Plasma Aspartate Levels Research Articles

Lowered circulating aspartate is a metabolic feature of human breast cancer.

Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer.

Early clinical and laboratory indicators of acute dengue illness.

A prospective observational study was conducted to identify early indicators of acute dengue virus infection. Children with fever for <72 h without obvious cause were studied at hospitals in Bangkok and Kamphaeng Phet, Thailand, until resolution of fever. Of 172 evaluable subjects (91% of enrollees), 60 (35%) had dengue, including 32 with dengue fever (DF) and 28 with dengue hemorrhagic fever (DHF). At enrollment, children with dengue were more likely than children with other febrile illnesses (OFI) to report anorexia, nausea, and vomiting and to have a positive tourniquet test, and they had lower total white blood cell counts, absolute neutrophil and absolute monocyte counts, and higher plasma alanine and aspartate (AST) aminotransferase levels than children with OFI. Plasma AST levels were higher in children who developed DHF than in those with DF. These data identify simple clinical and laboratory parameters that help to identify children with DF or DHF.

Effect of Carbohydrate Ingestion on Plasma Aspartate Concentrations in Infant Mice Administered Sodium L-Aspartate

Previous studies of infant pigs have demonstrated that simultaneous ingestion of carbohydrate (1 g/kg body weight) and glutamate (300 mg/kg body weight) resulted in markedly lower mean peak plasma glutamate concentration and a smaller area under the plasma glutamate concentration-time curve (AUC) than ingestion of the equivalent amount of glutamate alone. This study was carried out to investigate whether a similar carbohydrate-induced effect occurred with the other dicarboxylic amino acid, aspartate. Eight-day-old mice were administered sodium L-aspartate at 250, 500 and 1000 mg/kg body weight with and without 1.0 g/kg body weight of partially hydrolyzed cornstarch. Mean peak plasma aspartate concentration and plasma aspartate AUC values increased in proportion to the aspartate dose. The addition of carbohydrate to the aspartate solution had no significant effect on either mean peak plasma aspartate concentrations or AUC values at aspartate doses of 250 and 500 mg/kg body weight. A modest, but significant effect of carbohydrate was noted on the mean peak plasma aspartate levels in animals administered 1000 mg/kg body weight aspartate (P < 0.05, Student’s t-test). However, analysis of variance showed no significant carbohydrate effect and plasma AUC values were not significiantly affected. These data indicate that carbohydrate affects the metabolism of aspartate and glutamate differently.

Effect of an Abuse Dose of Aspartame upon Plasma and Erythrocyte Levels of Amino Acids in Phenylketonuric Heterozygous and Normal Adults

Plasma and erythrocyte levels of free amino acids were measured in five female subjects known to be heterozygous for phenylketonuria and six subjects assumed to be normal (three male, three female) who were administered an abuse dose of aspartame (100 mg/kg) in orange juice. Small increases in plasma aspartate levels were noted 30 minutes after aspartame loading in both groups, with mean (+/- SD) levels increasing from 0.15 +/- 0.05 mumoles/100 ml to 0.43 +/- 0.23 mumoles/100 ml in normal subjects (P = 0.02), and from 0.49 +/- 0.23 mumoles/100 ml to 0.80 +/- 0.56 mumoles/100 ml in heterozygous subjects (P > 0.05). However, plasma aspartate levels remained within normal postprandial levels in each case. Erythrocyte aspartate levels were unchanged in both groups. In normal subjects, plasma phenylalanine levels (mean +/- SD) increased from fasting levels (5.40 +/- 1.05 mumoles/100 ml) to mean peak values of 20.2 +/- 6.77 mumoles/100 ml. In heterozygous subjects, mean peak plasma phenylalanine levels were approximately twice as high (41.7 +/- 2.33 mumoles/100 ml), and the area under the plasma concentration-time curve twice as large. Peak plasma phenylalanine levels, however, were below those associated with toxic effects. The data indicate slower, but adequate metabolism and clearance of an abuse dose of aspartame by the phenylketonuric heterozygote.

