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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-09 18:43:34 UTC
HMDB IDHMDB00479
Secondary Accession NumbersNone
Metabolite Identification
Common Name3-Methylhistidine
Description3-Methylhistidine is a product of peptide bond synthesis and methylation of actin and myosin. The measurement of 3-Methylhistidine provides an index of the rate of muscle protein breakdown.
Structure
Thumb
Synonyms
  1. (2S)-2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoate
  2. (2S)-2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acid
  3. 3-Methyl-L-histidine
  4. 3-Methylhistidine
  5. 3-N-Methyl-L-histidine
  6. L-3-Methylhistidine
  7. N(Pai)-Methyl-L-histidine
  8. N(Pi)-methyl-L-histidine
  9. N(Pros)-methyl-L-histidine
  10. N3-Methyl-L-histidine
  11. Pi-Methyl-L-histidine
  12. Tau-Methyl-L-histidine
  13. Tau-methylhistidine
Chemical FormulaC7H11N3O2
Average Molecular Weight169.1811
Monoisotopic Molecular Weight169.085126611
IUPAC Name(2S)-2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acid
Traditional Name3-methylhistidine
CAS Registry Number368-16-1
SMILES
CN1C=NC=C1C[C@H](N)C(O)=O
InChI Identifier
InChI=1S/C7H11N3O2/c1-10-4-9-3-5(10)2-6(8)7(11)12/h3-4,6H,2,8H2,1H3,(H,11,12)/t6-/m0/s1
InChI KeyJDHILDINMRGULE-LURJTMIESA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aromatic Heteromonocyclic Compounds
Substituents
  • Aminoimidazole
  • Carboxylic Acid
  • Imidazole
  • Imidazolyl Carboxylic Acid Derivative
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility200 mg/mL at 25 °CBEILSTEIN
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.93 g/LALOGPS
logP-2.9ALOGPS
logP-3.4ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)1.96ChemAxon
pKa (Strongest Basic)9.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area81.14ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity42.96ChemAxon
Polarizability16.58ChemAxon
Spectra
SpectraMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Muscle
  • Prostate
  • Skeletal Muscle
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified2.7 (0.0-5.9) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified3.0 (2.7 - 5.9) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified3.82 +/- 2.43 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified27.68 +/- 28.12 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
UrineDetected and Quantified5.26 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified69.27 umol/mmol creatinineAdult (>18 years old)Male
Normal
    • Shaykhutdinov RA,...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified16.5 (2.8-59.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified12.5 +/- 4.2 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified42.76 +/- 22.84 umol/mmol creatinineInfant (0-1 year old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified13.0 +/- 10.4 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified23.7 +/- 18.6 uMAdult (>18 years old)Both
Kidney disease
details
BloodDetected and Quantified5.16 +/- 1.27 uMElderly (>65 years old)BothAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified2.48 +/- 1.58 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
UrineDetected and Quantified24.0 +/- 1.7 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
UrineDetected and Quantified11.6 +/- 6.6 umol/mmol creatinineAdult (>18 years old)Not SpecifiedDiabetes mellitus details
UrineDetected and Quantified16.0 +/- 9.0 umol/mmol creatinineAdult (>18 years old)Not SpecifiedObesity details
UrineDetected and Quantified44.5 +/- 1.3 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia 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 IDFDB021798
KNApSAcK IDNot Available
Chemspider ID58494
KEGG Compound IDC01152
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00479
Metagene LinkHMDB00479
METLIN ID5466
PubChem Compound64969
PDB IDMHS
ChEBI ID27596
References
Synthesis ReferenceOhba, Masashi; Mukaihira, Takafumi; Fujii, Tozo. Preparatory study for the synthesis of the starfish alkaloid imbricatine. Syntheses of 5-arylthio-3-methyl-L-histidines. Chemical & Pharmaceutical Bulletin (1994), 42(9), 1784-90.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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
  2. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  3. Bucciante G, Mencini A, Boninsegna A, Branca D, Scutari A, Scutari G: 3-Methylhistidine urinary excretion as an index of skeletal muscle protein metabolism: reference values. G Clin Med. 1985 Nov-Dec;66(11-12):451-8. Pubmed: 3835089
  4. Schmitz JE: [Effect of metabolism-oriented substrate administration on energy and protein metabolism in polytraumatized artificial respiration patients] Infusionsther Klin Ernahr. 1984 Aug;11(4):205-18. Pubmed: 6434422
  5. McKeran RO, Halliday D, Purkiss P: Comparison of human myofibrillar protein catabolic rate derived from 3-methylhistidine excretion with synthetic rate from muscle biopsies during L-[alpha-15N]lysine infusion. Clin Sci Mol Med. 1978 May;54(5):471-5. Pubmed: 750147
