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Record Information
Version4.0
StatusDetected but not Quantified
Creation Date2006-03-08 13:09:08 UTC
Update Date2017-12-07 01:46:18 UTC
HMDB IDHMDB0001894
Secondary Accession Numbers
  • HMDB01894
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.
Structure
Thumb
Synonyms
ValueSource
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
Asp-phe-omeChEBI
AspartamChEBI
AspartamoChEBI
AspartamumChEBI
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
CanderelHMDB
Dipeptide sweetenerHMDB
e 951HMDB
L-Aspartyl-L-3-phenylalanine methyl esterHMDB
L-Aspartyl-L-phenylalanyl methyl esterHMDB
Methyl aspartylphenylalanateHMDB
NutraSweetHMDB
Pal sweetHMDB
Palsweet dietHMDB
Sweet dipeptideHMDB
Methyl aspartylphenylalanineMeSH
Methyl ester, aspartylphenylalanineMeSH
muro Brand OF aspartameMeSH
Aspartame hermes brandMeSH
Aspartame prodes brandMeSH
Aspartylphenylalanine, methylMeSH
GoldswiteMeSH
Hermesetas goldMeSH
Aspartame fuca brandMeSH
Aspartame muro brandMeSH
Diététiques et santé brand OF aspartameMeSH
Fuca brand OF aspartameMeSH
Prodes brand OF aspartameMeSH
Tri sweetMeSH
Gold, hermesetasMeSH
Hermes brand OF aspartameMeSH
MilisucreMeSH
NozucarMeSH
Tri-sweetMeSH
TriSweetMeSH
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
SMILES
COC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CC(O)=O
InChI Identifier
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
InChI KeyIAOZJIPTCAWIRG-QWRGUYRKSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentPeptides
Alternative Parents
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
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Methyl ester
  • Amino acid or derivatives
  • Amino acid
  • Carboxylic acid ester
  • Organic 1,3-dipolar compound
  • Carboximidic acid
  • Carboximidic acid derivative
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Primary amine
  • Organooxygen compound
  • Primary aliphatic amine
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Biofluid and excreta:

  Organ and components:

Source:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point246.5 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.65 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity73.22 m³·mol⁻¹ChemAxon
Polarizability29.58 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-9220000000-2625126bd17025b83933View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-03di-5904000000-075be5fd36b94f425650View in MoNA
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
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0080-0890000000-b2e2c2a89ceaf3d1f9dbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00e9-0930000000-d8dbb5a34c019dc70708View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0080-0890000000-b2e2c2a89ceaf3d1f9dbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004j-4390000000-5ea0d55c8c75f40eefdeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0109-9730000000-badb4105789050b52346View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9100000000-22c71b3445a360c7886aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0290000000-c48af459412db76084ccView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02bg-1690000000-df82228a7343c200b8d4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03gu-9700000000-db183663829759af70f9View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Saliva
Tissue Location
  • Brain
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
SalivaDetected but not Quantified Adult (>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
METLIN ID6377
PubChem Compound134601
PDB IDPME
ChEBI ID2877
References
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. [PubMed: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. [PubMed:6501504 ]
  3. Fernstrom JD: Dietary amino acids and brain function. J Am Diet Assoc. 1994 Jan;94(1):71-7. [PubMed: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. [PubMed: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. [PubMed:9616195 ]
  6. Bidiwala KS, Lorenz JM, Kleinman LI: Renal function correlates of postnatal diuresis in preterm infants. Pediatrics. 1988 Jul;82(1):50-8. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:8368503 ]
  13. Maher TJ, Wurtman RJ: Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 1987 Nov;75:53-7. [PubMed: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. [PubMed:3668518 ]

Enzymes

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
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
Molecular weight:
94955.3
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 ]
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
Gene Name:
TAS1R3
Uniprot ID:
Q7RTX0
Molecular weight:
93385.2
General function:
Involved in G-protein coupled receptor activity
Specific function:
Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners
Gene Name:
TAS1R2
Uniprot ID:
Q8TE23
Molecular weight:
95182.5
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 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular weight:
59970.9
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 ]
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
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
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 ]