Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crystalline glutaminase-asparaginase which is effective against solid as well as ascites tumors was prepared from soil isolate organism Pseudomonas 7A. This enzyme has a ration of Vmax for L-glutamine and L-asparagine of 2.0. The presence of glutamic acid in the growth medium is essential for optimal enzyme production and glucose inhibits the production of glutaminase-asparaginase. The purification procedure provides an overall yield of 40 to 45% from crude cell extract to homogeneous glutaminase-asparaginase and is adaptable to large scale production of the enzyme. The specific activity of homogeneous enzyme is 160 +/- 15 i.u./mg of protein and the E1% 280 is 9.8. No disulfide or sulfhydryl groups appear to be present on the enzyme. The isoelectric point of glutaminase-asparaginase by isoelectric focusing on ampholine polyacrylamide gel plates is 5.8. The Km values for L-glutamine and L-asparagine are 4.6 and 4.4 X 10(-6) M, respectively. The enzyme catalyzes the hydrolysis of the D isomers of glutamine and asparagine at 87 and 69% the rate of the respective L isomers. L-Glutamic acid gamma-monohydroxamate is hydrolyzed at approximately the same rate as L-glutamine. The enzyme is not inhibited by ethylenediaminetetraacetate (0.1 mM), L-glutamate (30 mM), or L-aspartate (30 mM). Ammonium sulfate (10 mM) inhibits the enzymatic activity. The plasma half-life of Pseudomonas 7A glutaminase-asparaginase if 13 hours in normal mice and 43 hours in mice infected with the lactate dehydrogenase-elevating virus.
...
PMID:Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7Z. 0 41

A Chlamydomonas species isolated from a marine environment possesses an L-asparaginase, an enzyme not yet reported in the microalgae. This enzyme enabled the organism to grow as well with asparagine as sole nitrogen source as with inorganic nitrogen sources (NO3-, NH4+). Only the amide nitrogen was used for growth since growth did not occur on aspartate and aspartate accumulated in the media when cells were either grown on asparagine or during short-term incubations with L-[U-14C]asparagine. Cells grown on NO3-, NH4+, or L-asparagine in batch culture possessed equivalent asparaginase activities. However, nitrogen-limited cells possessed four times the activity of cells grown with sufficient nitrogen for normal growth, regardless of the possessed the lowest activity per cell, while lag phase and stationary phase cells possessed greater activity. The enzyme behaved like a periplasmic space enzyme since (1) breaking the cells did not release into solution more activity than was shown by whole cells and (2) whole cells converted L-[U-14C]asparagine to [14C]aspartate with little intracellular accumulation of radioactivity. Cell-free preparations of the enzyme possessed a Km value for asparagine of 1.1 x 10-4 M, with no glutaminase activity.
...
PMID:Asparagine metabolism and asparaginase activity in a euryhaline Chlamydomonas species. 4 71

The formation of the high-affinity (Km equal to 0.2 muM) L-glutamine transport system of Escherichia coli strain 7 (Lin) appears to be subject to the same major control as the glutamine synthetase (EC 6.3.1.2) of this gram-negative organism. Culture of cells under nitrogen-limited conditions provides maximum derepression of both the glutamine synthetase and the glutamine transport system. Nutritional conditions providing a rich supply of ammonium salts or available sources of nitrogen, i.e., conditions which repress the formation of glutamine synthetase, provide three- and 20-fold repression, respectively, of the glutamine transport system. Culture of cells with glutamine supplements of 2 mM does not increase the repression of high-affinity glutamine transport system beyond the level observed in the absence of glutamine. A second kinetically distinct low-affinity component of glutamine. A second kinetically distinct low-affinity component of glutamine uptake is observed in cells cultured with a glutamine-depleted nutrient broth. This second component is associated with the appearance of glutaminase A (EC 3.5.1.2) and asparaginase I (EC 3.5.1.1), a periplasmic enzyme. Parallel changes were observed in the levels of the high-affinity glutamine transport system and the glutamine synthetase when cells were cultured with the carbon sources: glucose, glycerol, or succinate.
...
PMID:Regulation of Glutamine Transport in Escherichia coli. 23 38

Nutrients as therapy for patients with cancer are important as adjunctive therapy, i.e., adequate nutrition may be important for the success of whatever form of therapy is administered. Diets deficient in certain amino acids have some selectivity when tested against experimental tumors propagated in vivo. Such diets have had limited clinical trial and have been characterized by poor patient acceptance. Enzymes that produce deficiencies of certain amino acids, e.g., asparaginase, glutaminase, methioninase appear to offer a more reasonable approach to development of selective amino acid deficiencies in man. Trace metals in excessive amounts may be toxic or carcinogenic to the host. Two heavy metal salts, Cis-diamine dichloroplatinum and gallium nitrate, have recently been shown to have anti-neoplastic effects in man. There is no conclusive evidence that vitamins, administered in large doses, have significant antineoplastic effects although large doses of vitamin A, vitamin C, and vitamin B12 have been used for this purpose. In contrast, certain vitamin analogs such as folate antimetabolites can cause tumor regression and are useful clinical treatment. An enzyme, carboxypeptidase G1, by splitting naturally occurring folates, may also have promise as a method of producing enzymic folate deficiency.
...
PMID:Nutrients, vitamins and minerals as therapy. 37 10

Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor.
...
PMID:L-Asparagainases from Citrobacter freundii. 40 50

