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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-29 21:50:44 UTC
HMDB IDHMDB00177
Secondary Accession Numbers
  • HMDB03412
Metabolite Identification
Common NameL-Histidine
DescriptionHistidine is an alpha-amino acid with an imidazole functional group. It is one of the 22 proteinogenic amino acids. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans and other mammals. It was initially thought that it was only essential for infants, but longer-term studies established that it is also essential for adults. Infants four to six months old require 33 mg/kg of histidine. It is not clear how adults make small amounts of histidine, and dietary sources probably account for most of the histidine in the body. Histidine is a precursor for histamine and carnosine biosynthesis. Inborn errors of histidine metabolism exist and are marked by increased histidine levels in the blood. Elevated blood histidine is accompanied by a wide range of symptoms, from mental and physical retardation to poor intellectual functioning, emotional instability, tremor, ataxia and psychosis. Histidine and other imidazole compounds have anti-oxidant, anti-inflammatory and anti-secretory properties (PMID: 9605177 ). The efficacy of L-histidine in protecting inflamed tissue is attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells during acute inflammatory response (PMID: 9605177 ). Histidine, when administered in therapeutic quantities is able to inhibit cytokines and growth factors involved in cell and tissue damage (US patent 6150392). Histidine in medical therapies has its most promising trials in rheumatoid arthritis where up to 4.5 g daily have been used effectively in severely affected patients. Arthritis patients have been found to have low serum histidine levels, apparently because of very rapid removal of histidine from their blood (PMID: 1079527 ). Other patients besides arthritis patients that have been found to be low in serum histidine are those with chronic renal failure. Urinary levels of histidine are reduced in pediatric patients with pneumonia. (PMID: 2084459 ). Asthma patients exhibit increased serum levels of histidine over normal controls (PMID: 23517038 ). Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women (PMID: 23361591 ). Histidine supplementation has been shown to reduce insulin resistance, reduce BMI and fat mass and suppress inflammation and oxidative stress in obese women with metabolic syndrome. Histidine appears to suppress pro-inflammatory cytokine expression, possibly via the NF-κB pathway, in adipocytes (PMID: 23361591 ). Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in chronic kidney disease patients (PMID: 18541578 ). Histidine may have many other possible functions because it is the precursor of the ubiquitous neurohormone-neurotransmitter histamine. Histidine increases histamine in the blood and probably in the brain. Low blood histamine with low serum histidine occurs in rheumatoid arthritis patients. Low blood histamine also occurs in some manic, schizophrenic, high copper and hyperactive groups of psychiatric patients. Histidine is a useful therapy in all patients with low histamine levels. (http://www.dcnutrition.com ).
Structure
Thumb
Synonyms
  1. (S)-1H-Imidazole-4-alanine
  2. (S)-2-Amino-3-(4-imidazolyl)propionsaeure
  3. (S)-4-(2-Amino-2-carboxyethyl)imidazole
  4. (S)-a-Amino-1H-imidazole-4-propanoate
  5. (S)-a-Amino-1H-imidazole-4-propanoic acid
  6. (S)-alpha-Amino-1H-imidazole-4-propanoate
  7. (S)-alpha-Amino-1H-imidazole-4-propanoic acid
  8. (S)-alpha-Amino-1H-imidazole-4-propionate
  9. (S)-alpha-Amino-1H-imidazole-4-propionic acid
  10. (S)-Histidine
  11. (S)1H-Imidazole-4-alanine
  12. 3-(1H-Imidazol-4-yl)-L-Alanine
  13. Amino-1H-imidazole-4-propanoate
  14. Amino-1H-imidazole-4-propanoic acid
  15. Amino-4-imidazoleproprionate
  16. Amino-4-imidazoleproprionic acid
  17. Glyoxaline-5-alanine
  18. His
  19. Histidine
  20. L-(-)-Histidine
Chemical FormulaC6H9N3O2
Average Molecular Weight155.1546
Monoisotopic Molecular Weight155.069476547
IUPAC Name(2S)-2-amino-3-(1H-imidazol-4-yl)propanoic acid
Traditional Namehistidine
CAS Registry Number71-00-1
SMILES
N[C@@H](CC1=CNC=N1)C(O)=O
InChI Identifier
InChI=1S/C6H9N3O2/c7-5(6(10)11)1-4-2-8-3-9-4/h2-3,5H,1,7H2,(H,8,9)(H,10,11)/t5-/m0/s1
