aspartic acid.pdf

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NIH U.S. National Library of Medicine National Center for Biotechnology Information

D A T A B A S E

L-aspartic acid

Vendors

Drug Information

Pharmacology

Literature

Patents

Bioactivities

from MeSH [34]

PubChem CID: 5960

Chemical Names: L-aspartic acid; aspartic acid; Asparagic acid; L-aspartate; Asparaginic acid;

(2S)-Aspartic acid; More...

Molecular Formula: C H NO

Molecular Weight: 133.10268 g/mol

InChI Key: CKLJMWTZIZZHCS-REOHCLBHSA-N

UNII: 30KYC7MIAI

Create Date: 2004-09-16

One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in

sugar cane and sugar beets. It may be a neurotransmitter.

Cite this Record

4 7 4

partic acid | C4H7NO4 - PubChem http://pubchem.ncbi.nlm.nih.gov/compoun

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Contents

1 2D Structure

2 3D Conformer

3 Identification

4 Chemical and Physical Properties

5 Related Records

6 Chemical Vendors

7 Drug and Medication Information

8 Pharmacology and Biochemistry

9 Use and Manufacturing

10 Safety and Hazards

11 Toxicity

12 Literature

13 Patents

14 Biomolecular Interactions and Pathways

15 Biological Test Results

16 Classification

17 Information Sources


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from PubChem [33]

1 2D Structure

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from PubChem [33]

2 3D Conformer

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Show Hydrogens Show Atoms Animate

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3 Identification

3.1 Computed Descriptors

from PubChem [33](2S)-2-aminobutanedioic acid

3.1.1 IUPAC Name

from PubChem [33]InChI=1S/C4H7NO4/c5-2(4(8)9)1-3(6)7/h2H,1,5H2,(H,6,7)(H,8,9)/t2-/m0/s1

3.1.2 InChI

from PubChem [33]CKLJMWTZIZZHCS-REOHCLBHSA-N

3.1.3 InChI Key

from PubChem [33]C(C(C(=O)O)N)C(=O)O

3.1.4 Canonical SMILES

from PubChem [33]C([C@@H](C(=O)O)N)C(=O)O

3.1.5 Isomeric SMILES

3.2 Other Identifiers

from DrugBank [2] http://www.drugbank.ca/drugs/DB00128

from EPA Chemical Data Report [27] http://www.epa.gov/cdr/

56-84-8

56-84-8

3.2.1 CAS

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439

from ECHA [29] http://echa.europa.eu/

200-291-6

200-291-6

3.2.2 EC Number


3.2.3 ICSC Number

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439CI9098500

3.2.4 RTECS Number


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from FDA/SPL Indexing data [32] http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling

/ucm377913.htm

30KYC7MIAI

3.2.5 UNII

from Wiki [30] http://en.wikipedia.org/wiki/Aspartic_acid

from Wiki [31] http://en.wikipedia.org/wiki/Polyaspartic_acid

Aspartic acid

Polyaspartic acid

3.2.6 Wikipedia

3.3 Synonyms

from MeSH [34] http://www.ncbi.nlm.nih.gov/mesh/68001224

(+-)-Aspartic Acid1.

(R,S)-Aspartic Acid2.

Ammonium Aspartate3.

Aspartate4.

Aspartate Magnesium Hydrochloride5.

Aspartate, Ammonium6.

Aspartate, Calcium7.

Aspartate, Dipotassium8.

Aspartate, Disodium9.

Aspartate, Magnesium10.

Aspartate, Monopotassium11.

Aspartate, Monosodium12.

Aspartate, Potassium13.

Aspartate, Sodium14.

Aspartic Acid15.

Aspartic Acid, Ammonium Salt16.

Aspartic Acid, Calcium Salt17.

Aspartic Acid, Dipotassium Salt18.

Aspartic Acid, Disodium Salt19.

Aspartic Acid, Hydrobromide20.

Aspartic Acid, Hydrochloride21.

Aspartic Acid, Magnesium (1:1) Sa22.

Aspartic Acid, Magnesium (2:1) Sa23.

Aspartic Acid, Magnesium-Potassi24.

Aspartic Acid, Monopotassium Salt25.

Aspartic Acid, Monosodium Salt26.

Aspartic Acid, Potassium Salt27.

Aspartic Acid, Sodium Salt28.

Calcium Aspartate29.

Dipotassium Aspartate30.

3.3.1 MeSH Synonyms

from PubChem [33]

L-aspartic acid1.

aspartic acid2.

Asparagic acid3.

L-aspartate4.

Asparaginic acid5.

(2S)-Aspartic acid6.

H-Asp-OH7.

aspartate8.

L-Asparaginic acid9.

56-84-810.

(S)-Aspartic acid11.

L-Aminosuccinic acid12.

L-Asparagic acid13.

Aspatofort14.

(S)-2-Aminosuccinic acid15.

L-Aspartinsaeure16.

(S)-Aminobutanedioic acid17.

L-Asparaginsaeure18.

(2S)-2-aminobutanedioic acid19.

L-Asparaginsyra20.

Acidum asparticum21.

Aspartic acid, L-22.

(+)-Aspartic acid23.

Asparaginsaeure [German]24.

Aspartate, L-25.

L-2-Aminobutanedioic acid26.

(L)-ASPARTIC ACID27.

Aminosuccinic acid28.

L-Asp29.

Aspartic acid (VAN)30.

Asparagic acid (VAN31.

Acide aspartique [IN32.

Acido aspartico [INN33.

L-(+)-Aspartic acid34.

Acido aspartico35.

Asparaginic acid (VA36.

Acide aspartique37.

Butanedioic acid, am38.

L( )-Aminobernsteins39.

(L)-Aspartate40.

3.3.2 Depositor-Supplied Synonyms


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4 Chemical and Physical Properties

from PubChem [33]

Molecular Weight 133.10268 g/mol

Molecular Formula C H NO

XLogP3 -2.8

Hydrogen Bond Donor Count 3

Hydrogen Bond Acceptor Count 5

Rotatable Bond Count 3

Exact Mass 133.037508 g/mol

Monoisotopic Mass 133.037508 g/mol

Topological Polar Surface Area 101 A^2

Heavy Atom Count 9

Formal Charge 0

Complexity 133

Isotope Atom Count 0

Defined Atom Stereocenter Count 1

Undefined Atom Stereocenter Count 0

Defined Bond Stereocenter Count 0

Undefined Bond Stereocenter Count 0

Covalently-Bonded Unit Count 1

CACTVS Substructure Key Fingerprint AAADcYBiOAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Compound Is Canonicalized true

4.1 Computed Properties

4 7 4

4.2 Experimental Properties

from EPA Chemical Data Report [27] http://www.epa.gov/cdr/


PelletsLargeCrystals; DryPowder

COLOURLESS CRYSTALS.

4.2.1 Physical Description

White, crystalline solid

4.2.2 Color


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from HSDB [1] http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+56-84-8


Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 97

Orthorhombic bisphenoidal leaflets or rods

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station,

NJ: Merck and Co., Inc., 2001., p. 143



Acidic/neutral

Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers,

1985 to Present., p. VA2: 79 (1985)

Sour

Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p.

