as carnosine synthase I. 1MH can only be generated from histidine residues through the action of methyltransferases as a protein post-translational modification event. Histidine methylation on the 1- or tau site of histidine-containing proteins is mediated by at least two enzymes: SETD3 (PMID: 30526847 ) and METTL18 (3MH/1MH switch - PMID: 33693809 ). SETD3, or SET domain-containing protein 3, is a protein-histidine N-methyltransferase that specifically mediates 1-methylhistidine (tau-methylhistidine) methylation of actin at 'His-73' (PMID: 30526847 ; 3MH/1MH switch - PMID: 30626964 ). SETD3 is a methyltransferase that uses S-adenosyl-L-methionine to transfer the methyl group to histidine at the tau position. Histidine methylation of actin His-73 is required for smooth muscle contraction of the laboring uterus during delivery (3MH/1MH switch - PMID: 30626964 ). It also reduces the nucleotide exchange rate on actin monomers and modestly accelerates actin filament assembly (3MH/1MH switch - PMID: 30626964 ). SETD3-mediated histidine methylation appears to occur in all higher eukaryotes with actin, from plants to insects to vertebrates. Within cells, SETD3 is found in the cytoplasm and nucleus. In contrast to SETD3, METTL18 is a nuclear methyltransferase protein that contains a functional nuclear localization signal and accumulates in nucleoli. Specifically, METTL18 is a seven β-strand (7BS) methyltransferase that uses S-adenosyl-L-methionine to transfer the methyl group to the tau position of His-245 on ribosomal protein L3, RPL3 (3MH/1MH switch - PMID: 33693809 ). METTL18 is highly conserved and found in essentially all eukaryotes (from yeast to humans). METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function (3MH/1MH switch - PMID: 33693809 ). Other proteins that are known to have 1MH modifications include myosin and myosin kinase. In addition to these tau-His-methylated proteins, a specialized dipeptide called ophidine (balenine) that consists of beta-alanine and 1MH is also known (PMID: 24137022 ). This methylated analog of carnosine, which is naturally produced in the liver via the enzyme carnosine synthase I (PMID: 20097752 ), is especially abundant in the skeletal muscles and brains of whales and dolphins but almost completely absent in other vertebrates (PMID: 24137022 ). Ophidine, like its homologs anserine and carnosine, is believed to act as a pH buffer (for lactic acid generated by muscles), an antiglycating agent, and an antioxidant. Neither ophidine nor anserine are produced in humans, with humans being the only vertebrate not producing (or producing very little) methylated histidine versions of carnosine (PMID: 24137022 ). Because 1MH is so abundant in skeletal muscle tissues (being found in the main myofibrillar proteins actin and myosin), the urinary concentrations of 1-methylhistidine can be used as a biomarker for skeletal muscle protein breakdown, especially for those who have been subject to muscle injury (3MH/1MH switch - PMID: 16079625 ). During protein catabolism, 1-methylhistidine is released but cannot be reutilized. Therefore, the plasma concentration and urine excretion of 1-methylhistidine serve as sensitive markers of myofibrillar protein degradation (3MH/1MH switch - PMID: 32235743 ). Approximately 75% of 1-methylhistidine in the human body is estimated to originate from skeletal muscle (3MH/1MH switch - PMID: 32235743 ). In addition to the degradation of muscle proteins, the 1-methylhistidine level can be moderately affected by the degradation of intestinal proteins and meat intake. 1-Methylhistidine has been found to be associated with several diseases such as Alzheimer's disease, preeclampsia, obesity, kidney disease. The normal concentration of 1-methylhistidine in the urine of healthy adult humans has been detected and quantified in a range of 17.7-153.8 micromoles per millimole (umol/mmol) of creatinine, with most studies reporting the average urinary concentration between 25-40 umol/mmol of creatinine. The average concentration of 1-methylhistidine in human blood plasma has been detected and quantified at 12.7 micromolar (uM) with a range of 9.8-15.6 uM. As a general rule, urinary 3MH is associated with white meat intake (p< 0.001), whereas urinary 1MH is associated with red meat intake (p< 0.001) (3MH/1MH switch - PMID: 34091671 ).
