Banner
targets (4) transporters (1)
for drugs
Identification
Name L-Histidine
Accession Number DB00117 (NUTR00030)
Type small molecule
Groups approved, nutraceutical
Description

An essential amino acid that is required for the production of histamine. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(S)-4-(2-Amino-2-carboxyethyl)imidazole
(S)-a-Amino-1H-imidazole-4-propanoic acid
(S)-alpha-Amino-1H-imidazole-4-propionic acid
(S)-Histidine
Glyoxaline-5-alanine
Histidine
L-(-)-Histidine
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Conditionally Essential Amino Acids
CAS number 71-00-1
Weight Average: 155.1546
Monoisotopic: 155.069476547
Chemical Formula C6H9N3O2
InChI Key InChIKey=HNDVDQJCIGZPNO-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
Plain Text
IUPAC Name
(2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid
SMILES
N[C@@H](CC1=CN=CN1)C(O)=O
Plain Text
Mass Spec show (7.24 KB)
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Cyanamides
Pharmacology
Indication The 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.
Pharmacodynamics Is 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 action Since 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.
Absorption Absorbed from the small intestine via an active transport mechanism requiring the presence of sodium.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity ORL-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
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Powder Oral
Tablet Oral
Prices
Unit description Cost Unit
L-histidine mhc crystals 0.32 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 287 dec °C PhysProp
water solubility 4.56E+004 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP -3.32 CHMELIK,J ET AL. (1991)
logS -0.53 ADME Research, USCD
pKa 2.76 (at 0 °C) KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 6.20e+01 g/l ALOGPS
logP -3.1 ALOGPS
logP -3.6 ChemAxon
logS -0.4 ALOGPS
pKa (strongest acidic) 1.85 ChemAxon
pKa (strongest basic) 9.44 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 92 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 38.06 ChemAxon
polarizability 14.67 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00032 Link_out
KEGG Compound C00135 Link_out
PubChem Compound 6274 Link_out
PubChem Substance 46507001 Link_out
ChemSpider 6038 Link_out
BindingDB 7953 Link_out
ChEBI 15971 Link_out
ChEMBL 15971 Link_out
PharmGKB PA449882 Link_out
IUPHAR 3310 Link_out
Guide to Pharmacology 3310 Link_out
HET HIS Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lhi_0137.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/L-Histidine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (72.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Histidine decarboxylase

Pharmacological action: unknown
Organism class: human
UniProt ID: P19113 Link_out
Gene: HDC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Histidyl-tRNA synthetase, cytoplasmic

Pharmacological action: unknown
Organism class: human
UniProt ID: P12081 Link_out
Gene: HARS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. System N amino acid transporter 1

Pharmacological action: unknown

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

Organism class: human
UniProt ID: Q99624 Link_out
Gene: SLC38A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Organism class: human
UniProt ID: P42357 Link_out
Gene: HAL Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

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 (By similarity)

UniProt ID: Q8TF71 Link_out
Gene: SLC16A10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19