V2: 559 (1992)

4.2.3 Taste




270-271 deg C



270 C

PhysProp

270 C

4.2.4 Melting Point




1 g in 222.2 ml water at 20 deg C; 1 g in 149.9 ml water at 30 deg C; more sol in salt soln; sol in acids, alkalies



Insoluble in ethanol, ethyl ether, benzene; soluble in dilute HCl, pyridine

Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL

2005, p. 3-30

In water, 5,360 mg/L at 25 deg C

Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for

Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 105

Water Solubility (5390 mg/L (at 25 C))

YALKOWSKY,SH & DANNENFELSER,RM (1992)

4.2.5 Solubility


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from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Solubility in water, g/100ml: 0.45



1.6603 at 13 deg C

Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL

2005, p. 3-30

1.7 g/cm3

4.2.6 Density


2.6X10-7 mm Hg at 25 deg C (est)

US EPA; Estimation Program Interface (EPI) Suite. Ver.3.12. Nov 30, 2004. Available from, as of Oct 26, 2006:

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

4.2.7 Vapor Pressure




log Kow = -3.89

Chmelik J et al; Coll Czech Chem Commun 56: 2030-2041 (1991)

-3.89

CHMELIK,J ET AL. (1991)

-3.89

4.2.8 LogP

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Decomposes at 324C

4.2.9 Decomposition


2.01 (at 0 C)

KORTUM,G ET AL (1961)

4.2.10 pKa


pK1 = 1.92 (COOH); pK2 =3.87 (COOH); pK3 = 9.87 (amine)

Sergeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution, IUPAC Chemical Data Series No. 2, New

York, NY: Pergamon Press, p. 95 (1979)

4.2.11 Dissociation Constants


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ASPARTIC ACID HAS RELATIVELY HIGH SOUR, RELATIVELY LOW MSG-LIKE TASTE INTENSITIES /ASPARTIC

ACID/

Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed.

Cleveland: The Chemical Rubber Co., 1975., p. 824

DECOMPOSES AT 324 DEG C (RAPID HEATING)

Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-130

Isoelectric point = 2.98


1985 to Present., p. V2: 62 (1985)

Forms supersaturated soln easily



13C NMR: 479 (Stothers. Carbon-13 NMR Spectroscopy, Academic Press, New York) /DL-Aspartic Acid)

Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL.

1994., p. V1: 230

UV: 1-30 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /dl-Aspartic acid/


1994., p. V1: 230

MASS: 76392 (NIST/EPA/MSDC Mass Spectral Database, 1990 version); 290 (National Bureau of Standards EPA-NIH

Mass Spectra Data Base, NSRDS-NBS-63) /DL-Aspartic acid/


1994., p. V1: 320

Specific optical rotation: -2.0 deg at 25 deg C (c=3.93 in 5N HCl) /d-Aspartic acid/



Henry's Law constant = 1.1X10-14 atm-cu m/mol at 25 deg C (est)



Hydroxyl radical reaction rate constant = 4.0X10-11 cm3/molc-sec at 25 deg C (est)



4.2.12 Other Experimental Properties


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Specific optical rotation: +25.0 deg (c= 1.97 g in 100 ml 6 N hydrochloric acid) at 20 deg C/D



SPECIFIC OPTICAL ROTATION (WATER): +4.36 DEG @ 20 DEG C/DWeast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-130

IR: 18085 (Sadtler Research Laboratories IR Grating Collection)


1994., p. v1: 320

MASS: 30615 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)


1994., p. V1: 320

UV: 1-30 (Phillip et al., Organic Electronic Spectral Data, John Wiley & Sons, NY)


1994., p. V1: 320

4.3 Spectral Properties


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5 Related Records

from PubChem [33]

5.1 Related Compounds with Annotation

from PubChem [33]

Same Tautomer 52

Same Connectivity 50

Same Stereo 30

Same Isotope 3

Same Parent, Tautomer 435

Same Parent, Connectivity 433

Same Parent, Stereo 190

Same Parent, Isotope 385

Same Parent, Exact 161

Mixtures, Components, and Neutralized Forms 683

Similar Compounds 367

Similar Conformers 2788

5.2 Related Compounds

from PubChem [33]

All 1400

Same 184

Mixture 1216

5.3 Related Substances

CLICK TO LOAD...


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from PubChem [33]

PubMed 15439

Protein Structures 72

5.4 Entrez Crosslinks


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from PubChem [33]

6 Chemical Vendors

CLICK TO LOAD...


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7 Drug and Medication Information






MEDICATION (VET): TO REDUCE AMMONIA BLOOD LEVELS & SAID TO BE OF VALUE IN OVERCOMING

FATIGUE. ... DOSAGE: GIVEN ORALLY OR AS FEED ADDITIVE AGAINST STRESS INDUCED HIGH BLOOD

AMMONIA LEVELS IN POULTRY & AGAINST AMMONIA INTOXICATED RATS. /ASPARTIC ACID/Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 28

Parenteral nutrition


1985 to Present., p. VA2 84

/EXPL/: L-aspartate is a glycogenic amino acid, and it can also promote energy production via its metabolism in the

Krebs cycle. These latter activities were the rationale for the claim that supplemental aspartate has an anti-fatigue effect

on skeletal muscle, a claim that was never confirmed. /L-aspartate/

Physicians Desk Reference (PDR) for Nutritional Supplements 1st ed, Medical Economics, Thomson Healthcare; Montvale, NJ

(2001) p.255

There are claims that L-aspartate is a special type of mineral transporter for cations, such as magnesium, into cells.

Magnesium aspartate has not been found to be more biologically effective when compared with other magnesium salts.

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise

and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt,

spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been

hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in

the Krebs cycle and for stimulating the purine nucleotide cycle. An animal study using injected aspartate failed to find any

evidence of a glycogen-sparing effect or any ergogenic effects whatsoever. A more recent double-blind human study of

male weight trainers similarly found aspartate supplementation to have no effect, and another study of the effect ofaspartate on short intensive exercise again found no effect. /L-aspartate/


(2001) p.254

In 21 patients with ventricular arrhythmias we analysed the effect of an intravenous infusion of potassium-magnesium-

aspartate. It could be demonstrated that the frequency of ventricular ectopic beats significantly declined 1 hour after

starting the medication. The maximum effect occurred at the 6th and 7th hour and continued until the 10th hour after

starting the medication. /Potassium magnesium aspartate/ Abstract: PubMed

Kuhn P et al; Wien Med Wochenschr 141 (3): 64-5 (1991)

According to the hypothesis implying that the main reason of physical dependence on opiate is the inhibition of brain

L-asparaginase activity and L-aspartic acid gradually decreases compulsory opiate intake so that physical dependence

disappears by itself, 31 opiate addicts were given 8 g L-aspartic acid for 7 days after withdrawal from opiate and

appearance of abstinence syndrome signs. The attenuations by L-aspartic acid of the abstinence syndrome signs were

statistically compared with those obtained from other 12 opiate addicts received daily 50 mg chlorpromazine + 60 mg

diazepam which have long been used to suppress abstinence syndrome because of their multiple receptor blocking and

sedative effects. The intensity and duration of 13 signs out of 16 ones were found to be significantly more alleviated and

shortened in the addicts treated with L-aspartic acid. Abstract: PubMed

Sener AI et al; Arzneimittelforschung 36 (11): 1684-6 (1986)