Structure
Data?1666625488
Synonyms
ValueSource
(2S)-2-Amino-3-(1-methyl-1H-imidazol-4-yl)propanoic acidChEBI
(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 dihydrochlorideHMDB
1-MethylhistidineChEBI
Tau methylhistidineHMDB
N(Tau)-methylhistidineHMDB
Tau-methyl-L-histidineHMDB
N Tau-methylhistidineHMDB
Chemical FormulaC7H11N3O2
Average Molecular Weight169.1811
Monoisotopic Molecular Weight169.085126611
IUPAC Name2-amino-3-(1-methyl-1H-imidazol-4-yl)propanoic acid hydrate
Traditional Name4-methyl-histidine hydrate
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
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
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
Disposition
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point249 °Chttp://download.cappchem.com/data/Properties-of-Amino-Acids.pdf
Boiling PointNot AvailableNot Available
Water Solubility200 g/kghttp://download.cappchem.com/data/Properties-of-Amino-Acids.pdf
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M-H]-MetCCS_train_neg139.63930932474
[M+H]+Astarita_pos129.030932474
[M+H]+MetCCS_test_pos133.10330932474
[M-H]-Not Available139.639http://allccs.zhulab.cn/database/detail?ID=AllCCS00000001
[M+H]+Not Available133.594http://allccs.zhulab.cn/database/detail?ID=AllCCS00000001
Predicted Molecular 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
Polarizability17.1 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+138.63431661259
DarkChem[M-H]-139.48431661259
AllCCS[M+H]+138.13732859911
AllCCS[M-H]-135.50932859911
DeepCCS[M+H]+139.67130932474
DeepCCS[M-H]-137.51730932474
DeepCCS[M-2H]-171.18730932474
DeepCCS[M+Na]+145.58330932474
AllCCS[M+H]+138.132859911
AllCCS[M+H-H2O]+133.932859911
AllCCS[M+NH4]+142.032859911
AllCCS[M+Na]+143.232859911
AllCCS[M-H]-135.532859911
AllCCS[M+Na-2H]-136.732859911
AllCCS[M+HCOO]-138.132859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
1-MethylhistidineCN1C=NC(C[C@H](N)C(O)=O)=C12786.8Standard polar33892256
1-MethylhistidineCN1C=NC(C[C@H](N)C(O)=O)=C11704.0Standard non polar33892256
1-MethylhistidineCN1C=NC(C[C@H](N)C(O)=O)=C11882.5Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
1-Methylhistidine,1TMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C)=C11756.4Semi standard non polar33892256
1-Methylhistidine,1TMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C)=C11722.8Standard non polar33892256
1-Methylhistidine,1TMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C)=C12700.3Standard polar33892256
1-Methylhistidine,1TMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O)=C11822.4Semi standard non polar33892256
1-Methylhistidine,1TMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O)=C11778.9Standard non polar33892256
1-Methylhistidine,1TMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O)=C12717.7Standard polar33892256
1-Methylhistidine,2TMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O[Si](C)(C)C)=C11829.7Semi standard non polar33892256
1-Methylhistidine,2TMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O[Si](C)(C)C)=C11805.4Standard non polar33892256
1-Methylhistidine,2TMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C)C(=O)O[Si](C)(C)C)=C12309.2Standard polar33892256
1-Methylhistidine,2TMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C)[Si](C)(C)C)=C11982.1Semi standard non polar33892256
1-Methylhistidine,2TMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C)[Si](C)(C)C)=C11928.0Standard non polar33892256
1-Methylhistidine,2TMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C)[Si](C)(C)C)=C12475.5Standard polar33892256
1-Methylhistidine,3TMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C)N([Si](C)(C)C)[Si](C)(C)C)=C12034.9Semi standard non polar33892256
1-Methylhistidine,3TMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C)N([Si](C)(C)C)[Si](C)(C)C)=C11962.9Standard non polar33892256
1-Methylhistidine,3TMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C)N([Si](C)(C)C)[Si](C)(C)C)=C12190.2Standard polar33892256
1-Methylhistidine,1TBDMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C(C)(C)C)=C12006.1Semi standard non polar33892256
1-Methylhistidine,1TBDMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C(C)(C)C)=C11955.4Standard non polar33892256
1-Methylhistidine,1TBDMS,isomer #1CN1C=NC(C[C@H](N)C(=O)O[Si](C)(C)C(C)(C)C)=C12783.2Standard polar33892256
1-Methylhistidine,1TBDMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O)=C12057.6Semi standard non polar33892256
1-Methylhistidine,1TBDMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O)=C12027.5Standard non polar33892256
1-Methylhistidine,1TBDMS,isomer #2CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O)=C12753.7Standard polar33892256
1-Methylhistidine,2TBDMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O[Si](C)(C)C(C)(C)C)=C12267.7Semi standard non polar33892256
1-Methylhistidine,2TBDMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O[Si](C)(C)C(C)(C)C)=C12257.2Standard non polar33892256
1-Methylhistidine,2TBDMS,isomer #1CN1C=NC(C[C@H](N[Si](C)(C)C(C)(C)C)C(=O)O[Si](C)(C)C(C)(C)C)=C12465.1Standard polar33892256