InChI KeyHNDVDQJCIGZPNO-YFKPBYRVSA-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
  • alpha-amino acid(ChEBI)
  • imidazoles(ChEBI)
Substituents
  • Aminoimidazole
  • Carboxylic Acid
  • Imidazole
  • Imidazolyl Carboxylic Acid Derivative
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Food
Biofunction
  • Component of Aminoacyl-tRNA biosynthesis
  • Component of Histidine metabolism
  • Component of Nitrogen metabolism
  • Essential amino acid
  • Essential amino acids
  • semi-essential amino acids
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point287 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility45.6 mg/mLNot Available
LogP-3.32CHMELIK,J ET AL. (1991)
Predicted Properties
PropertyValueSource
Water Solubility71.3 g/LALOGPS
logP-2.7ALOGPS
logP-3.3ChemAxon
logS-0.34ALOGPS
pKa (Strongest Acidic)1.85ChemAxon
pKa (Strongest Basic)9.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity37.49ChemAxon
Polarizability14.92ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • All Tissues
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Ammonia RecyclingSMP00009map00910
Histidine MetabolismSMP00044map00340
Transcription/TranslationSMP00019Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified75.0 +/- 20.0 uMNewborn (0-30 days old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified86.0 +/- 10.0 uMChildren (1-13 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified89.0 +/- 11.0 uMAdult (>18 years old)MaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified83.0 +/- 14.0 uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified143.1 +/- 27.3 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified88.00 (56.00-120.00) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified82.0 (72.0-92.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified131.2 +/- 37.3 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified14.0 +/- 8.0 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified20.7 +/- 7.5 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified16.8 +/- 2.7 uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified18.6 +/- 3.3 uMAdult (>18 years old)FemaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified16.4 +/- 6.1 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified13.00 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified10.9 (10.4-11.4) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified11.9 +/- 1.7 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
SalivaDetected and Quantified24.99 +/- 12.94 uMAdult (>18 years old)FemaleNormal details
SalivaDetected and Quantified6.02 +/- 4.39 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
SalivaDetected and Quantified9.93 +/- 9.50 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified<0.25 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified<0.25 uMAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified9.4 +/- 4.9 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified18.67 +/- 10.20 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
SalivaDetected and Quantified8.2 +/- 1.2 uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified>10 uMAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)MaleNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified101.9 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified25.79-212.81 umol/mmol creatinineAdult (>18 years old)BothNormal
    • David F. Putnam C...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified87.2 (23.0-151.0) umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified47.12 umol/mmol creatinineAdult (>18 years old)MaleNormal
      • Shaykhutdinov RA,...
    details
    UrineDetected and Quantified0.0036 - 0.0376 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified43 (17-90) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified2.2 (1.18-3.4) umol/mmol creatinineNewborn (0-30 days old)BothNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified31.0 +/- 15.0 umol/mmol creatinineChildren (1-13 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified85.0 +/- 33.0 umol/mmol creatinineAdult (>18 years old)MaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified62.0 +/- 28.0 umol/mmol creatinineAdult (>18 years old)FemaleNormal
      • Geigy Scientific ...
      • West Cadwell, N.J...
