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Identification
NameL-Histidine
Accession NumberDB00117  (NUTR00030)
TypeSmall Molecule
GroupsApproved, Nutraceutical
Description

An essential amino acid that is required for the production of histamine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-4-(2-Amino-2-carboxyethyl)imidazoleNot AvailableNot Available
(S)-a-Amino-1H-imidazole-4-propanoic acidNot AvailableNot Available
(S)-alpha-amino-1H-Imidazole-4-propanoic acidNot AvailableNot Available
(S)-alpha-Amino-1H-imidazole-4-propionic acidNot AvailableNot Available
(S)-α-amino-1H-Imidazole-4-propanoic acidNot AvailableNot Available
HNot AvailableNot Available
HisNot AvailableNot Available
HistidineNot AvailableNot Available
L-(-)-HistidineNot AvailableNot Available
L-(−)-histidineNot AvailableNot Available
L-HistidinNot AvailableNot Available
L-HistidineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number71-00-1
WeightAverage: 155.1546
Monoisotopic: 155.069476547
Chemical FormulaC6H9N3O2
InChI KeyHNDVDQJCIGZPNO-YFKPBYRVSA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid
SMILES
N[C@@H](CC1=CN=CN1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as d-alpha-amino acids. These are alpha amino acids which have the D-configuration of the alpha-carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentD-alpha-amino acids
Alternative Parents
Substituents
  • D-alpha-amino acid
  • Imidazolyl carboxylic acid derivative
  • Aralkylamine
  • Amino fatty acid
  • Fatty acyl
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationThe 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.
PharmacodynamicsIs found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.
Mechanism of actionSince 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.
AbsorptionAbsorbed from the small intestine via an active transport mechanism requiring the presence of sodium.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityORL-RAT LD50 > 15000 mg/kg, IPR-RAT LD50 > 8000 mg/kg, ORL-MUS LD50 > 15000 mg/kg, IVN-MUS LD50 > 2000 mg/kg; Mild gastrointestinal side effects.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8921
Blood Brain Barrier+0.7546
Caco-2 permeable-0.6669
P-glycoprotein substrateNon-substrate0.6143
P-glycoprotein inhibitor INon-inhibitor0.9889
P-glycoprotein inhibitor IINon-inhibitor0.9923
Renal organic cation transporterNon-inhibitor0.907
CYP450 2C9 substrateNon-substrate0.8647
CYP450 2D6 substrateNon-substrate0.8235
CYP450 3A4 substrateNon-substrate0.8363
CYP450 1A2 substrateNon-inhibitor0.9815
CYP450 2C9 substrateNon-inhibitor0.9646
CYP450 2D6 substrateNon-inhibitor0.9566
CYP450 2C19 substrateNon-inhibitor0.9656
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9798
Ames testNon AMES toxic0.7016
CarcinogenicityNon-carcinogens0.9206
BiodegradationNot ready biodegradable0.569
Rat acute toxicity1.7719 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9893
hERG inhibition (predictor II)Non-inhibitor0.9551
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
L-histidine mhc crystals0.32USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point287 dec °CPhysProp
water solubility4.56E+004 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-3.32CHMELIK,J ET AL. (1991)
logS-0.53ADME Research, USCD
pKa2.76 (at 0 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility62.0 mg/mLALOGPS
logP-3.1ALOGPS
logP-3.6ChemAxon
logS-0.4ALOGPS
pKa (Strongest Acidic)1.85ChemAxon
pKa (Strongest Basic)9.44ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity38.06 m3·mol-1ChemAxon
Polarizability14.67 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.24 KB)
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
References
Synthesis Reference

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

US4495283
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (72.7 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Histidine decarboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Histidine decarboxylase P19113 Details

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
  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
  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
  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
  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

2. Histidine--tRNA ligase, cytoplasmic

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Histidine--tRNA ligase, cytoplasmic P12081 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
  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

3. Sodium-coupled neutral amino acid transporter 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-coupled neutral amino acid transporter 3 Q99624 Details

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
  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
  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

4. Histidine ammonia-lyase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Histidine ammonia-lyase P42357 Details

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
  2. Lambrecht NW, Yakubov I, Sachs G: Fasting induced changes in ECL cell gene expression. Physiol Genomics. 2007 May 29;. Pubmed
  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
  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

Transporters

1. Monocarboxylate transporter 10

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 10 Q8TF71 Details

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
  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

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Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 10:17