1-Methylhistidine,2TBDMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12421.6Semi standard non polar33892256
1-Methylhistidine,2TBDMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12352.3Standard non polar33892256
1-Methylhistidine,2TBDMS,isomer #2CN1C=NC(C[C@@H](C(=O)O)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12557.0Standard polar33892256
1-Methylhistidine,3TBDMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12660.0Semi standard non polar33892256
1-Methylhistidine,3TBDMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12590.7Standard non polar33892256
1-Methylhistidine,3TBDMS,isomer #1CN1C=NC(C[C@@H](C(=O)O[Si](C)(C)C(C)(C)C)N([Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)=C12475.7Standard polar33892256
Spectra
Biological Properties
Cellular Locations
  • Cytoplasm
  • Nucleus
  • Myofibril
  • Nucleoli
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue Locations
  • Skeletal Muscle
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
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 QuantifiedNot QuantifiedNot SpecifiedBoth
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified2.15-162.32 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified10-17 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected but not QuantifiedNot QuantifiedNot AvailableMaleNormal details
UrineDetected and Quantified1.36-175.22 umol/mmol creatinineAdolescent (13-18 years old)Not SpecifiedNormal 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 Quantified2.60-151.46 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal 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 Quantified1.92-47.39 umol/mmol creatinineInfant (0-1 year old)Not SpecifiedNormal 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 Quantified2.036-184.27 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal 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 Quantified18.55-145.2 umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified21.329 +/- 12.971 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Analysis of 30 no...
details
UrineDetected and Quantified53.18(22.81-139.9) umol/mmol creatinineNewborn (0-30 days old)FemaleNormal details
UrineDetected and Quantified47.06(17.31-146.8) umol/mmol creatinineNewborn (0-30 days old)MaleNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.13-166.96 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Male
Normal
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>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
    • Analysis of 30 no...
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
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 ]
Early preeclampsia
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: Metabolomics and first-trimester prediction of early-onset preeclampsia. J Matern Fetal Neonatal Med. 2012 Oct;25(10):1840-7. doi: 10.3109/14767058.2012.680254. Epub 2012 Apr 28. [PubMed:22494326 ]
Pregnancy
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: Metabolomics and first-trimester prediction of early-onset preeclampsia. J Matern Fetal Neonatal Med. 2012 Oct;25(10):1840-7. doi: 10.3109/14767058.2012.680254. Epub 2012 Apr 28. [PubMed:22494326 ]
  2. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: First-trimester metabolomic detection of late-onset preeclampsia. Am J Obstet Gynecol. 2013 Jan;208(1):58.e1-7. doi: 10.1016/j.ajog.2012.11.003. Epub 2012 Nov 13. [PubMed:23159745 ]
  3. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: Metabolomic analysis for first-trimester Down syndrome prediction. Am J Obstet Gynecol. 2013 May;208(5):371.e1-8. doi: 10.1016/j.ajog.2012.12.035. Epub 2013 Jan 8. [PubMed:23313728 ]
  4. Bahado-Singh RO, Akolekar R, Chelliah A, Mandal R, Dong E, Kruger M, Wishart DS, Nicolaides K: Metabolomic analysis for first-trimester trisomy 18 detection. Am J Obstet Gynecol. 2013 Jul;209(1):65.e1-9. doi: 10.1016/j.ajog.2013.03.028. Epub 2013 Mar 25. [PubMed:23535240 ]
Late-onset preeclampsia
  1. Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart DS, Nicolaides K: First-trimester metabolomic detection of late-onset preeclampsia. Am J Obstet Gynecol. 2013 Jan;208(1):58.e1-7. doi: 10.1016/j.ajog.2012.11.003. Epub 2012 Nov 13. [PubMed:23159745 ]
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 ]
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 ]
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 ]
Propionic acidemia
  1. Gronwald W, Klein MS, Kaspar H, Fagerer SR, Nurnberger N, Dettmer K, Bertsch T, Oefner PJ: Urinary metabolite quantification employing 2D NMR spectroscopy. Anal Chem. 2008 Dec 1;80(23):9288-97. doi: 10.1021/ac801627c. [PubMed:19551947 ]
Maple syrup urine disease
  1. Gronwald W, Klein MS, Kaspar H, Fagerer SR, Nurnberger N, Dettmer K, Bertsch T, Oefner PJ: Urinary metabolite quantification employing 2D NMR spectroscopy. Anal Chem. 2008 Dec 1;80(23):9288-97. doi: 10.1021/ac801627c. [PubMed:19551947 ]
Eosinophilic esophagitis
  1. Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work). NA.
