Aspartate inhibition

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

A number of studies have shown that natural metabolites can inhibit transamination. With a partially purified mung bean preparation which could use lysine, methionine, or aromatic amino acids as amino donors, it was found that the aliphatic substrates (e.g., lysine and methionine) inhibited the transamination of phenylalanine. The extent of this inhibition was related to their effectiveness as substrates, suggesting that they competed with phenylalanine (Gamborg, 1965). Using the highly purified but multispecific aromatic amino acid (and aspartate) aminotransferase from bush bean. Forest and Wightman (1973) demonstrated that 40 mM aspartate inhibited transamination of L-phenylalanine (40 mM) by 85%. Further experiments showed that elevated concentrations of phenylalanine reduced the inhibition by aspartate double-reciprocal plots indicated competitive inhibition. These... 

Candidate protease inhibitor drugs must be relatively specific for the HIV-1 protease. Many other aspartic proteases exist in the human body and are essential to a variety of body functions, including digestion of food and processing of hormones. An ideal drug thus must strongly inhibit the HIV-1 protease, must be delivered effectively to the lymphocytes where the protease must be blocked, and should not adversely affect the activities of the essential human aspartic proteases. 

PEP carboxylase occurs in yeast, bacteria, and higher plants, but not in animals. The enzyme is specifically inhibited by aspartate, which is produced by transamination of oxaloacetate. Thus, organisms utilizing this enzyme control aspartate production by regulation of PEP carboxylase. Malic enzyme is found in the cytosol or mitochondria of many animal and plant ceils and is an NADPIT-dependent enzyme. 

A possible explanation for the superiority of the amino donor, L-aspartic add, has come from studies carried out on mutants of E. coli, in which only one of the three transaminases that are found in E. coli are present. It is believed that a branched chain transaminase, an aromatic amino add transaminase and an aspartate phenylalanine aspartase can be present in E. coli. The reaction of each of these mutants with different amino donors gave results which indicated that branched chain transminase and aromatic amino add transminase containing mutants were not able to proceed to high levels of conversion of phenylpyruvic add to L-phenylalanine. However, aspartate phenylalanine transaminase containing mutants were able to yield 98% conversion on 100 mmol l 1 phenylpyruvic acid. The explanation for this is probably that both branched chain transaminase and aromatic amino acid transminase are feedback inhibited by L-phenylalanine, whereas aspartate phenylalanine transaminase is not inhibited by L-phenylalanine. In addition, since oxaloacetate, which is produced when aspartic add is used as the amino donor, is readily converted to pyruvic add, no feedback inhibition involving oxaloacetate occurs. The reason for low conversion yield of some E. coli strains might be that these E. cdi strains are defident in the aspartate phenylalanine transaminase. 

The best results were obtained with L-aspartic add as the amino donor for P. denitrificam and phenylpyruvic add as the amino acceptor. With L-aspartic add, conversion of phenylpyruvic add exceeded 90%. This may be attributed to absence of feedback inhibition of the reaction due to metabolism of file reaction product, oxaloacetic add. When using glutamic acid the conversion of phenylpyruvic add did not exceed 60%. 

The type of intermediate that is formed in the slow inhibition with D-gly-cals was identified, with the aid of the ) -D-glucosidase A3 from Asp. wentii, as an ester of 2-deoxy-D-araA/ o-hexose with an aspartic acid side-chain. The same aspartoyl residue had already been shown, by labeling with con-duritol B epoxide (see Section 111,1), to be essential for -D-glucoside hydrolysis. In addition, this aspartate was found to form a glycosyl -enzyme... 

Aspartate transcarbamoylase (ATCase), the catalyst for the first reaction unique to pyrimidine biosynthesis (Figure 34-7), is feedback-inhibited by cytidine tri-... 

Since biosynthesis of IMP consumes glycine, glutamine, tetrahydrofolate derivatives, aspartate, and ATP, it is advantageous to regulate purine biosynthesis. The major determinant of the rate of de novo purine nucleotide biosynthesis is the concentration of PRPP, whose pool size depends on its rates of synthesis, utilization, and degradation. The rate of PRPP synthesis depends on the availabihty of ribose 5-phosphate and on the activity of PRPP synthase, an enzyme sensitive to feedback inhibition by AMP, ADP, GMP, and GDP. 

In other experiments, we found that PCP also inhibited ACh release induced by the amino acid transmitter candidates, L-glutamate and L-aspartate. Release of ACh by these amino acids had a similar Mg++sensitivity to that induced by NMDA, suggesting an action of these amino acids on the N-type receptor. No inhibition of release by PCP could be seen in the presence of Mg++. 

L-Asparaginase is an enzyme that may be produced by Escherichia coli. Asparaginase hydrolyzes the reaction of asparagines to aspartic acid and ammonia to deplete lymphoid cells of asparagine, which inhibits protein synthesis. The... 

The inhibition of C a2+-ATPase at the active site by ATP-Im or ADP-Im with the participation of Ca2+ is illustrated by the following model. In the reaction of ATP-imidazolide with the carboxylate of Asp 351, a mixed anhydride is formed with the aspartate residue, followed by presumably nucleophilic attack of a lysine side chain, thereby displacing the nucleotide and leading to an intramolecular crosslink.[1]... 

Ida I., Aami T., Kuribara H. Inhibition of cocaine sensitization by MK-801 a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist evaluation by ambulatory activity in mice. Jpn. J. Pharmacol. 69 83, 1995. 

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