Identification

Name
Aspartame
Accession Number
DB00168  (NUTR00046)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Flavoring agent sweeter than sugar, metabolized as phenylalanine and aspartic acid. [PubChem]

Structure
Thumb
Synonyms
  • 1-Methyl N-L-alpha-aspartyl-L-phenylalanate
  • 1-Methyl N-L-alpha-aspartyl-L-phenylalanine
  • 1-methyl N-L-α-aspartyl-L-phenylalanate
  • 3-Amino-N-(alpha-carboxyphenethyl)succinamic acid N-methyl ester
  • 3-Amino-N-(alpha-methoxycarbonylphenethyl) succinamic acid
  • 3-Amino-N-(α-carboxyphenethyl)succinamic acid N-methyl ester
  • 3-Amino-N-(α-methoxycarbonylphenethyl) succinamic acid
  • Asp-phe-ome
  • Aspartam
  • Aspartame
  • Aspartamo
  • Aspartamum
  • Aspartylphenylalanine methyl ester
  • L-Aspartyl-L-phenylalanine methyl ester
External IDs
E-951 / SC-18862
International/Other Brands
Aminosweet (Ajinomoto) / Canderel (Merisant) / Equal (Merisant) / Nutrasweet (NutraSweet)
Categories
UNII
Z0H242BBR1
CAS number
22839-47-0
Weight
Average: 294.3031
Monoisotopic: 294.121571696
Chemical Formula
C14H18N2O5
InChI Key
IAOZJIPTCAWIRG-QWRGUYRKSA-N
InChI
InChI=1S/C14H18N2O5/c1-21-14(20)11(7-9-5-3-2-4-6-9)16-13(19)10(15)8-12(17)18/h2-6,10-11H,7-8,15H2,1H3,(H,16,19)(H,17,18)/t10-,11-/m0/s1
IUPAC Name
(3S)-3-amino-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]carbamoyl}propanoic acid
SMILES
COC(=O)[[email protected]](CC1=CC=CC=C1)NC(=O)[[email protected]@H](N)CC(O)=O

Pharmacology

Indication

Used as a diet supplement and sugar substitute.

Structured Indications
Not Available
Pharmacodynamics

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.

Mechanism of action

180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.

TargetActionsOrganism
UTransient receptor potential cation channel subfamily V member 1
inducer
Human
UTaste receptor type 1 member 2
agonist
Human
UTaste receptor type 1 member 3Not AvailableHuman
Absorption

Absorbed in the small intestine, aspartame is metabolized and absorbed very quickly.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Approximately 10% of aspartame (by weight) is broken down into methanol in the small intestine. Most of the methanol is absorbed and quickly converted into formaldehyde. Approximately 50% of aspartame (by weight) is broken down into phenylalanine. Approximately 40% of aspartame (by mass) is broken down into aspartic acid.

Route of elimination
Not Available
Half life

At room temperature, aspartame is most stable at pH 4.3, where its half-life is nearly 300 days. At pH 7 however, its half-life is only a few days.

Clearance
Not Available
Toxicity

Mild gastrointestinal side effects including diarrhea have been reported.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Josef Tsau, "Convenient to use aspartame and method of making." U.S. Patent US5582351, issued August, 1972.