7.1 Therapeutic Uses


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Mild gastrointestinal side effects including diarrhea have been reported. /L-aspartate/


(2001) p.255

Because of lack of long-term safety studies, L-aspartate salts should be avoided by children, pregnant women and

lactating women. /L-Aspartate/


(2001) p.255

The effects of oral administration of potassium and magnesium aspartate (K + Mg Asp) on physiologic responses to 90

min of treadmill walking at approximately 62% VO2 max were evaluated in seven healthy males (VO2 max = 59.5 ml X

kg-1 X min-1). A total of 7.2 g of K + Mg Asp were administered to each subject during a 24 h period prior to work and

compared to control and placebo trials. For control, placebo, and K + Mg Asp trials, no significant differences were

observed in resting or exercise values for ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2),

respiratory exchange ratio (RO), heart rate (HR), or blood pressure (BP). In addition, there were no differences between

the three trials for exercise-induced decreases in body weight and increases in rectal temperature, or for pre- and

post-exercise alterations in serum lactic acid, creatine kinase, lactic dehydrogenase, and percentage change in plasma

volume. The findings from this study indicate that oral ingestion of K+ Mg Asp prior to exercise had no effect on

cardiorespiratory, hematologic, and metabolic responses to 90 min of work conducted at approximately 62% VO2 max.

/Potassium magnesium aspartate/ Abstract: PubMed

Hagan RD et al; Int J Sports Med 3 (3): 177-81 (1982)

This study examined the effects of aspartate supplementation (ASP) on plasma ammonia concentrations (NH4+) during

and after a resistance training workout (RTW). Twelve male weight trainers were randomly administered ASP or vitamin

C in a crossover, double blind protocol, each trial separated by 1 wk. ASP and vitamin C were given over a 2 hr periodbeginning 5 hr prior to the RTW. The RTW consisted of bench, incline, shoulder, and triceps presses, and biceps curls at

70% of one repetition maximum (1-RM). After the RTW a bench press test (BPT) to failure at 65% of 1-RM was used to

assess performance. (NH4+) was determined preexercise, 20 and 40 min midworkout, immediately postexercise, and 15

min postexercise. Treatment-by-time ANOVAs, paired t tests, and contrast comparisons were used to identify mean

differences. No significant differences were observed between treatments for (NH4+) or BPT. (NH4+) increased

significantly from Pre to immediately postexercise for both the ASP and vitamin C trials. Acute ASP supplementation

does not reduce (NH4+) during and after a high intensity RTW in weight trained subjects. /Potassium magnesium

aspartate/ Abstract: PubMed

Tuttle JL et al; Int J Sport Nutr 5 (2): 102-9 (1995)

7.2 Drug Warning


There is no support for the claim that aspartates are exercise performance enhancers, i.e. ergogenic aids.

7.3 Drug Indication


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8 Pharmacology and Biochemistry


L-aspartate is considered a non-essential amino acid, meaning that, under normal physiological conditions, sufficient

amounts of the amino acid are synthesized in the body to meet the body's requirements. L-aspartate is formed by the

transamination of the Krebs cycle intermediate oxaloacetate. The amino acid serves as a precursor for synthesis ofproteins, oligopeptides, purines, pyrimidines, nucleic acids and L-arginine. L-aspartate is a glycogenic amino acid, and it

can also promote energy production via its metabolism in the Krebs cycle. These latter activities were the rationale for

the claim that supplemental aspartate has an anti-fatigue effect on skeletal muscle, a claim that was never confirmed.

8.1 Pharmacology





ASPARTIC ACID PLASMA CONCN WAS ELEVATED 30 MIN AFTER 1 G/KG L-ASPARTATE (ORAL OR IP) TO 15

DAY OLD & ADULT MICE. THEREAFTER, CONCN DECLINED EXPONENTIALLY WITH T/2 OF 0.2 HR IN BOTH.

PLASMA CONCN NOT APPRECIABLY ALTERED BY 10 & 100 MG/KG L-ASPARTATE ORAL OR IP ADMIN.

OPPERMANN ET AL; J ENVIRON PATHOL TOXICOL 2(4) 987 (1979)

Following ingestion, L-aspartate is absorbed from the small intestine by an active transport process. Following

absorption, L-aspartate enters the portal circulation and from there is transported to the liver, where much of it is

metabolized to protein, purines, pyrimidines and L-arginine, and is catabolized as well. L-aspartate is not metabolized in

the liver; it enters the systemic circulation, which distributes it to various tissues of the body. The cations associated with

L-aspartate independently interact with various substances in the body and participate in various physiological

processes. /L-aspartate/


(2001) p.254

... Contents of D- and L-aspartic acids in rats at different stages of growth (from 1 day before birth to 90 days after birth)

were determined. D-Aspartic acid was detected in all the brain tissue samples tested, but at different levels. In the

cerebrum of rats 1 day before birth, D-aspartic acid was found to be at the highest concentration of 81 nmol/g wet tissue.

The level of D-aspartic acid in rat brain falls rapidly after birth, while the L-aspartic acid level increases with age.

Abstract: PubMed

Zhao S et al; J Chromatogr B Biomed Sci Appl 762 (1): 97-101 (2001)

Enzymatic synthesis of 11C-(4)-L-aspartic acid was undertaken using commercially available wheat germ

phosphoenolpyruvate carboxylase. Whole-body distribution of the radioactive compound in rats showed higher

accumulation in the salivary gland, glandular stomach and the pancreas, as well as in the lungs. Within 60 minutes after

intravenous injection of 11C-(4)-L-aspartic acid, about 60% is removed as 11CO2 by expiration, indicating that the

carbon atom at the fourth position of the radioactive compound is easily subjected to decarboxylation. Abstract: PubMed

Nakamura T et al; Radioisotopes 33 (6): 363-9 (1984)

The brain efflux index method has been used to clarify the mechanism of efflux transport of acidic amino acids such as

L-aspartic acid (L-Asp), L-glutamic acid (L-Glu), and D-aspartic acid (D-Asp) across the blood-brain barrier (BBB). About

85% of L-[3H]Asp and 40% of L-(3H)Glu was eliminated from the ipsilateral cerebrum within, respectively, 10 and 20 min

of microinjection into the brain. The efflux rate constant of L-(3H)Asp and L-(3H)Glu was 0.207 and 0.0346 min(-1),

respectively. However, D-(3H)Asp was not eliminated from brain over a 20-min period. The efflux of L-(3H)Asp and

L-(3H)Glu was inhibited in the presence of excess unlabeled L-Asp and L-Glu, whereas D-Asp did not inhibit either form

8.2 Absorption, Distribution and Excretion


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of efflux transport. Aspartic acid efflux across the BBB appears to be stereospecific. Using a combination of TLC and the

bioimaging analysis, attempts were made to detect the metabolites of L-(3H)Asp and L-(3H)Glu in the ipsilateral

cerebrum and jugular vein plasma following a microinjection into parietal cortex, area 2. Significant amounts of intact

L-(3H)Asp and L-(3H)Glu were found in all samples examined, including jugular vein plasma, providing direct evidence

that at least a part of the L-Asp and L-Glu in the brain interstitial fluid is transported across the BBB in the intact form. To

compare the transport of acidic amino acids using brain parenchymal cells, brain slice uptake studies were performed.