Deamidase AG (asparaginase-glutaminase) from Pseudomonas fluorescens AG was shown to hydrolyze 1-glutamine and 1-asparagine highly effectively. Besides, the enzyme exhibited the rather high rate of deamidation of D-asparagine and D-glutamine (70% and 100%, respectively), Nalpha-butyl asparagine (63%) and among peptides -- of glycyl-L-asparagine (40%). L-glutamic acid gamma-methyl ester was hydrolyzed only slightly (5%). Effect of several substrate analogues on the deamidase AG activity was studied as well. Albiciine (alpha-amino-beta-ureide propionic acid) proved to be the strongest inhibitor (100%). Beta-Methyl aspartic acid, S-carbamoyl cysteine, alpha-ketoglutaric acid showed the slight inhibitory effect (20%). Amount of active centres per enzyme molecule was estimated by means of 14C-albiciine. Deamidase AG had apparently only one active centre. In estimation of relationship between the rate of reaction and substrate (L-asparagine) concentration, the reaction was found to follow Michaelis-Menten kinetics, K(m) = 4.5 with 10-4 M.
...
PMID:[Substrate specificity, inhibitors and kinetics of deamidase AG (asparaginase-glutaminase) from Pseudomonas fluorescens AG]. 41 63

Specific L-asparaginase activity and non-specific cytotoxicity of asparaginase-glutaminase preparation from Pseudomonas fluorescens were studied. Two cell lines, i.e. the asparaginase-dependent (Berkitt lymphoma cells) and the asparaginase-independent (the ovary cancer cells) were used as the test-system. Incorporation of 3H-timidine into DNA was used as the criterion of the drug effect on the cells. Krasnitin was used as the reference preparation. The preparation of asparaginase-glutaminase was inferior to krasnitine by its specific antitumour asparaginase activity and superior to it by the general cytotoxicity in the cells of CaOv. With the help of the above test-system it is possible to study the specific asparaginase activity of the drugs containing L-asparaginase. For studying the specific glutaminase properties it is necessary to develop another cell test-system.
...
PMID:[Biological properties of an asparaginase-glutaminase preparation from Pseudomonas fluorescens in cell cultures]. 41 58

Acinetobactor glutaminase-asparaginase was treated with [6-14C]diazo-5-oxonorleucine, reduced with sodium borohydride, and cleaved with cyanogen bromide. Radioactivity was present only in a 96-residue-N-terminal peptide which eluted as the second peptide peak on Sephadex G-50. Radioactivity was released with the threonine in position 12 during automatic sequencing of this peptide. The amino acid sequence of a 60-residue tn-terminal segment and a 16-residue C-terminal segment of this peptide was determined. Pseudomonas 7 A glutaminase-asparaginase was treated with [6-14C]diazo-5-oxonorleucine and reduced with sodium borohydride. Radioactivity was released with the threonine in residue 20 during automatic sequencing of the whole enzyme. Analysis of 26 N-terminal residues showed that an 8-residue segment containing the radioactive threonine was identical with that in Acinetobacter glutaminase-asparaginase and in Escherichia coli asparaginase. Additional identical residues were noted in the N-terminal regions of these enzymes.
...
PMID:Amino acid sequence of the diazooxonorleucine binding site of Acinetobacter and Pseudomonas 7A glutaminase--asparaginase enzymes. 61 99

Desialised orosomucoid (alpha-1-acidic glycoprotein) was coupled to Pseudomonas 7A glutaminase-asparaginase by glutaraldehyde, iodinated and injected into mice. The half-life of radioactivity and glutaminase activity in plasma was about 7 min. Radioactivity and glutaminase activity in the liver reached a peak at about 20 min. The radioactivity in liver then declined with a half-life of about 20 min. Enzyme activity in liver declined with a half-life of about 10 min. The ratio of enzyme activity to radioactivity was lower in the liver than in plasma at all times during the experiment, indicating rapid hepatic inactivation of the enzyme. Uptake into the liver could be blocked by excess desialised orosomucoid. Glutamine levels in the liver were about 10% of normal for 44 min but returned to 50% of normal by 93 min. Intestines, kidney and spleen failed to exhibit any appreciable uptake of desialated orosomucoid glutaminase-asparaginase.
...
PMID:Kinetics of uptake and activity in mouse liver of glutaminase coupled to desialated orosomucoid. 62 51

Growing cells of Yersinia pseudotuberculosis, but not those of closely related Yersinia pestis, rapidly destroyed exogenous L-aspartic and L-glutamic acids, thus prompting a comparative study of dicarboxylic amino acid catabolism. Rates of amino acid metabolism by resting cells of both species were determined at pH 5.5, 7.0, and 8.5. Regardless of pH, Y. pseudotuberculosis destroyed L-glutamic acid, L-glutamine, L-aspartic acid, and L-asparagine at rates greater than those observed for Y. pestis. Although rates of proline degardation were similar, its metabolism by Y. pestis at pH 8.5 resulted in excretion of glutamic and aspartic acids. Similarly, Y. pestis excreted aspartic acid when incubated with L-glutamic acid (pH 8.5) or L-asparagine (pH 5.5, 7.0, and 8.5). Aspartase activity was not detected in extracts of 10 strains of Y. pestis but was present in all 11 isolates of Y. pseudotuberculosis. The latter contained significantly more glutaminase, asparaginase, and L-glutamate-oxalacetate transminase activity than did extracts of Y. pestis; specific activities of L-glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase were similar. The observed differences in dicarboxylic amino acid metabolism are traceable to asparatase deficiency in Y. pestis and may account for the slow doubling time of this organism relative to Y. pseudotuberculosis.
...
PMID:Consequences of aspartase deficiency in Yersinia pestis. 71 77


1 2 3 4 5 6 7 8 9 10 Next >>

---