It has been demonstrated that L-aspartic acid is an appropriate prodrug for colon-specific drug delivery[1]. Preadministration of 100 mM L-Aspartic acid and 100 mM L-Glu increases the amount of L-[3H]Asp that is still in the brain at 5 minutes by 206 and 178%, respectively; L-[3H]Asp efflux transport is unaffected by 100 mM D-Asp. The coadministration of 100 mM L-Aspartic acid and 100 mM L-Glu, respectively, increases that value for L-[3H]Glu at 20 minutes by 145 and 156%, but not by D-Asp. It's noteworthy to note that L-Aspartic acid appears to traverse the BBB seven times faster than L-Glu does[2].

Absorption, Distribution and Excretion
Absorbed from the small intestine by an active transport process
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.
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/
... 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.
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.
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 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.

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Metabolism / Metabolites
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/

Interactions
ASPARTIC ACID PREVENTED TO SOME EXTENT THE APPEARANCE OF SYMPTOMS OF PHYSICAL MORPHINE DEPENDENCE IN BALB/C MICE.
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.
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.

[1]. Blood-brain barrier produces significant efflux of L-aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method. J Neurochem. 1999 Sep;73(3):1206-11.

[2]. In vivo pharmacokinetic study for the assessment of poly(L-aspartic acid) as a drug carrier for colon-specific drug delivery. J Pharmacokinet Biopharm. 1995 Aug;23(4):397-406.

L-aspartic acid is the L-enantiomer of aspartic acid. It has a role as an Escherichia coli metabolite, a mouse metabolite and a neurotransmitter. It is an aspartate family amino acid, a proteinogenic amino acid, an aspartic acid and a L-alpha-amino acid. It is a conjugate acid of a L-aspartate(1-). It is an enantiomer of a D-aspartic acid.
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.
L-Aspartic acid is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Aspartic acid has been reported in Streptomyces akiyoshiensis, Pinus densiflora, and other organisms with data available.
Aspartic Acid is a non-essential amino acid in humans, Aspartic Acid has an overall negative charge and plays an important role in the synthesis of other amino acids and in the citric acid and urea cycles. Asparagine, arginine, lysine, methionine, isoleucine, and some nucleotides are synthesized from aspartic acid. Aspartic acid also serves as a neurotransmitter. (NCI04)
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.

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

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Mechanism of Action
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.

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Therapeutic Uses
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/
Parenteral nutrition
/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/
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 of aspartate on short intensive exercise again found no effect. /L-aspartate/
For more Therapeutic Uses (Complete) data for (L)-ASPARTIC ACID (6 total), please visit the HSDB record page.

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Drug Warnings
Mild gastrointestinal side effects including diarrhea have been reported. /L-aspartate/
Because of lack of long-term safety studies, L-aspartate salts should be avoided by children, pregnant women and lactating women. /L-Aspartate/
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/
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 period beginning 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/

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Pharmacodynamics
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 of proteins, 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.

C4H7NO4

133.1027

133.037

56-84-8

25608-40-6;1115-63-5 (mono-potassium salt);14007-45-5 (potassium salt);17090-93-6 (hydrochloride salt);2001-89-0 (di-potassium salt);2068-80-6 (magnesium (2:1) salt);21059-46-1 (calcium salt);3792-50-5 (mono-hydrochloride salt);39162-75-9 (calcium (2:1) salt);5598-53-8 (di-hydrochloride salt)

5960

White to off-white solid powder

1.5±0.1 g/cm3

264.1±30.0 °C at 760 mmHg

>300 °C (dec.)(lit.)

113.5±24.6 °C

0.0±1.1 mmHg at 25°C

1.531

-0.67

3

5

3

9

133

1

C([C@@H](C(=O)O)N)C(=O)O

CKLJMWTZIZZHCS-REOHCLBHSA-N

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

(2S)-2-aminobutanedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

1M NaOH : 100 mg/mL (~751.31 mM)
H2O : ~2 mg/mL (~15.03 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 1 mg/mL (7.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)