Although the slice-to-medium ratio of D-(3H)Asp was the highest, followed by L-[3H]Glu and L-[3H]Asp, the initial uptake

rate did not differ for both L-(3H)Asp and D-(3H)Asp, suggesting that the uptake of aspartic acid in brain parenchymal

cells is not stereospecific. These results provide evidence that the BBB may act as an efflux pump for L-Asp and L-Glu to

reduce the brain interstitial fluid concentration and act as a static wall for D-Asp. Abstract: PubMed

Hosoya K et al; J Neurochem 73 (3): 1206-11 (1999)

Absorption

Absorbed from the small intestine by an active transport process





FOR L-ASPARTIC ACID, OXALOACETIC ACID IS PRODUCT OF OXIDATIVE DEAMINATION OR

TRANSAMINATION; ALPHA-ALANINE IS PRODUCT OF DECARBOXYLATION. /FROM TABLE/



METABOLIC PATHWAYS & PRODUCTS /IN ANIMAL BODY/: ASPARTIC ACID + CARBAMYLPHOSPHATE

/PRODUCE/ PHOSPHORUS + CARBAMYLASPARTIC ACID GIVE PYRIMIDINES; ASPARTIC ACID /PRODUCES/

FUMARIC ACID + NH3; ASPARTIC ACID /PRODUCES/ ASPARTIC SEMIALDEHYDE /PRODUCES/ HOMOSERINE

/PRODUCES/ (I) THREONINE, (II) METHIONINE, OR (III) LYSINE... /FROM TABLE/



METABOLIC PATHWAYS & PRODUCTS /IN ANIMAL BODY/: ASPARTIC ACID GIVES NITROGEN OF PURINE

RING...ASPARTIC ACID + IMP GIVE ADENYLOSUCCINATE GIVES AMP + FUMARATE... /FROM TABLE/



Following ingestion, L-aspartate is absorbed from the small intestine by an active transport process. Following

absorption, L-aspartate enters the portal circulation and from there is transported to the liver, where much of it is

metabolized to protein, purines, pyrimidines and L-arginine, and is catabolized as well. D-aspartate is not metabolized in

the liver; it enters the systemic circulation, which distributes it to various tissues of the body. The cations associated with

L-aspartate independently interact with various substances in the body and participate in various physiological

processes. /L-aspartate; D-aspartate/


(2001) p.254

8.3 Metabolism/Metabolites

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise

8.4 Mechanism of Action


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and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt,

spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been

hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in

the Krebs cycle and for stimulating the purine nucleotide cycle.


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9 Use and Manufacturing




Hydrolysis of asparagine, reaction of ammonia with diethyl fumarate

Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p.

100

L-Aspartic acid is industrially manufactured by an enzymatic process in which aspartase (l-aspartate ammonia lyase, EC

4.3.1.1) catalyzes the addition of ammonia to fumaric acid. Advantages of the enzymatic production method are higher

product concentration and productivity and the formation of fewer byproducts. Thus, l-aspartic acid can be easily

separated from the reaction mixture by crystallization.

Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co.

2003 to Present, p. V2 470 (2003)

In 1973, an immobilized cell system based on Escherichia coli cells entrapped in polyacrylamide gel lattice was

introduced for large-scale production.Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co.

2003 to Present, p. V2 470 (2003)

9.1 Methods of Manufacturing





(VET) COMMERCIALLY AVAILABLE AS MIXT OF POTASSIUM & MAGNESIUM ASPARTATES= SPARTASE.

/ASPARTIC ACID/

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 28

AVAILABLE COMMERCIALLY AS D(-)-, L(+)-, & DL-ASPARTIC ACID. /ASPARTIC ACID/

Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p.

100

150 G ASPARTIC ACID WAS POLYMERIZED IN PRESENCE OF H3PO4 TO GIVE 150 G

POLY(DEHYDROASPARTIC ACID) WHICH WAS TREATED WITH MORPHOLINE. POLYMER WAS INCORPORATED

INTO AN ANIONIC SHAMPOO WITH 4% CONCN.

JACQUET ET AL; POLY(ASPARTIC ACID AMIDES) USEFUL IN COSMETIC PREPN; FR DEMANDE PATENT 2424292

11/23/79 (OREAL SA)

USP and FCC grades; 99% min grade

Kuney, J.H., J.M. Mullican (eds.). Chemcyclopedia. Washington, DC: American Chemical Society, 1994., p. 258

9.2 Formulations/Preparations

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or

imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update

9.3 U.S. Production


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Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program on (L)-Aspartic Acid

(56-84-8). Available from, as of November 16, 2006: http://www.epa.gov/hpv/pubs/general/opptsrch.htm

(1992) No data

United States International Trade Commission. Synthetic Organic Chemicals - United States Production and Sales, 1992. USITC

Publication 2720, Feb. 1994 Washington, D.C.: United States Trade Commission, 1994., p. 3-139

World market for L-aspartic acid in 1982: 450 tonnes; in 1984: 250 tonnes


1985 to Present., p. VA2 90

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.

Year Production Range (pounds)

1986 10,000 - 500,000

1990 No Reports

1994 >10 million - 50 million

1998 10,000 - 500,000

2002 No Reports

US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002

Inventory Update Rule (IUR). L-Aspartic acid (56-84-8). Available from, as of November 7, 2006: http://www.epa.gov/oppt/iur

/tools/data/2002-vol.html




MANOMETRIC DETERMINATION OF L-ASPARTIC ACID, IN PROTEINS.

Bergmeyer, H.W. (ed.). Methods of Enzymatic Analysis. 2nd English ed. New York City: Academic Press, 1974., p. 1662

AMINO ACID ANALYZER, GLC.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing

Co., 1975., p. 633

AOAC method 960.47, Amino Acids in Vitamin Preparations; microbiological method using basal media /Amino acids/

Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC:

Association of Analytical Chemists, 1990, p. 1087

The following methods have been developed for the analysis of free amino acids in blood, food, and feedstocks: (1)

Protein hydrolysis, (2) Chromatographic methods that include high performance liquid chromatography (HPLC), gas

chromatography (GC) and thin-layer chromatography (TLC), (3) Colorimetric and Fluorimetric Analysis, (4) Spectrometric

Analysis, and (5) Enzymatic Determination and Microbial Assay /Amino acids/

Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p.

V2 531-4

9.4 Analytic Laboratory Methods


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Analyte: L-aspartic acid; matrix: chemical identification; procedure: infrared absorption spectrophotometry with

comparison to standards

U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S.

Pharmacopeial Convention, Inc., p196 (2006)

Analyte: L-aspartic acid; matrix: chemical purity; procedure: dissolution in water; addition of bromothymol blue indicator;

titration with sodium hydroxide until color changes from yellow to blueU.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S.