      • Basel, Switzerlan...
    details
    UrineDetected and Quantified60.75 +/- 27.45 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified45.6 (21.7-71.5) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified88 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified194.90 +/- 144.31 umol/mmol creatinineInfant (0-1 year old)BothNormal details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified46.1 +/- 17.5 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
    BloodDetected and Quantified885.00 (290.00-1420.00) uMChildren (1-13 years old)BothHistidinemia details
    BloodDetected and Quantified116.68 +/- 18.15 uMElderly (>65 years old)BothAlzheimer's disease details
    BloodDetected and Quantified67.0 (64.0-70.0) uMAdult (>18 years old)BothDengue fever details
    BloodDetected and Quantified80.5 +/- 4.2 uMAdult (>18 years old)Both
    Epilepsy
    details
    BloodDetected and Quantified107.0 +/- 6.5 uMAdult (>18 years old)Both
    Epilepsy
    details
    Cerebrospinal Fluid (CSF)Detected and Quantified21.4 +/- 6.6 uMChildren (1-13 years old)Not SpecifiedLeukemia details
    Cerebrospinal Fluid (CSF)Detected and Quantified10.3 +/- 3.7 uMChildren (1-13 years old)Not Specified
    Leukemia
    details
    Cerebrospinal Fluid (CSF)Detected and Quantified95.00 (48.00-142.00) uMChildren (1-13 years old)BothHistidinemia details
    Cerebrospinal Fluid (CSF)Detected and Quantified130.0 uMAdult (>18 years old)BothHistidinemia details
    Cerebrospinal Fluid (CSF)Detected and Quantified14.4 +/- 6.32 uMAdult (>18 years old)BothProgressive dementia details
    SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothOral cancer details
    SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)FemaleBreast cancer details
    SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPancreatic cancer details
    SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedPeriodontal diseases details
    SalivaDetected and Quantified16.96 +/- 7.43 uMAdult (>18 years old)MaleAlzheimer's disease details
    SalivaDetected and Quantified23.31 +/- 8.62 uMAdult (>18 years old)MaleFrontotemporal lobe dementia details
    SalivaDetected and Quantified17.50 +/- 4.53 uMAdult (>18 years old)BothLewy body disease details
    UrineDetected and Quantified0.0033 - 0.0186 umol/mmol creatinineAdult (>18 years old)BothADPKD details
    UrineDetected and Quantified30.5 +/- 4.3 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
    UrineDetected and Quantified1696.84 (339.37-3054.30) umol/mmol creatinineChildren (1-13 years old)BothHistidinuria details
    UrineDetected and Quantified105.3 +/- 12.7 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
    UrineDetected and Quantified65.5 +/- 11.3 umol/mmol creatinineAdult (>18 years old)Both3-Hydroxy-3- methylglutaryl-CoA lyase (HL) deficency details
    UrineDetected and Quantified52.9 +/- 12.5 umol/mmol creatinineAdult (>18 years old)BothArgininosuccinic aciduria (ASL) details
    UrineDetected and Quantified154.3 +/- 13.7 umol/mmol creatinineAdult (>18 years old)BothPropionic acidemia details
    UrineDetected and Quantified52 +/- 29 umol/mmol creatinineAdult (>18 years old)BothTyrosinemia I details
    UrineDetected and Quantified37.9 +/- 9.8 umol/mmol creatinineAdult (>18 years old)BothTyrosinemia I details
    UrineDetected and Quantified62.6 +/- 12.3 umol/mmol creatinineAdult (>18 years old)BothPhenylketonuria details
    UrineDetected and Quantified68 +/- 19.9 umol/mmol creatinineAdult (>18 years old)BothPhenylketonuria details
    UrineDetected and Quantified171.8 +/- 4.3 umol/mmol creatinineAdult (>18 years old)BothMaple syrup urine disease details
    UrineDetected and Quantified180.1 +/- 12.4 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
    Dengue fever
    1. Klassen P, Furst P, Schulz C, Mazariegos M, Solomons NW: Plasma free amino acid concentrations in healthy Guatemalan adults and in patients with classic dengue. Am J Clin Nutr. 2001 Mar;73(3):647-52. Pubmed: 11237944
    Epilepsy
    1. Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. Pubmed: 14992292