Plasma and erythrocyte amino acid levels of adult humans given 100 mg/kg body weight aspartame

Blood amino acid and methanol levels were measured in 6 fasting adult subjects (3 male, 3 female) administered an abuse dose of aspartame (100 mg/kg body wt) in both solution and slurry form. A randomized cross-over design was used. Greater variation in blood aspartate, phenylalanine and methanol levels was noted when aspartame was administered in slurry form. Blood aspartate, phenylalanine and methanol levels did not exceed those associated with toxic findings in any case. Plasma aspartate levels increased from mean (± S.D.) baseline levels of 0.16 ± 0.05 μmol/dl to peak values of 0.43 ± 0.23 ( P = 0.02) 30 min after administration in solution. Plasma aspartate levels increased to peak values of 3.6 and 5.8 μmol/dl at 30–45 min in 2 of 6 subjects given aspartame in slurry form, while levels in the other 4 subjects were unchanged from baseline values. Erythrocyte aspartate levels were unchanged in all subjects. Plasma and erythrocyte phenylalanine levels increased significantly ( P = 0.001) after both solution and slurry administration. Plasma phenylalanine levels reached mean (± S.D.) peak values of 20.3 ± 2.05 and 26.0 ± 18.9 μmol/dl respectively 45 min after loading. The higher variation after slurry administration reflected 2 subjects with peak values of 45.8 and 51.3 μmol/dl. Blood methanol levels increased after both solution and slurry administration, reaching mean (± S.D.) levels of 1.16 ± 0.47 and 1.27 ± 0.48 mg/dl respectively 60–90 min after loading.

Placental transfer of aspartate and its metabolites in the primate

The placental transfer of aspartate was tested in pregnant monkeys infused maternally with sodium aspartate. In five animals infused at 100 mg/kg/hr, maternal plasma aspartate levels increased from 0.36 ± 0.19 to 80.2 ± 11.5 μmole/dl (mean ± SD). However, fetal plasma aspartate levels increased only slightly from 0.42 ± 0.31 to 0.98 ± 0.24 μmole/dl ( p = 0.02). Erythrocyte aspartate levels were unchanged in both fetal and maternal circulation. In two animals infused at 200 mg/kg/hr, maternal plasma aspartate levels increased from 0.28 and 0.31 μmole/dl to values of 141 and 237 μmole/dl, respectively. This increase produced a significant ( p = 0.001) increase in fetal plasma aspartate levels from 0.53 and 0.67 to 3.3 and 4.5 μmole/dl, respectively. Maternal plasma aspartate levels in two animals infused at 400 mg/kg/hr increased from 0.5 and 0.7 μmole/dl to 400 and 750 μmole/dl, respectively, at the end of the infusion. Fetal plasma aspartate levels increased from 0.21 and 0.25 μmole/dl to 60 and 92 μmole/dl, respectively. Maternal aspartate infusion at each level increased maternal, but not fetal, plasma taurine levels. The increase in maternal taurine levels was not in proportion to the dose of aspartate infused. Aspartate metabolites, glucose, and lactate were readily transferred across the placenta. The data indicate that aspartate, like glutamate but unlike most amino acids, is not concentrated toward the fetal circulation in the pregnant primate, and suggest that a barrier to aspartate transfer exists unless maternal plasma levels are grossly elevated.

Plasma aspartate levels in rats following administration of monopotassium aspartate via three routes.

Plasma aspartate levels were measured after potassium aspartate administration through different routes to rats of various ages. The changes in plasma levels were most significant with intraperitoneal injection. Dose- and age-related responses to aspartate load were obtained. The present data suggest that a marked elevation of plasma aspartate levels may result in neuronal necrosis. By comparing the plasma aspartate levels with the results on hypothalamic lesion (Okaniwa et al., 1979), plasma peak value associated with the lesion was estimated in each case of various administration routes and rat ages.

Absorption, utilization, and safety of aspartic acid.

The dicarboxylic amino acids, asparate and glutamate, occupy unique positions in intermediary metabolism, particularly in the mitochondria, where they play important roles in nitrogen and energy metabolism. Administration of large quantities of glutamate and asparate to the newborn mouse produces a variety of neurotoxic effects, the most marked of which is neuronal necrosis. Neurotoxic effects of glutamate and aspartate in animal species other than the rodent are highly controversial. In the most critical animal species, the infant subhuman primate, at least four research groups have failed to duplicate the original report of glutamate-induced neuronal necrosis. Marked elevations in plasma glutamate or aspartate must occur for development of neuronal necrosis. In the highly sensitive neonatal mouse, plasma glutamate plus plasma aspartate levels must reach 60-80 mumol/dl to produce even minimal neuronal necrosis. In the healthy neonatal primate, loads producing plasma glutamate levels ranging from 50 to 1,600 mumol/dl failed to produce neuronal necrosis in our studies. Thus, it is clear that (1) marked elevations in plasma glutamate and aspartate must occur for neuronal necrosis, and (2) threshold levels required to produce neuronal necrosis vary greatly with species. The available data indicate little danger to the healthy primate and humans from ingestion of the dicarboxylic amino acids under anything resembling a reasonable intake. However, there is no doubt that these amino acids are toxic to the neonatal mouse at high dose levels.