  6. Teahon K, Rideout JM: A sensitive and specific high performance liquid chromatographic assay for imidazole dipeptides and 3-methylhistidine in human muscle biopsies, serum and urine. Biomed Chromatogr. 1992 Jan-Feb;6(1):16-9. Pubmed: 1600369
  7. Adlerberth A, Jagenburg R, Lindstedt G, Stenstrom G, Hasselgren PO: Effects of thyroid hormone and beta-adrenoceptor blocking agents on urinary excretion of 3-methylhistidine and plasma amino acids in man. Eur J Clin Invest. 1986 Aug;16(4):316-20. Pubmed: 3093243
  8. Wang Z, Deurenberg P, Matthews DE, Heymsfield SB: Urinary 3-methylhistidine excretion: association with total body skeletal muscle mass by computerized axial tomography. JPEN J Parenter Enteral Nutr. 1998 Mar-Apr;22(2):82-6. Pubmed: 9527964
  9. Nygren J, Thorell A, Brismar K, Essen P, Wernerman J, McNurlan MA, Garlick PJ, Ljungqvist O: Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged. Clin Sci (Lond). 2002 Apr;102(4):457-64. Pubmed: 11914108
  10. Elia M, Carter A, Bacon S, Winearls CG, Smith R: Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown. Br Med J (Clin Res Ed). 1981 Jan 31;282(6261):351-4. Pubmed: 6780020
  11. Rathmacher JA, Flakoll PJ, Nissen SL: A compartmental model of 3-methylhistidine metabolism in humans. Am J Physiol. 1995 Jul;269(1 Pt 1):E193-8. Pubmed: 7631776
  12. Lunyong VE, Friedman Z: Myofibrillar protein degradation in premature infants with respiratory distress as assessed by 3-methylhistidine and creatinine excretions. Am J Clin Nutr. 1982 Sep;36(3):485-91. Pubmed: 7113954
  13. Buchholz-Wimmer GB, Wimmer W, Herbertz L, Reinauer H: [3-Methylhistidine as a parameter for the determination of muscle proteolysis in the post-stress syndrome and in diabetes mellitus] Infusionsther Klin Ernahr. 1984 Jun;11(3):168-74. Pubmed: 6434416
  14. Vesali RF, Klaude M, Thunblad L, Rooyackers OE, Wernerman J: Contractile protein breakdown in human leg skeletal muscle as estimated by [2H3]-3-methylhistidine: a new method. Metabolism. 2004 Aug;53(8):1076-80. Pubmed: 15281022
  15. Bird SP, Tarpenning KM, Marino FE: Independent and combined effects of liquid carbohydrate/essential amino acid ingestion on hormonal and muscular adaptations following resistance training in untrained men. Eur J Appl Physiol. 2006 May;97(2):225-38. Epub 2006 Mar 24. Pubmed: 16456674
  16. Lamisse F, May MA, Couet C, Constans T, Bacq Y, Delarue J, Lamagnere JP, Colombat P, Garrigue MA: [Changes in nutritional status at the initial phase of treatment of cancers and malignant hemopathies] Rev Med Interne. 1987 May-Jun;8(3):257-61. Pubmed: 3616232
  17. Neuhauser M, Bergstrom J, Chao L, Holmstrom J, Nordlund L, Vinnars E, Furst P: Urinary excretion of 3-methylhistidine as an index of muscle protein catabolism in postoperative trauma: the effect of parenteral nutrition. Metabolism. 1980 Dec;29(12):1206-13. Pubmed: 6779092
  18. Emery PW, Rennie MJ: Elimination by formaldehyde of interference with 3-methylhistidine determination: application of the method to the study of muscle protein degradation. Anal Biochem. 1982 Oct;126(1):67-73. Pubmed: 7181118
  19. Tomas FM, Ballard FJ, Pope LM: Age-dependent changes in the rate of myofibrillar protein degradation in humans as assessed by 3-methylhistidine and creatinine excretion. Clin Sci (Lond). 1979 Apr;56(4):341-6. Pubmed: 477219
  20. Long CL, Dillard DR, Bodzin JH, Geiger JW, Blakemore WS: Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans. Metabolism. 1988 Sep;37(9):844-9. Pubmed: 3138511
  21. Young VR, Munro HN: Ntau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc. 1978 Jul;37(9):2291-300. Pubmed: 350635

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
General function:
Involved in catalytic activity
Specific function:
Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine.
Gene Name:
CARNS1
Uniprot ID:
A5YM72
Molecular weight:
101318.725
Reactions
Adenosine triphosphate + 3-Methylhistidine + Beta-Alanine → Adenosine monophosphate + Pyrophosphate + Anserinedetails
General function:
Not Available
Specific function:
N5-glutamine methyltransferase responsible for the methylation of the GGQ triplet of the mitochondrial translation release factor MTRF1L.
Gene Name:
HEMK1
Uniprot ID:
Q9Y5R4
Molecular weight:
Not Available
Reactions
L-Histidine + S-Adenosylmethionine → 3-Methylhistidine + S-Adenosylhomocysteinedetails
General function:
Not Available
Specific function:
Probable methyltransferase (By similarity).
Gene Name:
METTL2B
Uniprot ID:
Q6P1Q9
Molecular weight:
Not Available
Reactions
L-Histidine + S-Adenosylmethionine → 3-Methylhistidine + S-Adenosylhomocysteinedetails
General function:
Not Available
Specific function:
Probable methyltransferase (By similarity).
Gene Name:
METTL6
Uniprot ID:
Q8TCB7
Molecular weight:
Not Available
Reactions
L-Histidine + S-Adenosylmethionine → 3-Methylhistidine + S-Adenosylhomocysteinedetails
General function:
Not Available
Specific function:
Methyltransferase that may act on DNA.
Gene Name:
WBSCR22
Uniprot ID:
O43709
Molecular weight:
Not Available
Reactions
L-Histidine + S-Adenosylmethionine → 3-Methylhistidine + S-Adenosylhomocysteinedetails