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Record Information
Creation Date2006-03-08 13:09:08 UTC
Update Date2016-02-11 01:05:04 UTC
Secondary Accession NumbersNone
Metabolite Identification
Common NameAspartame
DescriptionAspartame is the name for an artificial, non-carbohydrate sweetener, aspartyl-phenylalanine-1-methyl ester; i.e., the methyl ester of the dipeptide of the amino acids aspartic acid and phenylalanine. It is marketed under a number of trademark names, such as Equal, and Canderel, and is an ingredient of approximately 6,000 consumer foods and beverages sold worldwide. It is commonly used in diet soft drinks, and is often provided as a table condiment. It is also used in some brands of chewable vitamin supplements. In the European Union, it is also known under the E number (additive code) E951. Aspartame is also one of the sugar substitutes used by diabetics. Upon ingestion, aspartame breaks down into several constituent chemicals, including the naturally-occurring essential amino acid phenylalanine which is a health hazard to the few people born with phenylketonuria, a congenital inability to process phenylalanine. Aspartic acid is an amino acid commonly found in foods. Approximately 40% of aspartame (by mass) is broken down into aspartic acid. Because aspartame is metabolized and absorbed very quickly (unlike aspartic acid-containing proteins in foods), it is known that aspartame could spike blood plasma levels of aspartate. Aspartic acid is in a class of chemicals known as excitotoxins. Abnormally high levels of excitotoxins have been shown in hundreds of animals studies to cause damage to areas of the brain unprotected by the blood-brain barrier and a variety of chronic diseases arising out of this neurotoxicity.
1-Methyl N-L-alpha-aspartyl-L-phenylalanateChEBI
3-amino-N-(alpha-Carboxyphenethyl)succinamic acid N-methyl esterChEBI
3-amino-N-(alpha-Methoxycarbonylphenethyl) succinamic acidChEBI
Aspartylphenylalanine methyl esterChEBI
L-Aspartyl-L-phenylalanine methyl esterChEBI
1-Methyl N-L-a-aspartyl-L-phenylalanateGenerator
1-Methyl N-L-a-aspartyl-L-phenylalanic acidGenerator
1-Methyl N-L-alpha-aspartyl-L-phenylalanic acidGenerator
1-Methyl N-L-α-aspartyl-L-phenylalanateGenerator
1-Methyl N-L-α-aspartyl-L-phenylalanic acidGenerator
3-amino-N-(a-Carboxyphenethyl)succinamate N-methyl esterGenerator
3-amino-N-(a-Carboxyphenethyl)succinamic acid N-methyl esterGenerator
3-amino-N-(alpha-Carboxyphenethyl)succinamate N-methyl esterGenerator
3-amino-N-(α-carboxyphenethyl)succinamate N-methyl esterGenerator
3-amino-N-(α-carboxyphenethyl)succinamic acid N-methyl esterGenerator
3-amino-N-(a-Methoxycarbonylphenethyl) succinamateGenerator
3-amino-N-(a-Methoxycarbonylphenethyl) succinamic acidGenerator
3-amino-N-(alpha-Methoxycarbonylphenethyl) succinamateGenerator
3-amino-N-(α-methoxycarbonylphenethyl) succinamateGenerator
3-amino-N-(α-methoxycarbonylphenethyl) succinamic acidGenerator
Dipeptide sweetenerHMDB
e 951HMDB
L-Aspartyl-L-3-phenylalanine methyl esterHMDB
L-Aspartyl-L-phenylalanyl methyl esterHMDB
Methyl aspartylphenylalanateHMDB
Pal sweetHMDB
Palsweet dietHMDB
Sweet dipeptideHMDB
Chemical FormulaC14H18N2O5
Average Molecular Weight294.3031
Monoisotopic Molecular Weight294.121571696
IUPAC Name(3S)-3-amino-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]carbamoyl}propanoic acid
Traditional Nameaspartame
CAS Registry Number22839-47-0
InChI Identifier
Chemical 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
  • 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
StatusDetected but not Quantified
  • Food
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
Experimental Properties
Melting Point246.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility0.65 mg/mLALOGPS
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
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
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
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Saliva
Tissue Location
  • Brain
PathwaysNot Available
Normal Concentrations
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00168
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB000569
KNApSAcK IDNot Available
Chemspider ID118630
KEGG Compound IDC11045
BioCyc IDCPD-5583
BiGG IDNot Available
Wikipedia LinkAspartame
NuGOwiki LinkHMDB01894
Metagene LinkHMDB01894
PubChem Compound134601
ChEBI ID2877
Synthesis ReferenceFuganti, Claudio; Grasselli, Piero; Malpezzi, Luciana; Casati, Paolo. Synthesis of aspartame via asymmetric hydrogenation of N-protected (Z)-N-a-L-aspartyl-D-phenylalanine methyl ester. Journal of Organic Chemistry (1986), 51(7), 1126-8.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Lam S: Stereoselective analysis of D and L dansyl amino acids as the mixed chelate copper(II) complexes by HPLC. J Chromatogr Sci. 1984 Sep;22(9):416-23. [6490790 ]
