L-Histidine (T3D4363)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2014-08-29 06:34:56 UTC
Update Date2014-12-24 20:26:47 UTC
Accession NumberT3D4363
Identification
Common NameL-Histidine
ClassSmall Molecule
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 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 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 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. Asthma patients exhibit increased serum levels of histidine over normal controls Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women 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-kappaB pathway, in adipocytes Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in chronic kidney disease patients 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.
Compound Type
  • Amine
  • Animal Toxin
  • Conditionally Essential Amino Acid
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(S)-1H-Imidazole-4-alanine
(S)-2-Amino-3-(4-imidazolyl)propionsaeure
(S)-4-(2-Amino-2-carboxyethyl)imidazole
(S)-a-Amino-1H-imidazole-4-propanoate
(S)-a-Amino-1H-imidazole-4-propanoic acid
(S)-alpha-Amino-1H-imidazole-4-propanoate
(S)-alpha-Amino-1H-imidazole-4-propanoic acid
(S)-alpha-Amino-1H-imidazole-4-propionate
(S)-alpha-Amino-1H-imidazole-4-propionic acid
(S)-Histidine
(S)-α-amino-1H-Imidazole-4-propanoic acid
(S)1H-Imidazole-4-alanine
3-(1H-Imidazol-4-yl)-L-Alanine
Amino-1H-imidazole-4-propanoate
Amino-1H-imidazole-4-propanoic acid
Amino-4-imidazoleproprionate
Amino-4-imidazoleproprionic acid
Glyoxaline-5-alanine
H
His
Histidine
L-(-)-Histidine
L-(−)-histidine
L-Histidin
Chemical FormulaC6H9N3O2
Average Molecular Mass155.155 g/mol
Monoisotopic Mass155.069 g/mol
CAS Registry Number71-00-1
IUPAC Name(2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid
Traditional NameL-histidine
SMILES[H][C@](N)(CC1=CN=CN1)C(O)=O
InChI IdentifierInChI=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 KeyInChIKey=HNDVDQJCIGZPNO-YFKPBYRVSA-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
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Amino acid
  • Carboxylic acid
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen 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
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • All Tissues
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Ammonia RecyclingSMP00009 map00910
Histidine MetabolismSMP00044 map00340
Transcription/TranslationSMP00019 Not Available
Hartnup DisorderSMP00189 Not Available
HistidinemiaSMP00191 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point287 dec°C
Boiling PointNot Available
Solubility4.56E+004 mg/L (at 25°C)
LogP-3.32
Predicted Properties
PropertyValueSource
Water Solubility71.3 g/LALOGPS
logP-2.7ALOGPS
logP-3.6ChemAxon
logS-0.34ALOGPS
pKa (Strongest Acidic)1.85ChemAxon
pKa (Strongest Basic)9.44ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity38.06 m³·mol⁻¹ChemAxon
Polarizability14.67 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0udi-0940000000-43b9b035189af65e19cb2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0udi-0910000000-fc3ecec9d4ff3aa8cb092014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0udi-0910000000-8284a673a35f7ac2241f2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0fk9-8910000000-a3231b1a418b5798ecac2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0udi-1920000000-227e8116769731104e822014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-0ufu-2942100000-31605fd50ecc1f5be0ed2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0940000000-43b9b035189af65e19cb2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0910000000-fc3ecec9d4ff3aa8cb092017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0910000000-8284a673a35f7ac2241f2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-QQ (Non-derivatized)splash10-0002-2901100000-ae0f3865934743de764c2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0fk9-8910000000-a3231b1a418b5798ecac2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0udi-1920000000-227e8116769731104e822017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0ufu-2942100000-31605fd50ecc1f5be0ed2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0ue9-0900000000-75e38a3f347210c301b02017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0udi-0910000000-c54bd92cc112eec7e5092017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9500000000-1d29684ccb63836878652016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-03di-6900000000-1dd400a16b8067f4daea2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0a4i-0900000000-21530fac9975dc1edc7c2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-053r-9300000000-a946c375931adb366aae2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-053r-9000000000-61a3602d80bc0d54c5792012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-7d63b501889c2628f4f02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-001i-0900000000-d4ccd4e44ca818b4cb172012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-811aee5724fe0999c1342012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-2900000000-052753eb699ae7cb4cb92012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-3e145a05e6a71a0a2f562012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-143a4b9d88183bc5abe72012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-03di-0900000000-a8c213472da676a241f22012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-001i-0900000000-dfdf9562f155abb5fdeb2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