L-HISTIDINE
Relevant Data
Food Additives Approved in the United States
Flavouring Substances Approved by European Union:
General Information
| Chemical Names: | L-HISTIDINE |
| CAS number: | 71-00-1 |
| JECFA number: | 1431 |
| FEMA number: | 3694 |
| Functional Class: |
Flavouring Agent FLAVOURING_AGENT |
From apps.who.int
Evaluations
| Evaluation year: | 2004 |
| ADI: | No safety concern at current levels of intake when used as a flavouring agent |
| Comments: | Not evaluated using the Procedure for the Safety Evaluation of Flavouring Agents; the substance is a macronutrient and a normal component of protein and, as such, human exposure through food is orders of magnitude higher than the anticipated level of exposure from use as a flavouring agent |
| Report: | TRS 928-JECFA 63/98 |
| Tox Monograph: | FAS 54-JECFA 63/435 |
| Specification: | COMPENDIUM ADDENDUM 12/FNP 52 Add. 12/90 |
From apps.who.int
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 6274 |
| IUPAC Name | (2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid |
| 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 |
| InChI Key | HNDVDQJCIGZPNO-YFKPBYRVSA-N |
| Canonical SMILES | C1=C(NC=N1)CC(C(=O)O)N |
| Molecular Formula | C6H9N3O2 |
| Wikipedia | L-Histidine |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 155.157 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Complexity | 151.0 |
| CACTVS Substructure Key Fingerprint | A A A D c c B j M A A A A A A A A A A A A A A A A A A A A W A A A A A A A A A A A A A A A A A B g A A A H g A Q C A A A C C j B l g Q t m B b J k g C o A R T 3 b A A A g C 2 x E q A B U Y G 4 c A i C a B J A 2 Q G U Q A A M k A J A Q C C 8 E Q I A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 92.0 |
| Monoisotopic Mass | 155.069 |
| Exact Mass | 155.069 |
| XLogP3 | None |
| XLogP3-AA | -3.2 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 11 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7546 |
| Human Intestinal Absorption | HIA+ | 0.8921 |
| Caco-2 Permeability | Caco2- | 0.6669 |
| P-glycoprotein Substrate | Non-substrate | 0.6143 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9889 |
| Non-inhibitor | 0.9923 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9070 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.4705 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8647 |
| CYP450 2D6 Substrate | Non-substrate | 0.8235 |
| CYP450 3A4 Substrate | Non-substrate | 0.8363 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9815 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9646 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9566 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9656 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9798 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9893 |
| Non-inhibitor | 0.9551 | |
| AMES Toxicity | Non AMES toxic | 0.7016 |
| Carcinogens | Non-carcinogens | 0.9206 |
| Fish Toxicity | Low FHMT | 0.8166 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.5261 |
| Honey Bee Toxicity | Low HBT | 0.7855 |
| Biodegradation | Not ready biodegradable | 0.5690 |
| Acute Oral Toxicity | III | 0.5849 |
| Carcinogenicity (Three-class) | Non-required | 0.6929 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -0.7796 | LogS |
| Caco-2 Permeability | -0.0852 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.7719 | LD50, mol/kg |
| Fish Toxicity | 2.8023 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.3083 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Absorbed from the small intestine via an active transport mechanism requiring the presence of sodium. |
|---|---|
| Mechanism of Toxicity | 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. <br/>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. <br/>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. |
| Metabolism | None |
| Toxicity Values | ORL-RAT LD<sub>50</sub> > 15000 mg/kg, IPR-RAT LD<sub>50</sub> > 8000 mg/kg, ORL-MUS LD<sub>50</sub> > 15000 mg/kg, IVN-MUS LD<sub>50</sub> > 2000 mg/kg |
| Lethal Dose | None |
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
| Minimum Risk Level | None |
| Health Effects | None |
| Treatment | None |
| Reference |
|
From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Amino acids, peptides, and analogues |
| Intermediate Tree Nodes | Amino acids and derivatives - Alpha amino acids and derivatives |
| Direct Parent | Histidine and derivatives |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as histidine and derivatives. These 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. |
From ClassyFire
Targets
- 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
- 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 ]
- 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
- 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 ]
- General Function:
- Histidine-trna ligase activity
- Gene Name:
- HARS
- Uniprot ID:
- P12081
- Molecular Weight:
- 57409.97 Da
References
- 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 ]
- 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
References
- 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 ]
From T3DB