Pharmacopeial Convention, Inc., p196 (2006)

Analyte: aspartic acid; matrix: tissue (oocyte); procedure: high-performance liquid chromatography with ultraviolet

detection at 254 nm

O'Connor CM; Mol Reprod Dev 39: 392-396 (1994). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes

2-4. New York, NY: John Wiley & Sons, 2000, p.300

Analyte: aspartic acid; matrix: tissue (nervous system); procedure: high-performance liquid chromatography with

fluorescence detection; limit of detection:


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reversed-phase high-performance liquid chromatography with ultraviolet detection at 436 nm; limit of detection: 0.12-0.52

pmole

Krause L et al; J Chromatogr A 715: 67-79 (1995). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes

2-4. New York, NY: John Wiley & Sons, 2000, p.221

Analyte: aspartic acid; matrix: blood (plasma), protein; procedure: high-performance liquid chromatography with

fluorescence detection and ultraviolet detection at 263 nm; limit of detection: 50 fmole

Haynes PA et al; J Chromatogr 588: 107-114 (1991). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes2-4. New York, NY: John Wiley & Sons, 2000, p.223

Analyte: aspartic acid; matrix: blood (serum), urine; procedure: high-performance liquid chromatography with

electrochemical detection

Sherwood RA et al; J Chromatogr 528: 293-303 (1990). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis.

Volumes 2-4. New York, NY: John Wiley & Sons, 2000, p.225

Analyte: aspartic acid; matrix: food (cheese); procedure: high-performance liquid chromatography with ultraviolet

detection at 214 nm

Roturier JM et al; J Chromatogr A 696: 209-217 (1995). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis.Volumes 2-4. New York, NY: John Wiley & Sons, 2000, p.235

Analyte: aspartic acid; matrix: amniotic fluid, blood (plasma), cerebrospinal fluid, urine; procedure: high-performance

liquid chromatography with ultraviolet detection at 254 nm

Davey JR, Ersser RS; J Chromatogr 528: 9-23 (1990). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis.

Volumes 2-4. New York, NY: John Wiley & Sons, 2000, p.207

Analyte: aspartic acid; matrix: beverage (wine); procedure: high-performance liquid chromatography with fluorescence

detection; limit of detection: 2 microM

Kato M et al; Biomed Chromatogr 9: 193-194 (1995). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes2-4. New York, NY: John Wiley & Sons, 2000, p.209


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10 Safety and Hazards

10.1 Hazards Identification


10.1.1 GHS Classification

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Combustible.

10.1.2 Fire Hazard


Finely dispersed particles form explosive mixtures in air.

10.1.3 Explosion Hazard

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Cough. Sore throat.

10.1.4 Inhalation Hazard

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Redness. Pain.

10.1.5 Eye Hazard


Burning sensation in the throat and chest.

10.1.6 Ingestion Hazard

10.2 Safety and Hazard Properties

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Dust explosion possible if in powder or granular form, mixed with air. If dry, it can be charged electrostatically by swirling,pneumatic transport, pouring, etc.

10.2.1 Physical Danger


Decomposes on burning. This produces toxic gases including nitrogen oxides. Reacts violently with oxidants.

10.2.2 Chemical Danger

10.2.3 Occupational Exposure Limits


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from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439TLV (NOT-ESTABLISHED):.


Evaporation at 20C is negligible; a nuisance-causing concentration of airborne particles can, however, be reached

quickly when dispersed, especially if powdered.

10.2.4 Inhalation Risk


The substance is irritating to the eyes and respiratory tract.

10.2.5 Effects of Short Term Exposure

10.3 First Aid Measures


In case of fire in the surroundings, use appropriate extinguishing media.

10.3.1 Fire First Aid


Fresh air, rest. Refer for medical attention.

10.3.2 Inhalation First Aid


Remove contaminated clothes. Rinse and then wash skin with water and soap.

10.3.3 Skin First Aid


First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical

attention.

10.3.4 Eye First Aid


Rinse mouth. Do NOT induce vomiting. Give one or two glasses of water to drink.

10.3.5 Ingestion First Aid

10.4 Accidental Release Measures

Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Wash away remainder

with plenty of water. Personal protection: particulate filter respirator adapted to the airborne concentration of the

10.4.1 Spillage Disposal


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substance.


SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to

significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with

environmental regulatory agencies for guidance on acceptable disposal practices.

10.4.2 Disposal Methods

10.5 Handling and Storage

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Separated from strong oxidants.

10.5.1 Safety Storage

10.6 Exposure Control and Personal Protection

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439NO open flames.

10.6.1 Fire Prevention


Prevent build-up of electrostatic charges (e.g., by grounding). Closed system, ventilation, explosion-proof electrical

equipment and lighting. Prevent deposition of dust.

10.6.2 Explosion Prevention

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439PREVENT DISPERSION OF DUST!

10.6.3 Exposure Prevention


Use local exhaust or breathing protection.

10.6.4 Inhalation Prevention

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Protective gloves.

10.6.5 Skin Prevention

from ILO-ICSC [28] http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=1439Wear safety spectacles.

10.6.6 Eye Prevention


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Do not eat, drink, or smoke during work.

10.6.7 Ingestion Prevention

10.7 Transport Information


10.7.1 Packaging and Labelling


10.7.2 EC Classification


10.7.3 UN Classification

10.8 Regulatory Information


L-Aspartic acid is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantityof the substance added to food does not exceed the amount reasonably required to accomplish its intended physical,

nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food

grade and is prepared and handled as a food ingredient.

21 CFR 172.320; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from,

as of August 30, 2006: http://www.gpoaccess.gov/ecfr

10.8.1 FDA Requirements


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11 Toxicity

11.1 Toxicological Information


The substance can be absorbed into the body by ingestion.

11.1.1 Exposure Routes




ASPARTIC ACID PREVENTED TO SOME EXTENT THE APPEARANCE OF SYMPTOMS OF PHYSICAL MORPHINE

DEPENDENCE IN BALB/C MICE.

EROGLU L, H KOYUNCUOGLU; POL J PHARMACOL PHARM 31(2) 83 (1979)

The effects of amino acids on the embryotoxicity and placental transfer of nickel chloride, day 10 rat embryos were

cultured in rat serum medium containing nickel chloride or NiCl2-63 (0.34 or 0.68 uM NiCl with or without L-histidine (2

uM), L-aspartic acid, glycine (2 or 8 uM) or L-cysteine (2 uM). After 26 hr, conceptuses were assessed for survival,

growth and development and malformations. The nickel-63 contents of embryos and yolk sacs and the extent of

Nickel-63 binding to the proteins of the culture medium were also determined. Nickel chloride alone did not affect the

embryonic development at 0.34 uM and caused growth retardation and brain and caudal abnormalities at 0.68 uM.

Coincubation of L-histidine, L-cysteine, or L-aspartic acid 0.68 uM Ni reduced the growth retardation and the incidence

and/or severity of brain defects caused by nickel chloride and decreased the concentrations of nickel-63 in the yolk sacs

compared to 0.68 uM nickel-63 alone. In the presence of L-histidine, L-cysteine or L-aspartic acid there was a shift of

nickel-63 binding from the high molecular weight proteins of the culture medium to the low molecular weight fraction.