    Histidinemia
    1. Wevers RA, Engelke U, Wendel U, de Jong JG, Gabreels FJ, Heerschap A: Standardized method for high-resolution 1H-NMR of cerebrospinal fluid. Clin Chem. 1995 May;41(5):744-51. Pubmed: 7729054
    2. MetaGene
    3. MetaGene
    Leukemia
    1. Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    Associated OMIM IDs
    DrugBank IDDB00117
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB011856
    KNApSAcK IDC00001363
    Chemspider ID6038
    KEGG Compound IDC00135
    BioCyc IDHIS
    BiGG ID33985
    Wikipedia LinkL-Histidine
    NuGOwiki LinkHMDB00177
    Metagene LinkHMDB00177
    METLIN ID21
    PubChem Compound6274
    PDB ID1KAH
    ChEBI ID15971
    References
    Synthesis ReferenceAurelio Luigi; Brownlee Robert T C; Hughes Andrew B A novel synthesis of N-methyl asparagine, arginine, histidine, and tryptophan. Organic letters (2002), 4(21), 3767-9.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR: Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. Pubmed: 15933069
    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. Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. Pubmed: 2026685
    4. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. Pubmed: 12097436
    5. Nicholson JK, O'Flynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH: Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984 Jan 15;217(2):365-75. Pubmed: 6696735
    6. Wevers RA, Engelke U, Wendel U, de Jong JG, Gabreels FJ, Heerschap A: Standardized method for high-resolution 1H-NMR of cerebrospinal fluid. Clin Chem. 1995 May;41(5):744-51. Pubmed: 7729054
    7. Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA: Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem. 1984 Mar;42(3):833-7. Pubmed: 6198473
    8. Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    9. Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. Pubmed: 12297216
    10. Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. Pubmed: 14992292
    11. Klassen P, Furst P, Schulz C, Mazariegos M, Solomons NW: Plasma free amino acid concentrations in healthy Guatemalan adults and in patients with classic dengue. Am J Clin Nutr. 2001 Mar;73(3):647-52. Pubmed: 11237944
    12. Mukerji SK, Pimstone NR, Gandhi SN, Tan KT: Biochemical diagnosis and monitoring therapeutic modulation of disease activity in an unusual case of congenital erythropoietic porphyria. Clin Chem. 1985 Dec;31(12):1946-51. Pubmed: 4064282
    13. Churchill D, Yacoub JM, Siu KP, Symes A, Gault MH: Toxic nephropathy after low-dose methoxyflurane anesthesia: drug interaction with secobarbital? Can Med Assoc J. 1976 Feb 21;114(4):326-8, 333. Pubmed: 1253070
    14. Sieja K, Stanosz S, von Mach-Szczypinski J, Olewniczak S, Stanosz M: Concentration of histamine in serum and tissues of the primary ductal breast cancers in women. Breast. 2005 Jun;14(3):236-41. Epub 2005 Jan 21. Pubmed: 15927833
    15. Masini E, Fabbroni V, Giannini L, Vannacci A, Messerini L, Perna F, Cortesini C, Cianchi F: Histamine and histidine decarboxylase up-regulation in colorectal cancer: correlation with tumor stage. Inflamm Res. 2005 Apr;54 Suppl 1:S80-1. Pubmed: 15928846
    16. Xiao YP, Han CB, Mao XY, Li JY, Xu L, Ren CS, Xin Y: Relationship between abnormality of FHIT gene and EBV infection in gastric cancer. World J Gastroenterol. 2005 Jun 7;11(21):3212-6. Pubmed: 15929169
    17. Mason AB, Halbrooks PJ, James NG, Connolly SA, Larouche JR, Smith VC, MacGillivray RT, Chasteen ND: Mutational analysis of C-lobe ligands of human serum transferrin: insights into the mechanism of iron release. Biochemistry. 2005 Jun 7;44(22):8013-21. Pubmed: 15924420
    18. Janknecht R, Hipskind RA, Houthaeve T, Nordheim A, Stunnenberg HG: Identification of multiple SRF N-terminal phosphorylation sites affecting DNA binding properties. EMBO J. 1992 Mar;11(3):1045-54. Pubmed: 1547771
    19. Peterson JW, Boldogh I, Popov VL, Saini SS, Chopra AK: Anti-inflammatory and antisecretory potential of histidine in Salmonella-challenged mouse small intestine. Lab Invest. 1998 May;78(5):523-34. Pubmed: 9605177