Associated OMIM IDs
DrugBank IDDB04151
Phenol Explorer Compound IDNot Available
FooDB IDFDB093588
KNApSAcK IDC00052105
Chemspider ID83153
KEGG Compound IDC01152
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMethylhistidine
METLIN ID3741
PubChem Compound92105
PDB IDNot Available
ChEBI ID50599
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000001
Good Scents IDNot Available
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. Drozak J, Veiga-da-Cunha M, Vertommen D, Stroobant V, Van Schaftingen E: Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J Biol Chem. 2010 Mar 26;285(13):9346-56. doi: 10.1074/jbc.M109.095505. Epub 2010 Jan 22. [PubMed:20097752 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Vranic L, Granic P, Rajic Z: Basic amino acid in the pathogenesis of caries. Acta Stomatol Croat. 1991;25(2):71-6. [PubMed:1819935 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]
  15. Boldyrev AA, Aldini G, Derave W: Physiology and pathophysiology of carnosine. Physiol Rev. 2013 Oct;93(4):1803-45. doi: 10.1152/physrev.00039.2012. [PubMed:24137022 ]
  16. Davydova E, Shimazu T, Schuhmacher MK, Jakobsson ME, Willemen HLDM, Liu T, Moen A, Ho AYY, Malecki J, Schroer L, Pinto R, Suzuki T, Gronsberg IA, Sohtome Y, Akakabe M, Weirich S, Kikuchi M, Olsen JV, Dohmae N, Umehara T, Sodeoka M, Siino V, McDonough MA, Eijkelkamp N, Schofield CJ, Jeltsch A, Shinkai Y, Falnes PO: The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. Nat Commun. 2021 Feb 9;12(1):891. doi: 10.1038/s41467-020-20670-7. [PubMed:33563959 ]
  17. Cross AJ, Major JM, Sinha R: Urinary biomarkers of meat consumption. Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1107-11. doi: 10.1158/1055-9965.EPI-11-0048. Epub 2011 Apr 28. [PubMed:21527577 ]
  18. Mitry P, Wawro N, Rohrmann S, Giesbertz P, Daniel H, Linseisen J: Plasma concentrations of anserine, carnosine and pi-methylhistidine as biomarkers of habitual meat consumption. Eur J Clin Nutr. 2019 May;73(5):692-702. doi: 10.1038/s41430-018-0248-1. Epub 2018 Jul 17. [PubMed:30018457 ]
  19. Chinkes DL: Methods for measuring tissue protein breakdown rate in vivo. Curr Opin Clin Nutr Metab Care. 2005 Sep;8(5):534-7. doi: 10.1097/01.mco.0000170754.25372.37. [PubMed:16079625 ]
  20. Holecek M: Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement. Nutrients. 2020 Mar 22;12(3). pii: nu12030848. doi: 10.3390/nu12030848. [PubMed:32235743 ]
  21. Kwiatkowski S, Seliga AK, Vertommen D, Terreri M, Ishikawa T, Grabowska I, Tiebe M, Teleman AA, Jagielski AK, Veiga-da-Cunha M, Drozak J: SETD3 protein is the actin-specific histidine N-methyltransferase. Elife. 2018 Dec 11;7. pii: 37921. doi: 10.7554/eLife.37921. [PubMed:30526847 ]
  22. Malecki JM, Odonohue MF, Kim Y, Jakobsson ME, Gessa L, Pinto R, Wu J, Davydova E, Moen A, Olsen JV, Thiede B, Gleizes PE, Leidel SA, Falnes PO: Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function. Nucleic Acids Res. 2021 Apr 6;49(6):3185-3203. doi: 10.1093/nar/gkab088. [PubMed:33693809 ]

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 ]
General function:
Involved in methyltransferase activity
Specific function:
Protein-histidine N-methyltransferase that specifically catalyzes 1-methylhistidine (pros-methylhistidine) methylation of target proteins. Mediates methylation of proteins with a His-x-His (HxH) motif (where 'x' is preferably a small amino acid). Catalyzes methylation of target proteins such as S100A9, NDUFB3, SLC39A5, SLC39A7, ARMC6 and DNAJB12; 1-methylhistidine modification may affect the binding of zinc and other metals to its target proteins. Constitutes the main methyltransferase for the 1-methylhistidine modification in cell.
Gene Name:
METTL9
Uniprot ID:
Q9H1A3
Molecular weight:
36.0