Abstract: PubMed

Saillenfait AM et al; Toxicol Appl Pharmacol 123 (2): 299-308 (1993)

The effect of oral D-aspartic acid and/or L-aspartic acid (aspartic acid) on the body weight of rats was studied. Rats given

the D- or D- plus L-isomers showed a greater decrease in weight and in protein, triglyceride and glycogen than did rats

given the L-isomer alone. The results were discussed with reference to amino acid antagonism of opioids.

Koyuncuoglu H et al; Arzneim. Forsch 32 (7): 738-741 (1982)

11.1.2 Interactions


ToxicityMild gastrointestinal side effects including diarrhea. LD (rat) > 5,000 mg/kg.

11.1.3 Toxicity Summary

50

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if

necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by

nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and

treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with

11.1.4 Antidote and Emergency Treatment


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water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse

mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and

does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier

Mosby, St. Louis, MO 2005, p. 160

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is

unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques

with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering

a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as

necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated

Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously.

Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to

assist eye irrigation ... . /Poisons A and B/

Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier

Mosby, St. Louis, MO 2005, p. 160-1




/LABORATORY ANIMALS: Neurotoxicity/ The effect of L-aspartic acid, L-asparagine and/or L-asparaginase were

compared with those of imipramine on immobility, number of defecations, increase of nociceptive threshold, and

hypothermia, induced by forced swimming in rats. L-Aspartic acid was found to be as effective as imipramine in reducing

the effects of forced swimming, presumable by normalizing the decreased level of endogenous L-aspartic acid, due to

the inhibition of L-asparaginase activity and/or by stimulating the inhibited enzyme. The other treatments antagonized the

immobility, but not the increased number of defecations. All compounds abolished the elevation of nociceptive threshold

and hypothermia. Abstract: PubMed

Koyuncuoglu H et al; Experientia 38 (1): 117-8 (1982)

/OTHER TOXICITY INFORMATION/ Aspartate ... when administered to young rodents in large dosage alters the ERG/electroretinogram/ and causes wide spread histologically demonstrable injury to the retina. In amphibians, aspartate

interferes with protein synthesis by the retina, and suppresses electrical activity of the retina, though leaving the

response of photoreceptors unaffected.

Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 121

/OTHER TOXICITY INFORMATION/ EXCESSIVE LEVELS PARENTERALLY PRODUCE VOMITING.

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 28

/OTHER TOXICITY INFORMATION/ Taste aversions to either monosodium glutamate, L-aspartic acid or N-methyl-

D-aspartate were produced by injecting rats with LiCl after they had ingested one of these stimuli. Subsequently, rats

were tested to determine whether they would ingest any of the above compounds. The results clearly show that a

conditioned aversion to monosodium glutamate generalized to L-aspartic acid in a dose-dependent manner. Conversely,

rats conditioned to avoid L-aspartic acid also avoided monosodium glutamate. Conditioned aversions to monosodium

glutamate or L-aspartic acid generalized to sucrose when amiloride was included in all solutions. Importantly, aversions

to monosodium glutamate or L-aspartic acid did not generalize to N-methyl-D-aspartate, NaCl or KCl, and aversions to

N-methyl-D-aspartate did not generalize to monosodium glutamate, L-aspartic acid, sucrose or KCl. These data indicate

that rats perceive monosodium glutamate and L-aspartic acid as similar tastes, whereas N-methyl-D-aspartate, NaCl and

KCl elicit other tastes. The results do not support a dominant role for the N-methyl-D-aspartate subtype of glutamate

receptors in taste transduction for MSG (i.e. umami) in rats. Abstract: PubMed

11.1.5 Non-Human Toxicity Excerpts


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Stapleton JR et al; Chem. Senses 24: 449-457 (1999)

11.2 Ecological Information


L-Aspartic acid's production and use as a roborant and as a raw material in the synthesis of peptide drugs and, as the

DL-aspartic acid mixture, used in biological and clinical studies, preparation of culture media, an organic intermediate, an

ingredient of aspartame, detergents, fungicides, germicides, and in metal complexation may result in its release to the

environment through various waste streams. In addition, L-aspartic acid, as the DL-aspartic acid mixture, is a naturally-

occurring non-essential amino acid and is found in both plants and animals. If released to air, an estimated vapor

pressure of 2.6X10-7 mm Hg at 25 deg C indicates L-aspartic acid will exist in both the vapor and particulate phases in

the atmosphere. Vapor-phase L-aspartic acid will be degraded in the atmosphere by reaction with photochemically-

produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 10 hours. Particulate-phase L-aspartic

acid will be removed from the atmosphere by wet or dry deposition. L-Aspartic acid does not contain chromophores that

absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If

released to soil, L-aspartic acid is expected to have very high mobility based upon an estimated Koc of 39. The pKa

values for L-aspartic acid are 1.92 (COOH), 3.87 (COOH), and 9.87 (amine), indicating that this compound will exist as azwitterion in the environment. Volatilization from moist soil surfaces and from water surfaces is not expected to be an

important fate process because ionic compounds do not volatilize. L-Aspartic acid is not expected to volatilize from dry

soil surfaces based upon its vapor pressure. Based on results from several screening tests, L-aspartic acid is expected

to readily biodegrade under both aerobic and anaerobic conditions in soil and water environments. If released into water,

L-aspartic acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. An

estimated BCF of 0.7 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected

to be an important environmental fate process since this compound lacks functional groups that hydrolyze under

environmental conditions. Occupational exposure to L-aspartic acid may occur through inhalation of dust and dermal

contact with this compound at workplaces where L-aspartic acid is produced or used. L-Aspartic acid is a non-essential

amino acid which is naturally produced by both plants and animals. In addition, L-aspartic acid is ubiquitous in the diet of

the general public through the ingestion of both plants and meats. Intake of L-aspartic acid may be increased by the

additional use of nutritional supplements containing this compound by some individuals. (SRC)

11.2.1 Environmental Fate/Exposure Summary


Aspartic acid, as the DL mixture, is a naturally-occurring non-essential amino acid(1).

(1) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary, 14th ed. John Wiley & Sons, Inc.: New York, NY, p. 95 (2001)

11.2.2 Natural Occurring Sources


L-Aspartic acid's production and use as a roborant (1), a raw material in the synthesis of peptide drugs(2), and, as the

DL-aspartic acid mixture, used in biological and clinical studies, preparation of culture media, an organic intermediate, an

ingredient of aspartame, detergents, fungicides, germicides, and in metal complexation(3) may result in its release to the

environment through various waste streams(SRC).

(1) O'Neil MJ et al; The Merck Index. 13th ed., Merck & Co., Inc.: Whitehouse Station, NJ p. 143 (2001) (2) Ashford RD;

Ashford's Dictionary of Industrial Chemicals, Wavelength Publications Ltd: London, England p. 97 (1994) (3) Lewis RJ Sr;

Hawley's Condensed Chemical Dictionary, 14th ed. John Wiley & Sons, Inc.: New York, NY, p. 95 (2001)

11.2.3 Artificial Sources


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TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 39(SRC), determined from a

water solubility of 5,360 mg/L at 25 deg C(2) and a regression-derived equation(3), indicates that L-aspartic acid is

expected to have very high mobility in soil(SRC). L-Aspartic acid has pKa values of 1.92, 3.87, and 9.87 at 25 deg C(4)

indicating that L-aspartic acid will exist as a zwitterion in the environment. Volatilization of L-aspartic acid from moist soil

surfaces is not expected to be an important fate process(SRC) since ionic compounds do not volatilize. L-Aspartic acid is

not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-7 mm Hg at 25deg C(SRC), determined from a fragment constant method(5). Based on results from several screening tests, L-aspartic

acid is expected to readily biodegrade under both aerobic (6-10) and anaerobic(11) conditions(SRC).