0uk9-0879331100-8434b5b9e7e5700c23532012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-000i-0900000000-aaaaadcecd4cd7c94e1e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0udi-0900000000-90c4cbd09d7abc0030132012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0udi-0900000000-1381708d18c24486773d2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0w29-0696321100-eb62fc608270d11517072012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-000i-0900000000-3450566ff38e6506a70f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-01q9-7900000000-124509a66476629ce10a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0udi-0900000000-efa6a21b1be16fda08022012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0udi-0900000000-137840e69da48c6114e42012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0udu-3900000000-06d50e90c797793a72d72012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0006-9100000000-de7c9eb8068ef4f39f852012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-00l6-9000000000-ebf778679d4c6d6a60572012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-014i-9000000000-08d0188684283d1b23722012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-0a4i-0900000000-46c2f608d27f0381a0392012-08-31View Spectrum
MSMass Spectrum (Electron Ionization)splash10-001i-9100000000-ae0a0b81669663b3b4a52018-05-25View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureAbsorbed from the small intestine via an active transport mechanism requiring the presence of sodium.
Mechanism of ToxicitySince the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints.
L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis.
This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.
MetabolismNot Available
Toxicity ValuesORL-RAT LD50 > 15000 mg/kg, IPR-RAT LD50 > 8000 mg/kg, ORL-MUS LD50 > 15000 mg/kg, IVN-MUS LD50 > 2000 mg/kg
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThe actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00117
HMDB IDHMDB00177
PubChem Compound ID6274
ChEMBL IDCHEMBL17962
ChemSpider ID6038
KEGG IDC00135
UniProt IDNot Available
OMIM ID
ChEBI ID15971
BioCyc IDHIS
CTD IDNot Available
Stitch IDNot Available
PDB IDHIS
ACToR IDNot Available
Wikipedia LinkL-Histidine
References
Synthesis Reference

Kazumi Araki, Tetsuro Kuga, “Process for producing L-histidine by fermentation.” U.S. Patent US4495283, issued April, 1975.

MSDSLink
General References
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  12. 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. [1253070 ]
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  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. [15927833 ]
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  20. 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. [15929169 ]
  21. 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. [15924420 ]
  22. 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. [1547771 ]
  23. 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. [6198473 ]
  24. 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. doi: 10.1038/nature07762. [19212411 ]
  25. Effective method for the amelioration and prevention of tissue and cellular damage [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histidine decarboxylase
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the biosynthesis of histamine from histidine.
Gene Name:
HDC
Uniprot ID:
P19113
Molecular Weight:
74139.825 Da
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. [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. [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. [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. [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. [17191019 ]
Target Details
2. Histidine ammonia-lyase
General Function:
Histidine ammonia-lyase activity
Specific Function:
Not Available
Gene Name:
HAL
Uniprot ID:
P42357
Molecular Weight:
72696.9 Da
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. [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. [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. [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. [17193285 ]
Target Details
3. Sodium-coupled neutral amino acid transporter 3
General Function:
Symporter activity
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:
55772.405 Da
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. [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. [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. [15843493 ]
Target Details
4. Histidine--tRNA ligase, cytoplasmic
General Function:
Histidine-trna ligase activity
Specific Function:
Not Available
Gene Name:
HARS
Uniprot ID:
P12081
Molecular Weight:
57409.97 Da
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. [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. [16741232 ]
Target Details
5. Glutaminyl-peptide cyclotransferase
General Function:
Zinc ion binding
Specific Function:
Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides.
Gene Name:
QPCT
Uniprot ID:
Q16769
Molecular Weight:
40876.14 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory4400 uMNot AvailableBindingDB 7953
References
  1. Schilling S, Niestroj AJ, Rahfeld JU, Hoffmann T, Wermann M, Zunkel K, Wasternack C, Demuth HU: Identification of human glutaminyl cyclase as a metalloenzyme. Potent inhibition by imidazole derivatives and heterocyclic chelators. J Biol Chem. 2003 Dec 12;278(50):49773-9. Epub 2003 Sep 30. [14522962 ]