    20. Gerber DA: Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity. J Clin Invest. 1975 Jun;55(6):1164-73. Pubmed: 1079527
    21. Hemler RJ, Hoogeveen JH, Kraaier V, Van Huffelen AC, Wieneke GH, Hijman R, Glerum JH: A pharmacological model of cerebral ischemia. The effects of indomethacin on cerebral blood flow velocity, quantitative EEG and cognitive functions. Methods Find Exp Clin Pharmacol. 1990 Nov;12(9):641-3. Pubmed: 2084459
    22. Feng RN, Niu YC, Sun XW, Li Q, Zhao C, Wang C, Guo FC, Sun CH, Li Y: Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2013 May;56(5):985-94. doi: 10.1007/s00125-013-2839-7. Epub 2013 Jan 30. Pubmed: 23361591
    23. Watanabe M, Suliman ME, Qureshi AR, Garcia-Lopez E, Barany P, Heimburger O, Stenvinkel P, Lindholm B: Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality. Am J Clin Nutr. 2008 Jun;87(6):1860-6. Pubmed: 18541578
    24. Jung J, Kim SH, Lee HS, Choi GS, Jung YS, Ryu DH, Park HS, Hwang GS: Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin Exp Allergy. 2013 Apr;43(4):425-33. doi: 10.1111/cea.12089. Pubmed: 23517038
    25. Effective method for the amelioration and prevention of tissue and cellular damage

    Enzymes

    General function:
    Involved in carboxy-lyase activity
    Specific function:
    Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
    Gene Name:
    DDC
    Uniprot ID:
    P20711
    Molecular weight:
    53893.755
    Reactions
    L-Histidine → Histamine + Carbon dioxidedetails
    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 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
    General function:
    Involved in nucleotide binding
    Specific function:
    Not Available
    Gene Name:
    HARS2
    Uniprot ID:
    P49590
    Molecular weight:
    56887.865
    Reactions
    Adenosine triphosphate + L-Histidine + tRNA(His) → Adenosine monophosphate + Pyrophosphate + L-histidyl-tRNA(His)details
    Adenosine triphosphate + L-Histidine + tRNA(His) → Adenosine monophosphate + Pyrophosphate + L-Histidyl-tRNA(His)details
    General function:
    Involved in nucleotide binding
    Specific function:
    Not Available
    Gene Name:
    HARS
    Uniprot ID:
    P12081
    Molecular weight:
    52719.54
    Reactions
    Adenosine triphosphate + L-Histidine + tRNA(His) → Adenosine monophosphate + Pyrophosphate + L-histidyl-tRNA(His)details
    Adenosine triphosphate + L-Histidine + tRNA(His) → Adenosine monophosphate + Pyrophosphate + L-Histidyl-tRNA(His)details
    References
    1. Nagatoyo Y, Iwaki J, Suzuki S, Kuno A, Hasegawa T: Molecular recognition of histidine tRNA by histidyl-tRNA synthetase from hyperthermophilic archaeon, Aeropyrum pernix K1. Nucleic Acids Symp Ser (Oxf). 2005;(49):307-8. Pubmed: 17150756
    2. Rosen AE, Brooks BS, Guth E, Francklyn CS, Musier-Forsyth K: Evolutionary conservation of a functionally important backbone phosphate group critical for aminoacylation of histidine tRNAs. RNA. 2006 Jul;12(7):1315-22. Epub 2006 Jun 1. Pubmed: 16741232
    General function:
    Involved in histidine ammonia-lyase activity
    Specific function:
    Not Available
    Gene Name:
    HAL
    Uniprot ID:
    P42357
    Molecular weight:
    49122.09
    Reactions
    L-Histidine → Urocanic acid + Ammoniadetails
    References
    1. Viergutz S, Retey J: Kinetic analysis of the reactions catalyzed by histidine and phenylalanine ammonia lyases. Chem Biodivers. 2004 Feb;1(2):296-302. Pubmed: 17191848
    2. Lambrecht NW, Yakubov I, Sachs G: Fasting-induced changes in ECL cell gene expression. Physiol Genomics. 2007 Oct 22;31(2):183-92. Epub 2007 May 29. Pubmed: 17536021
    3. Watts KT, Mijts BN, Lee PC, Manning AJ, Schmidt-Dannert C: Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family. Chem Biol. 2006 Dec;13(12):1317-26. Pubmed: 17185227
    4. Katona A, Tosa MI, Paizs C, Retey J: Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates. Chem Biodivers. 2006 May;3(5):502-8. Pubmed: 17193285
    General function:
    Involved in carboxy-lyase activity
    Specific function:
    Catalyzes the biosynthesis of histamine from histidine.