(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC,

Boca Raton, FL, p. 105 (2003) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer

Chem Soc pp. 4-9 (1990) (4) Sergeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution, IUPAC

Chemical Data Series No. 2, New York, NY: Pergamon Press, p. 95 (1979) (5) Lyman WJ; p. 31 in Environmental Exposure

From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985) (6) Babeu L et al.; J Indust Microb 2: 107-15

(1987) (7) Takemoto S et al.; Suishitsu Odaku Kenkyu 4: 80-90 (1981) (8) Heukelekian H, Rand MC; J Water Pollut Contr Assoc,

27: 1040-53 (1955) (9) Helfgott TB et al; An Index of Refractory Organics, EPA-600/2-77-174. Ada, OK: U.S. EPA (1977) (10)

Malaney GW, Gerhold RM; J Water Pollut Control Fed, 41: R18-R33 (1969) (11) Stuckey DC, McCarty PL; Water Res 18:

1343-53 (1984)

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 39(SRC), determined from a water

solubility of 5,360 mg/L at 25 deg C(2) and a regression-derived equation(3), indicates that L-aspartic acid is not

expected to adsorb to suspended solids and sediment(SRC). Measured pKa values of 1.92, 3.87, and 9.87 at 25 deg

C(4) indicate that L-aspartic acid will exist as a zwitterion in the environment. Volatilization from water surfaces is not

expected because ionic compounds do not volatilize. According to a classification scheme(5), an estimated BCF of

0.7(SRC), from its water solubility(2) and a regression-derived equation(3), suggests the potential for bioconcentration in

aquatic organisms is low(SRC). The biodegradation of L-aspartic acid is expected to occur readily based on results from

both screening and grab sample tests. Relative rates of total utilization of 2.7, 1.5, and 0.10%/hr were measured over a

4-hour period in three samples of seawater(6). In aerobic screening tests, 38.7 to 80.5% BODT was reached in 5 days

using a sewage inoculum(7-9) while in an anaerobic screening test, 79% biodegradation was reported in 35 days(10).

(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC,Boca Raton, FL, p. 105 (2003) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer

Chem Soc pp. 4-9, 5-5 (1990) (4) Sergeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution, IUPAC

Chemical Data Series No. 2, New York, NY: Pergamon Press, p. 95 (1979) (5) Franke C et al; Chemosphere 29: 1501-14 (1994)

(6) Billen G et al; Estuarine Coastal Mar Sci 11:279-294 (1980) (7) Babeu L et al; J Indust Microb 2: 107-15 (1987) (8) Takemoto

S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981) (9) Heukelekian H, Rand MC; J Water Pollut Contr Assoc, 27: 1040-53 (1955)

(10) Stuckey DC, McCarty PL; Water Res 18: 1343-53 (1984)

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the

atmosphere(1), L-aspartic acid, which has an estimated vapor pressure of 2.6X10-7 mm Hg at 25 deg C(SRC),

determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the

ambient atmosphere. Vapor-phase L-aspartic acid is degraded in the atmosphere by reaction with photochemically-

produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 10 hours(SRC), calculated from itsrate constant of 4.0x10-11 cu cm/molecule-sec at 25 deg C(SRC) that was derived using a structure estimation

method(3). Particulate-phase L-aspartic acid may be removed from the air by wet or dry deposition(SRC). L-Aspartic

acid does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be

susceptible to direct photolysis by sunlight(4).

(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I,

Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985) (3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (4)

Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

11.2.4 Environmental Fate


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AEROBIC: The biodegradation of L-aspartic acid was measured in several BOD5 tests. After 5 days, 48.5%(1) 38.7(2)

and 80.5%(3) of the theoretical BOD was reached using a sewage inoculum. L-Aspartic acid was degraded by 81%

BODT after 30 days using a sewage inoculum(4). In a second Warburg test using an activated sludge inoculum, 8.9,

16.2, and 28.8% BODT was reached after 0.25, 0.5, and 1 day, respectively(5). DL-Aspartic acid was rapidly degraded

by 98 to >99% in a laboratory-scale activated sludge unit at initial concentrations of 599, 1198, 2396, and 4792 mg/L and

average detention times of 20.5, 29, 42, and 85 hours, respectively(6). Samples of marine water from the Scheldtestuary, the Belgian coastal zone of the North Sea, and the English Channel were incubated with 14C-labeled

DL-aspartic acid and relative rates of total utilization (incorporation plus respiration) of 2.7, 1.5, and 0.10%/hr,

respectively, were measured over a 4-hour period(7). Based on these data, L-aspartic acid is expected to biodegrade

rapidly.

(1) Babeu L et al; J Indust Microb 2: 107-15 (1987) (2) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981) (3)

Heukelekian H, Rand MC; J Water Pollut Contr Assoc, 27: 1040-53 (1955) (4) Helfgott TB et al; An Index of Refractory Organics,

EPA-600/2-77-174. Ada, OK: U.S. EPA (1977) (5) Malaney GW, Gerhold RM; J Water Pollut Control Fed, 41: R18-R33 (1969)

(6) Chudoba J et al; Sb VYS Sk Chem - Technol Praze, Technol Vody, 13: 45-63 (1968) (7) Billen G et al; Estuarine Coastal Mar

Sci 11: 279-294 (1980)

ANAEROBIC: The biodegradability of L-aspartic acid at 2 g/L was measured in the Biochemical Methane Potential assay

and incubated anaerobically at 35 and 55 deg C. After 35 and 78 days, 79 and 73% bioconversion to methane was

reported(1). The fermentation of L-aspartic acid proceeded through acetate and propionate(1).

(1) Stuckey DC, McCarty PL; Water Res 18: 1343-53 (1984)

11.2.5 Biodegredation



The rate constant for the vapor-phase reaction of L-aspartic acid with photochemically-produced hydroxyl radicals has

been estimated as 4.0X10-11 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This

corresponds to an atmospheric half-life of about 10 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals

per cu cm(1). L-Aspartic acid is not expected to undergo hydrolysis in the environment due to the lack of functionalgroups that hydrolyze under environmental conditions(2). L-Aspartic acid does not contain chromophores that absorb at

wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(2). Measured pKa

values of 1.92 (COOH), 3.87 (COOH), and 9.87 (amine) at 25 deg C(3) indicate that L-aspartic acid will exist as a

zwitterion in the environment.

(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (2) Lyman WJ et al; Handbook of Chemical Property Estimation

Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990) (3) Sergeant EP, Dempsey B; Ionisation constants of

organic acids in aqueous solution, IUPAC Chemical Data Series No. 2, New York, NY: Pergamon Press, p. 95 (1979)

The chlorination of aspartic acid at 10 mg/L by sodium hypochlorite produced 2.7 ug/L dichloroacetonitrile following a

60-minute incubation(1). Abstract: PubMed

(1) Ueno H et al; Chemosphere 33: 1425-33 (1996)

11.2.6 Abiotic Degredation

An estimated BCF of 0.7 was calculated in fish for L-aspartic acid(SRC), using a water solubility of 5,360 mg/L(1) and a

regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for

bioconcentration in aquatic organisms is low(SRC).