  2. Lam S, Azumaya H, Karmen A: High-performance liquid chromatography of amino acids in urine and cerebrospinal fluid. J Chromatogr. 1984 Oct 19;302:21-9. [6501504 ]
  3. Fernstrom JD: Dietary amino acids and brain function. J Am Diet Assoc. 1994 Jan;94(1):71-7. [7903674 ]
  4. Azcurra AI, Calamari SE, Yankilevich ER, Battellino LJ, Cattoni ST, Colantonio G: [Effects of local treatment with sodium fluoride mouthrinse on peroxidase and hypothiocyanite saliva levels in adolescent]/. Acta Physiol Pharmacol Ther Latinoam. 1997;47(4):211-20. [9504181 ]
  5. Busch U, Schmid J, Heinzel G, Schmaus H, Baierl J, Huber C, Roth W: Pharmacokinetics of meloxicam in animals and the relevance to humans. Drug Metab Dispos. 1998 Jun;26(6):576-84. [9616195 ]
  6. Bidiwala KS, Lorenz JM, Kleinman LI: Renal function correlates of postnatal diuresis in preterm infants. Pediatrics. 1988 Jul;82(1):50-8. [3288958 ]
  7. Burns TS, Stargel WW, Tschanz C, Kotsonis FN, Hurwitz A: Aspartame and sucrose produce a similar increase in the plasma phenylalanine to large neutral amino acid ratio in healthy subjects. Pharmacology. 1991;43(4):210-9. [1771173 ]
  8. Romano M, Casacci F, De Marchi F, Pacei T, Esteve A, Lomuscio G, Mennini T, Salmona M: Effects of aspartame and carbohydrate administration on human and rat plasma large neutral amino acid levels and rat brain amino acid and monoamine levels. J Nutr. 1989 Jan;119(1):75-81. [2913236 ]
  9. McMasters DR, Vedani A: Ochratoxin binding to phenylalanyl-tRNA synthetase: computational approach to the mechanism of ochratoxicosis and its antagonism. J Med Chem. 1999 Aug 12;42(16):3075-86. [10447951 ]
  10. Kochansky CJ, Rippley RK, Yan KX, Song H, Wallace MA, Dean D, Jones AN, Lasseter K, Schwartz J, Vincent SH, Franklin RB, Wagner J: Absorption, metabolism, and excretion of [14C]MK-0767 (2-methoxy-5-(2,4-dioxo-5-thiazolidinyl)-N-[[4-(trifluoromethyl)phenyl] methyl]benzamide) in humans. Drug Metab Dispos. 2006 Sep;34(9):1457-61. Epub 2006 Jun 13. [16772365 ]
  11. Koeppe RA, Shulkin BL, Rosenspire KC, Shaw LA, Betz AL, Mangner T, Price JC, Agranoff BW: Effect of aspartame-derived phenylalanine on neutral amino acid uptake in human brain: a positron emission tomography study. J Neurochem. 1991 May;56(5):1526-35. [2013754 ]
  12. Yang D, Beylot M, Agarwal KC, Soloviev MV, Brunengraber H: Assay of the human liver citric acid cycle probe phenylacetylglutamine and of phenylacetate in plasma by gas chromatography-mass spectrometry. Anal Biochem. 1993 Jul;212(1):277-82. [8368503 ]
  13. Maher TJ, Wurtman RJ: Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 1987 Nov;75:53-7. [3319565 ]
  14. Wurtman RJ, Maher TJ: Effects of oral aspartame on plasma phenylalanine in humans and experimental rodents. Short note. J Neural Transm. 1987;70(1-2):169-73. [3668518 ]


General function:
Involved in ion channel activity
Specific function:
Receptor-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. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL
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  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. [17567713 ]
General function:
Involved in G-protein coupled 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 essential for the recognition and response to the disaccharide trehalose. Sequence differences within and between species can significantly influence the selectivity and specificity of taste responses
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General function:
Involved in G-protein coupled receptor activity
Specific function:
Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners
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  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [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. [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. [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. [17168764 ]


General function:
Involved in transporter activity
Specific function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds
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  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. [12063169 ]
General function:
Involved in ion 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). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
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  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. [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. [10336520 ]