Antineoplastic Agents
Frank A. Barile in Barile’s Clinical Toxicology, 2019
The enzyme L-asparaginase produces tumor cell death through the activation of apoptosis. In particular, the drug deprives the cell of asparagine. This amino acid is crucial for protein synthesis because the enzyme catalyzes the hydrolysis of circulating asparagine to aspartic acid and ammonia. Consequently, L-asparaginase stops the progression of cells through the cell cycle. Its unique mechanism of action supports its inclusion with other antitumor drugs as part of a chemotherapeutic program, especially in the treatment of acute lymphoblastic leukemia and other lymphoid malignancies. The drug is conveniently administered I.V. or intramuscularly (I.M.) in a variety of regimens and schedules but poses a serious toxicity threat due to its bacterial origin—that is, antigenicity. Hypersensitivity and anaphylactic reactions occur in 5 to 20% of patients, most notably when administered intermittently. Other toxicities related to its mechanism of action include hyperglycemia, coagulopathies, immunosuppression, and hemorrhage, all of which are potentially fatal.
Micronutrient Supplementation and Ergogenesis — Metabolic Intermediates
Luke Bucci in Nutrients as Ergogenic Aids for Sports and Exercise, 2020
The dispensable dicarboxylic amino acid, aspartic acid, is also a metabolic intermediate in several biochemical pathways such as the tricarboxylic acid and urea cycles.460 Amino acid salts were hypothesized as mineral transporters to subcellular sites, aiding in metabolism by replenishment of electrolytes.461 For these reasons, monopotassium and monomagnesium DL-aspartate in equal amounts were studied by Laborit and co-workers.462–464 They deduced that metabolic effects from the aspartate moiety contributed to decreased oxygen consumption. Meanwhile, Nieper indicated that intracellular transport of potassium and magnesium by aspartate salts corrected deficiencies and reduced hypoxia in human ischemic hearts.461
Pyruvate carboxylase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The complex biochemical picture reminiscent of a defect in the urea cycle appears to result from depletion of intracellular oxaloacetate and aspartate [22, 23, 27]. Aspartate is a source of the second nitrogen of urea (Figure 48.1); its deficiency would lead to citrullinemia and hyperammonemia. Aspartate is also involved in the shuttle of reducing equivalents from cytosol to mitochondria [46] by which the NAD+/NADH ratio (nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) is very oxidized in the cytosol and reduced in mitochondria; its lack would make the cytosol more reduced and the mitochondria more oxidized, as occurs in this phenotype.
Restoring the biological activity of crizanlizumab at physiological conditions through a pH-dependent aspartic acid isomerization reaction
Published in mAbs, 2023
Fabian Bickel, François Griaud, Wolfram Kern, Frieder Kroener, Manuela Gritsch, Jérôme Dayer, Samuel Barteau, Blandine Denefeld, Chi-Ya Kao-Scharf, Manuel Lang, Izabela Slupska-Muanza, Carla Schmidt, Matthias Berg, Jürgen Sigg, Lina Boado, Dirk Chelius
At pH 6.0, basic variants (mainly the BP3 variant) and acidic variants increased, showing that succinimide is formed, which partly hydrolyzes to iso-aspartic acid (AP1 and AP2) and aspartic acid (main). Since the main peak decreases and the acidic peaks 1 and 2 increase, the formation of iso-aspartic acid is finally predominant. This is based on the succinimide hydrolysis to iso-aspartic acid and aspartic acid with a ratio of 3:1.4,12,13 Accumulation of succinimide is known to be accelerated under those mildly acidic conditions8 combined with increased temperatures.11 Independent of the tested pH, the formation of succinimide is not unlimited: although the cyclization reaction is favored at pH conditions below pH 6.3, succinimide also hydrolyzes at those conditions, reflected by an increase of iso-aspartic acid (acidic variants). Even at pH 5.0 the basic variants decrease again after reaching a maximum (data not shown). The equilibrium between the succinimide formation and its hydrolysis is pH dependent, so the maxima that basic variants can reach differ. The lower the pH, the more the equilibrium favors succinimide formation. Higher succinimide maxima are present at lower pH values compared to neutral pH conditions. This behavior is also in agreement with reported rate constants for the succinimide formation, which increase by lowering the pH from 6 to 4. It has been reported that rate constants of the succinimide hydrolysis were increased by raising pH conditions from 6 to 8.5.11
The low glutamate diet improves cognitive functioning in veterans with Gulf War Illness and resting-state EEG potentially predicts response
Published in Nutritional Neuroscience, 2022
Anna E. Kirkland, Michael Baron, John W. VanMeter, James N. Baraniuk, Kathleen F. Holton
The low glutamate diet is a healthy, whole food diet which restricts the intake of excitotoxins, which are amino acids in the diet that can over-excite glutamate receptors (e.g. free forms of glutamate and aspartate). Free forms of glutamate, such as monosodium glutamate (MSG), can be used as food additives to enhance the flavor of food [13]. Free glutamate can also be found in natural sources, like soy sauce, aged cheeses, seaweed, and tomato sauce. Aspartate is also restricted as it is an analog of glutamate. It is found most often in the diet as aspartame (a dipeptide of aspartate and phenylalanine), which is a commonly used artificial sweetener; and aspartate can also be found in hydrolyzed proteins and in gelatin. The low glutamate diet emphasizes consumption of foods which are protective against excitotoxicity and oxidative stress. More details on the low glutamate diet can be found elsewhere [12].
Recent developments in Phos-tag electrophoresis for the analysis of phosphoproteins in proteomics
Published in Expert Review of Proteomics, 2022
There are no reports on the relationship between the number of glutamates and the changes in mobility observed in Phos-tag SDS-PAGE or between the sequence localization of glutamate and the changes in mobility. Glutamate-containing proteins sometimes show a decrease in mobility like phosphorylated proteins do in Phos-tag SDS-PAGE. Aspartate is also an acidic amino acid similar to glutamate and used to mimic phosphorylation in studies on protein phosphorylation. However, there is also no report that the mobility of aspartate-rich proteins was reduced in Phos-tag SDS-PAGE. Furthermore, no study has reported why aspartate does not affect mobility. Therefore, it might be necessary to perform analyses such as phosphoprotein shotgun analysis, phosphoprotein detection using ProQ diamond, or Western blotting using an antibody specific to the phosphorylation sites to confirm whether the change in mobility observed in Phos-tag SDS-PAGE is due to protein phosphorylation or glutamate. In the future, the development of a novel method will be required to easily distinguish between glutamate-containing and phosphorylated proteins.
Related Knowledge Centers
- De Novo Synthesis
- Essential Amino Acid
- Genetic Code
- Neuromodulation
- Peptide
- Protein
- Amino Acid
- Neurotransmitter
- Proteinogenic Amino Acid
- Asx Turn