(1) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC, Boca Raton, FL, p. 105 (2003) (2) Lyman WJ et

11.2.7 Bioconcentration


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al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 5-5 (1990) (3) Franke C et al;

Chemosphere 29: 1501-14 (1994)


The Koc of L-aspartic acid is estimated as 39(SRC), using a water solubility of 5,360 mg/L(1) and a regression-derived

equation(2). According to a classification scheme(3), this estimated Koc value suggests that L-aspartic acid is expected

to have very high mobility in soil. However, L-aspartic acid has pKa values of 1.92, 3.87, and 9.87(5), indicating that this

compound will exist as a zwitterion in the environment. In H(Al) montmorillonite, aspartic acid showed an L-2 type

adsorption isotherm with an initial preferential sorption when compared with the solvent or other solutes followed by a

decrease in sorption as more solute was sorbed(4).

(1) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC, Boca Raton, FL, p. 105 (2003) (2) Lyman WJ et

al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990) (3) Swann RL et al;

Res Rev 85: 17-28 (1983) (4) Weber JB, Miller CT; in Reactions and Movement of Organic Chemicals in Soils, SSSA Special

Publication No. 22, p. 305-33 (1989) (5) Sergeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution,

IUPAC Chemical Data Series No. 2, New York, NY: Pergamon Press, p. 95 (1979)

11.2.8 Soil Adsorption/Mobility


Measured pKa values of 1.92, 3.87, and 9.87 at 25 deg C(1) indicate that L-aspartic acid will exist as a zwitterion in the

environment. Volatilization from moist soil surfaces and water surfaces will not occur as ionic compounds do not

volatilize. L-Aspartic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor

pressure of 2.6X10-7 mm Hg at 25 deg C(SRC), determined from a fragment constant method(2).

(1) Sergeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution, IUPAC Chemical Data Series No. 2,

New York, NY: Pergamon Press, p. 95 (1979) (2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB,

Blau GE, eds, Boca Raton, FL: CRC Press (1985)

11.2.9 Volatilization from Water/Soil




SURFACE WATER: Water samples collected on June 3, 1986 from the lower Tama River, Japan, a highly eutrophic

urban river, contained aspartic acid at concentrations of 0.66 to 1.09 umol/L(1).

(1) Ochiai M et al; Mar Chem 25: 265-78 (1988)

SEAWATER: Concentrations of DL-aspartic acid were measured at 3 marine locations representing an estuarine, a

coastal and an open sea environment during 1977-1978(1). DL-Aspartic acid concentrations ranged from 0.010 to 0.033

umol/L in water from the Scheldt estuary, from 0.019-0.031 umol/L in water collected from the Belgian coastal zone of

the North Sea, and from 0.010 to 0.10 umol/L in water collected from the English Channel(1).

(1) Billen G et al; Estuarine Coastal Mar Sci 11:279-294 (1980)

RAIN/SNOW/FOG: Aspartic acid was measured in 30 of 73 precipitation samples (range of


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SOIL: Aspartic acid was not detectable in soil samples collected from 3 depths at a landfill in Spain containing urban

wastes (detection limit not provided although measurements for other amino acids were provided in units of nmol/g)(1).

(1) Gonzalez-Vila FJ et al; Chemosphere 31: 2817-25 (1995)

SEDIMENT: A Fanning Island (Central Pacific Ocean)lagoon carbonate mud sediment contained aspartic acid at

concentrations of 10.68, 8.40, 4.14, 3.10, 2.60, 4.11 and 3.38 umol/g in grain size fractions of


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12 Literature

from PubChem [33]Depositor Provided PubMed Citation Count (15439)

12.1 Depositor Provided PubMed Citations

from PubChem [33]

12.2 NLM Curated PubMed Citations


Synthesis Reference

Nguyen-Cong Duc, "Method of making L-aspartic acid from fumaric acid." U.S. Patent US3933586, issued August, 1965.

12.3 Synthesis References

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13 Patents

from PubChem [33]

13.1 Depositor-Supplied Patent Identifiers

CLICK TO LOAD...


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14 Biomolecular Interactions and Pathways

from PubChem [33]

14.1 Protein Bound 3-D Structures

from PubChem [33]

14.2 Biosystems and Pathways

from DrugBank [3] http://www.drugbank.ca/drugs/DB00128#targets

1 of 24 DrugBank Interactions

Target Ribonuclease pancreatic

General Function Involved in nucleic acid binding

Specific Function Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidinenucleotides. Acts on single stranded and double stranded RNA

Gene Name RNASE1

GenBank Gene D26129

References

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN,

Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

Pubmed

14.3 DrugBank Interactions

CLICK TO LOAD...

CLICK TO LOAD...


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Target Lysozyme C

General Function Involved in retina homeostasis

Specific Function

Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids

are associated with the monocyte-macrophage system and enhance the activity of

immunoagents.

Gene Name LYZ

References

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN,

Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

Pubmed


Target Calcium-binding mitochondrial carrier protein Aralar2

General Function Involved in amino acid transport activity

Specific FunctionCalcium-dependent mitochondrial aspartate and glutamate carrier. May have a

function in the urea cycle

Gene Name SLC25A13

GenBank Gene AJ496569

GenBank Protein 22002963

References

Contreras L, Gomez-Puertas P, Iijima M, Kobayashi K, Saheki T, Satrustegui J:

Ca2+ Activation kinetics of the two aspartate-glutamate mitochondrial carriers,

aralar and citrin: role in the heart malate-aspartate NADH shuttle. J Biol Chem.2007 Mar 9;282(10):7098-106. Epub 2007 Jan 9. Pubmed

1.

Saheki T, Iijima M, Li MX, Kobayashi K, Horiuchi M, Ushikai M, Okumura F,

Meng XJ, Inoue I, Tajima A, Moriyama M, Eto K, Kadowaki T, Sinasac DS, Tsui

LC, Tsuji M, Okano A, Kobayashi T: Citrin/mitochondrial glycerol-3-phosphate

dehydrogenase double knock-out mice recapitulate features of human citrin

deficiency. J Biol Chem. 2007 Aug 24;282(34):25041-52. Epub 2007 Jun 25.

Pubmed

2.

Satrustegui J, Pardo B, Del Arco A: Mitochondrial transporters as novel targets

for intracellular calcium signaling. Physiol Rev. 2007 Jan;87(1):29-67. Pubmed

3.

Ikeda S: [Adult-onset citrullinemia] Brain Nerve. 2007 Jan;59(1):59-66. Pubmed4.

Ikeda S: [Adult-onset citrullinemia] No To Shinkei. 2007 Jan;59(1):59-66.

Pubmed

5.


Target Aspartate aminotransferase, cytoplasmic

General Function Amino acid transport and metabolism

Gene Name GOT1


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4 of 24 DrugBank

aspartic acid.pdf

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