    Gene Name:
    HDC
    Uniprot ID:
    P19113
    Molecular weight:
    74139.825
    Reactions
    L-Histidine → Histamine + CO(2)details
    L-Histidine → Histamine + Carbon dioxidedetails
    References
    1. Landete JM, Pardo I, Ferrer S: Histamine, histidine, and growth-phase mediated regulation of the histidine decarboxylase gene in lactic acid bacteria isolated from wine. FEMS Microbiol Lett. 2006 Jul;260(1):84-90. Pubmed: 16790022
    2. Fernandez M, del Rio B, Linares DM, Martin MC, Alvarez MA: Real-time polymerase chain reaction for quantitative detection of histamine-producing bacteria: use in cheese production. J Dairy Sci. 2006 Oct;89(10):3763-9. Pubmed: 16960050
    3. Nitta Y, Kikuzaki H, Ueno H: Food components inhibiting recombinant human histidine decarboxylase activity. J Agric Food Chem. 2007 Jan 24;55(2):299-304. Pubmed: 17227057
    4. Kitamura Y, Das AK, Murata Y, Maeyama K, Dev S, Wakayama Y, Kalubi B, Takeda N, Fukui H: Dexamethasone suppresses histamine synthesis by repressing both transcription and activity of HDC in allergic rats. Allergol Int. 2006 Sep;55(3):279-86. Pubmed: 17075268
    5. Castellani ML, Kempuraj D, Frydas S, Theoharides TC, Simeonidou I, Conti P, Vecchiet J: Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Neuroimmunomodulation. 2006;13(3):179-86. Epub 2006 Dec 21. Pubmed: 17191019
    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 + L-Histidine + Beta-Alanine → ADP + Phosphoric acid + Carnosinedetails
    Adenosine triphosphate + L-Histidine + Beta-Alanine → Adenosine monophosphate + Pyrophosphate + Carnosinedetails
    Adenosine triphosphate + L-Histidine + Gamma-Aminobutyric acid → Adenosine monophosphate + Pyrophosphate + Homocarnosinedetails
    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

    Transporters

    General function:
    Amino acid transport and metabolism
    Specific function:
    Sodium-dependent amino acid/proton antiporter. Mediates electrogenic cotransport of glutamine and sodium ions in exchange for protons. Also recognizes histidine, asparagine and alanine. May mediate amino acid transport in either direction under physiological conditions. May play a role in nitrogen metabolism and synaptic transmission
    Gene Name:
    SLC38A3
    Uniprot ID:
    Q99624
    Molecular weight:
    55772.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
    3. Eppig JJ, Pendola FL, Wigglesworth K, Pendola JK: Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod. 2005 Aug;73(2):351-7. Epub 2005 Apr 20. Pubmed: 15843493
    General function:
    Involved in transmembrane transport
    Specific function:
    Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells
    Gene Name:
    SLC16A10
    Uniprot ID:
    Q8TF71
    Molecular weight:
    55492.1
    References
    1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed: 11278508
    2. Kim DK, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H: The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics. 2002 Jan;79(1):95-103. Pubmed: 11827462