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Identification
NameAspartame
Accession NumberDB00168  (NUTR00046)
TypeSmall Molecule
GroupsApproved, 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 Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AminosweetAjinomoto
CanderelMerisant
EqualMerisant
NutrasweetNutraSweet
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIZ0H242BBR1
CAS number22839-47-0
WeightAverage: 294.3031
Monoisotopic: 294.121571696
Chemical FormulaC14H18N2O5
InChI KeyInChIKey=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)[C@@H](N)CC(O)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid ester
  • Alpha-amino acid amide
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Fatty acid ester
  • Amino fatty acid
  • Fatty acyl
  • Benzenoid
  • N-acyl-amine
  • Fatty amide
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Methyl ester
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Carboxamide group
  • Carboxylic acid
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed as a diet supplement and sugar substitute.
PharmacodynamicsAspartame (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 action180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.
Related Articles
AbsorptionAbsorbed in the small intestine, aspartame is metabolized and absorbed very quickly.
Volume of distributionNot Available
Protein bindingNot 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 eliminationNot Available
Half lifeAt 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.
ClearanceNot Available
ToxicityMild gastrointestinal side effects including diarrhea have been reported.
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-0.8218
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Aspartame powder1.68USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting pointabout 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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00ns-0690000000-e92f66ca1ae82b0ccd81View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00di-2900000000-8eec324eec1e64466b1cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-01b9-2900000000-e8415697953bc139924bView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
Synthesis Reference

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

US5582351
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (71.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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
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
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 acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which in...
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
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 ]

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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
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, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23