US5582351
General References
Not Available
External Links
Human Metabolome Database
HMDB01894
KEGG Drug
D02381
KEGG Compound
C11045
PubChem Compound
134601
PubChem Substance
46507278
ChemSpider
118630
ChEBI
2877
ChEMBL
CHEMBL171679
PharmGKB
PA448493
HET
PME
Wikipedia
Aspartame
PDB Entries
1a8j / 3mgc
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Aspartame powder1.68USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)about 190 and 245-247Schlatter, J.M.; US.Patent 3,492,131; January 27, 1970; assigned to G.D. Searle & Co.
water solubilityThe solubility of aspartame in water is dependent on pH and temperature, the maximum solubility is reached at pH 2.2 (20 mg/mL at 25 °C) and the minimum solubility at pH 5.2 (pHi) is 13.5 mg/mL at 25 °C.Not Available
logP-0.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.652 mg/mLALOGPS
logP-1.2ALOGPS
logP-2.2ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.53ChemAxon
pKa (Strongest Basic)8.53ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.72 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity73.22 m3·mol-1ChemAxon
Polarizability29.58 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8218
Blood Brain Barrier-0.5562
Caco-2 permeable-0.8956
P-glycoprotein substrateSubstrate0.5137
P-glycoprotein inhibitor INon-inhibitor0.9286
P-glycoprotein inhibitor IINon-inhibitor0.9772
Renal organic cation transporterNon-inhibitor0.9573
CYP450 2C9 substrateNon-substrate0.833
CYP450 2D6 substrateNon-substrate0.8474
CYP450 3A4 substrateNon-substrate0.6928
CYP450 1A2 substrateNon-inhibitor0.8972
CYP450 2C9 inhibitorNon-inhibitor0.894
CYP450 2D6 inhibitorNon-inhibitor0.9549
CYP450 2C19 inhibitorNon-inhibitor0.9484
CYP450 3A4 inhibitorNon-inhibitor0.9437
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9792
Ames testNon AMES toxic0.7963
CarcinogenicityNon-carcinogens0.9284
BiodegradationNot ready biodegradable0.7073
Rat acute toxicity1.6896 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9948
hERG inhibition (predictor II)Non-inhibitor0.9467
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-00ns-0690000000-e92f66ca1ae82b0ccd81
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-00di-2900000000-8eec324eec1e64466b1c
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-01b9-2900000000-e8415697953bc139924b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00e9-0930000000-d8dbb5a34c019dc70708
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0080-0890000000-b2e2c2a89ceaf3d1f9db
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Peptides
Alternative Parents
Phenylalanine and derivatives / Alpha amino acid esters / N-acyl-alpha amino acids and derivatives / Beta amino acids and derivatives / Amphetamines and derivatives / Fatty acid esters / Dicarboxylic acids and derivatives / Methyl esters / Amino acids / Propargyl-type 1,3-dipolar organic compounds
show 7 more
Substituents
Alpha peptide / Phenylalanine or derivatives / Alpha-amino acid ester / N-acyl-alpha amino acid or derivatives / Beta amino acid or derivatives / Alpha-amino acid or derivatives / Amphetamine or derivatives / Fatty acid ester / Monocyclic benzene moiety / Fatty acyl
show 23 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
dipeptide, methyl ester, carboxylic acid (CHEBI:2877)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Transmembrane signaling receptor activity
Specific Function
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular aci...
Gene Name
TRPV1
Uniprot ID
Q8NER1
Uniprot Name
Transient receptor potential cation channel subfamily V member 1
Molecular Weight
94955.33 Da
References
  1. Riera CE, Vogel H, Simon SA, le Coutre J: Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors. Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R626-34. Epub 2007 Jun 13. [PubMed:17567713]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Taste receptor activity
Specific Function
Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners.
Gene Name
TAS1R2
Uniprot ID
Q8TE23
Uniprot Name
Taste receptor type 1 member 2
Molecular Weight
95182.54 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. [PubMed: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. [PubMed:17016423]
  3. Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X: Different functional roles of T1R subunits in the heteromeric taste receptors. Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14258-63. Epub 2004 Sep 7. [PubMed:15353592]
  4. Cui M, Jiang P, Maillet E, Max M, Margolskee RF, Osman R: The heterodimeric sweet taste receptor has multiple potential ligand binding sites. Curr Pharm Des. 2006;12(35):4591-600. [PubMed:17168764]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Taste receptor activity
Specific Function
Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate). TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners. TAS1R3 is essenti...
Gene Name
TAS1R3
Uniprot ID
Q7RTX0
Uniprot Name
Taste receptor type 1 member 3
Molecular Weight
93385.155 Da
References
  1. Maillet EL, Cui M, Jiang P, Mezei M, Hecht E, Quijada J, Margolskee RF, Osman R, Max M: Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. Chem Senses. 2015 Oct;40(8):577-86. doi: 10.1093/chemse/bjv045. [PubMed:26377607]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456]
  2. Tsuda M, Sekine T, Takeda M, Cha SH, Kanai Y, Kimura M, Endou H: Transport of ochratoxin A by renal multispecific organic anion transporter 1. J Pharmacol Exp Ther. 1999 Jun;289(3):1301-5. [PubMed:10336520]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [PubMed:11669456]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. [PubMed:12063169]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:32