ContaminantDB: L-Histidine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (5)XML

Record Information

Version

1.0

Creation Date

2014-08-29 06:34:56 UTC

Update Date

2026-05-14 16:30:00 UTC

Accession Number

CHEM003323

Identification

Common Name

L-Histidine

Class

Small Molecule

Description

Histidine 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.

Contaminant Sources

Cosmetic Chemicals
EAFUS Chemicals
FooDB Chemicals
HMDB Contaminants - Feces
HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins

Contaminant 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

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(S)-4-(2-Amino-2-carboxyethyl)imidazole	ChEBI
(S)-alpha-Amino-1H-imidazole-4-propanoic acid	ChEBI
(S)-alpha-Amino-1H-imidazole-4-propionic acid	ChEBI
H	ChEBI
His	ChEBI
HISTIDINE	ChEBI
L-(-)-Histidine	ChEBI
L-Histidin	ChEBI
(S)-a-Amino-1H-imidazole-4-propanoate	Generator
(S)-a-Amino-1H-imidazole-4-propanoic acid	Generator
(S)-alpha-Amino-1H-imidazole-4-propanoate	Generator
(S)-Α-amino-1H-imidazole-4-propanoate	Generator
(S)-Α-amino-1H-imidazole-4-propanoic acid	Generator
(S)-a-Amino-1H-imidazole-4-propionate	Generator
(S)-a-Amino-1H-imidazole-4-propionic acid	Generator
(S)-alpha-Amino-1H-imidazole-4-propionate	Generator
(S)-Α-amino-1H-imidazole-4-propionate	Generator
(S)-Α-amino-1H-imidazole-4-propionic acid	Generator
(S)-1H-Imidazole-4-alanine	HMDB
(S)-2-Amino-3-(4-imidazolyl)propionsaeure	HMDB
(S)-Histidine	HMDB
(S)1H-Imidazole-4-alanine	HMDB
3-(1H-Imidazol-4-yl)-L-alanine	HMDB
Amino-1H-imidazole-4-propanoate	HMDB
Amino-1H-imidazole-4-propanoic acid	HMDB
Amino-4-imidazoleproprionate	HMDB
Amino-4-imidazoleproprionic acid	HMDB
Glyoxaline-5-alanine	HMDB
Histidine, L isomer	HMDB
Histidine, L-isomer	HMDB
L-Isomer histidine	HMDB
L-Histidine	KEGG

Chemical Formula

C₆H₉N₃O₂

Average Molecular Mass

155.155 g/mol

Monoisotopic Mass

155.069 g/mol

CAS Registry Number

71-00-1

IUPAC Name

(2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid

Traditional Name

L-histidine

SMILES

N[C@@H](CC1=CN=CN1)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 Key

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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Histidine 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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

proteinogenic amino acid (CHEBI:15971 )
L-alpha-amino acid (CHEBI:15971 )
histidine (CHEBI:15971 )
Common amino acids (C00135 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

All Tissues
Prostate

Pathways

Name	SMPDB Link	KEGG Link
Ammonia Recycling	SMP00009	map00910
Histidine Metabolism	SMP00044	map00340
Transcription/Translation	SMP00019	Not Available
Hartnup Disorder	SMP00189	Not Available
Histidinemia	SMP00191	Not Available

Applications

nutraceutical

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	287 dec°C
Boiling Point	Not Available
Solubility	4.56E+004 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	71.3 g/L	ALOGPS
logP	-2.7	ALOGPS
logP	-3.6	ChemAxon
logS	-0.34	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 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	38.06 m³·mol⁻¹	ChemAxon
Polarizability	14.67 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-0udi-0940000000-43b9b035189af65e19cb	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-0udi-0910000000-fc3ecec9d4ff3aa8cb09	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0udi-0910000000-8284a673a35f7ac2241f	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)	splash10-0fk9-8910000000-a3231b1a418b5798ecac	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-0udi-1920000000-227e8116769731104e82	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (4 TMS)	splash10-0ufu-2942100000-31605fd50ecc1f5be0ed	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0940000000-43b9b035189af65e19cb	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0910000000-fc3ecec9d4ff3aa8cb09	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0910000000-8284a673a35f7ac2241f	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-QQ (Non-derivatized)	splash10-0002-2901100000-ae0f3865934743de764c	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0fk9-8910000000-a3231b1a418b5798ecac	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0udi-1920000000-227e8116769731104e82	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0ufu-2942100000-31605fd50ecc1f5be0ed	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0ue9-0900000000-75e38a3f347210c301b0	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udi-0910000000-c54bd92cc112eec7e509	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-9500000000-1d29684ccb6383687865	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-03di-6900000000-1dd400a16b8067f4daea	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0a4i-0900000000-21530fac9975dc1edc7c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-053r-9300000000-a946c375931adb366aae	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-053r-9000000000-61a3602d80bc0d54c579	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-0900000000-7d63b501889c2628f4f0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-001i-0900000000-d4ccd4e44ca818b4cb17	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-0900000000-811aee5724fe0999c134	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-2900000000-052753eb699ae7cb4cb9	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-0900000000-3e145a05e6a71a0a2f56	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-0a4i-0900000000-143a4b9d88183bc5abe7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-03di-0900000000-a8c213472da676a241f2	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-001i-0900000000-dfdf9562f155abb5fdeb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0uk9-0879331100-8434b5b9e7e5700c2353	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-000i-0900000000-aaaaadcecd4cd7c94e1e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0udi-0900000000-90c4cbd09d7abc003013	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0udi-0900000000-1381708d18c24486773d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0w29-0696321100-eb62fc608270d1151707	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-000i-0900000000-3450566ff38e6506a70f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-01q9-7900000000-124509a66476629ce10a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negative	splash10-0udi-0900000000-efa6a21b1be16fda0802	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-0udi-0900000000-137840e69da48c6114e4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-0udu-3900000000-06d50e90c797793a72d7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-0006-9100000000-de7c9eb8068ef4f39f85	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-00l6-9000000000-ebf778679d4c6d6a6057	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-014i-9000000000-08d0188684283d1b2372	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-0a4i-0900000000-46c2f608d27f0381a039	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-9100000000-ae0a0b81669663b3b4a5	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

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.
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.

Metabolism

Not Available

Toxicity Values

ORL-RAT LD₅₀ > 15000 mg/kg, IPR-RAT LD₅₀ > 8000 mg/kg, ORL-MUS LD₅₀ > 15000 mg/kg, IVN-MUS LD₅₀ > 2000 mg/kg

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID