Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A positive selection method, D-aspartic acid beta-hydroxamate resistance, was used to isolate Saccharomyces cerevisiae strains lacking the ability to synthesize asparaginase II. Of 100 such mutant strains, 93 exhibited mutations which were allelic with asp3, a previously characterized mutation. The other seven strains carried a new mutation, asp6. The asp6 mutation segregated 2:2 in asp6 X wild-type crosses and assorted from the asp3 mutation in asp6 X asp3 crosses. All seven asp6 mutant isolates reverted at a relatively high frequency, whereas the asp3 mutant isolates did not revert under the same conditions. Various independent asp3 isolates were mated to give heteroallelic diploids, which when sporulated and spread on D-asparagine medium yielded no recombinant strains.
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PMID:Asparaginase II of Saccharomyces cerevisiae: positive selection of two mutations that prevent enzyme synthesis. 636 97

Crude extracts of Thermoactinomyces vulgaris 13 M.E.S. were prepared by different procedures and their L-asparaginase activity was compared. The optimum conditions for the enzyme activity in the crude extract was exerted at pH 8.8, using borate or tris-HCl buffer, or at pH 7.4, using phosphate buffer, after a reaction time of 30 minutes at 50-55 degrees C, using 1.35-5.4 mg protein of the crude extract. The enzyme showed an apparent km value of 4.5 x 10(-3), was more thermostable in crude extracts than in whole cells, and was inhibited by HgCl2, KCN, DL-asparagine, L-aspartic acid, and ammonium hydroxide. Enzyme purification by alcohol precipitation and gel filtration was attempted.
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PMID:L-asparaginase activity in cell-free extracts of Thermoactinomyces vulgaris 13 M.E.S. 664 56

L-asparaginase was immobilized under aseptic conditions in spherical microparticles of polyacrylamide. To avoid direct contact between blood and enzyme, we have applied the immobilized L-asparaginase in microparticles on the outer surface of the capillary fibers of a hemofilter. The hemofilters were very efficient in the transformation of L-asparagine to L-aspartic acid, both in vitro and in vivo. L-Asparagine in buffer (50 microM in 5 liters) was converted to L-aspartic acid within 60 min after circulation through a hemofilter containing 2000 I.U. of L-asparaginase. Circulating L-asparagine in healthy sheep (about 40-50 microM was reduced to low levels after 2 to 3 hr of perfusion with a unit containing 2000 I.U. of L-asparaginase. The reduction persisted for 3 to 4 hr after terminated treatment. Repeated, extracorporeal treatments in sheep showed that the L-asparagine decrease induced an increased resynthesis of L-asparagine, probably due to the action of the L-asparagine synthetase.
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PMID:Use of immobilized L-asparaginase in acrylic microparticles in an extracorporeal hollow-fiber dialyzer. 683 69

Kinetic parameters, substrate specificity and exclusivity of ligands at binding sites of L-glutaminase-L-asparaginase purified from Acinetobacter glutaminasificans were studied in order to gain knowledge about the dual activities of this enzyme and its inhibition by structural analogs. Both L-glutamine and L-asparagine, which showed similar Km (4 approximately 7 X 10(-5) M) and Vmax (molecular activity 1.0 min-1) values, were competitive with each other for the substrate binding site. The products, L-glutamic acid and L-aspartic acid, showed competitive inhibition with respect to either L-glutamine or L-asparagine as substrates. Multiple inhibition of the glutaminase activity by L-glutamic acid and L-aspartic acid indicated that these ligands are mutually exclusive at the product-releasing site. The initial rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in decreasing order of activity): 6-diazo-5-oxo-L-norleucine (DON), L-methionine sulfoximine, azaserine, and Acivicin. DON and azaserine inhibited both the asparaginase and glutaminase activities in a time-dependent and irreversible manner. The kinetic data suggest an ordered mechanism with glutamine or asparagine as the first substrate and glutamic acid or aspartic acid, respectively, as the last product. These results also suggest that a single mechanism and a single set of binding sites are responsible for catalyzing both of the enzyme's activities. The data also showed that succinylated enzyme, which has a 10-fold increase of plasma half-life in animals and humans and, thus, has benefit as a cancer chemotherapeutic agent, retained its catalytic activity and maintained Km and Vmax values similar to the native enzyme.
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PMID:Kinetic properties and inhibition of Acinetobacter glutaminase-asparaginase. 683 61

The effect of L-aspartic acid, L-asparagine and/or L-asparaginase were compared with those of imipramine on immobility, number of defecations, increase of nociceptive threshold, and hypothermia, induced by forced swimming in rats. L-Aspartic acid was found to be as effective as imipramine in reducing the effects of forced swimming, presumable by normalizing the decreased level of endogenous L-aspartic acid, due to the inhibition of L-asparaginase activity and/or by stimulating the inhibited enzyme. The other treatments antagonized the immobility, but not the increased number of defecations. All compounds abolished the elevation of nociceptive threshold and hypothermia.
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PMID:Effects of L-aspartic acid, L-asparagine and/or L-asparaginase on forced swimming-induced immobility, analgesia, and decrease in rectal temperature in rats. 705 52

Seventy-five rats, divided into five groups, were given D-aspartic acid (D-Asp), L-Asp and D + L-Asp in ratio 1/1 or 1/2 for one week. The body weight, food and fluid intakes, and rectal temperature of the rats received D-Asp or D + L-Asp in 1/1 ratio significantly decreased. The decrease in rectal temperature was antagonized by naloxone. L-Asp given together with D-Asp in 1/2 ratio prevented D-Asp-caused decrease in body weight, food and fluid intakes, and rectal temperature. Although D-amino acids, as antipeptidases have some effects through endorphinergic systems, D-Asp (an inhibitor of L-asparaginase) seems to act at the level of L-asparaginase presumably by increasing the level of endorphins since L-Asp antagonizes the inhibitory effect of both D-Asp and morphine.
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PMID:Antagonistic effect of L-aspartic acid on decrease in body weight, and food and fluid intake, and naloxone reversible rectal temperature depression caused by D-aspartic acid. 718 48

The effects of D- and L-aspartic acids on the nociceptive tail flick reflex in mice were investigated. D-Aspartic acid (115-230 mg/kg, IP) was found to increase tail flick latency significantly. Naloxone (0.1 mg/kg) abolished the analgesic effect of D-aspartic acid (115 mg/kg). Morphine and D-aspartic acid, when combined at their nonanalgesic doses, led to significant analgesia. It may be concluded that the opioid system is involved in the antinociceptive effect of D-aspartic acid. Both morphine and D-aspartic acid were previously reported to inhibit L-aspartic acid production via blockade of L-asparaginase. L-Aspartic acid, which was ineffective alone, significantly inhibited the antinociceptive effects of both D-aspartic acid and morphine.
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PMID:Antinociceptive effect of D-aspartic acid in mice. 767 49

The investigation on the localization of L-asparaginase, the enzyme involved in the synthesis of L-aspartic acid, has been carried out using the immunohistochemical method. Antibodies against this enzyme were obtained immunizing BALB/c mice with purified Escherichia coli L-asparaginase. Light microscopic observation revealed positive immunoreactivity in the great majority of neurons and glial cells, and electron microscopic analysis demonstrated immunological localization of the enzyme in the cytosol. The ubiquitous distribution of L-asparaginase suggests its involvement in many important functions of the central nervous system.
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PMID:Light and electron microscopic immunolocalization of L-asparaginase in the rat central nervous system. 800 45

The crystal structure of L-asparaginase from Erwinia chrysanthemi in the presence and absence of L-aspartate was determined at 1.8 A resolution. Conserved residues in a left-handed crossover (a rare occurrence in protein structures) link pairs of dimers into the catalytically active tetrameric form of the enzyme. The structure of ErA containing bound aspartic acid shows that this unusual strand connectivity is an essential part of the active site architecture, responsible for releasing the product of the enzymatic hydrolysis. The orientation of the bound aspartate indicates for the first time a threonine residue as a catalytic nucleophile.
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PMID:A left-handed crossover involved in amidohydrolase catalysis. Crystal structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate. 834 75

L-asparaginase and L-aspartate aminotransferase are both involved in the synthesis of L-aspartic acid. It has been observed that L-asparaginase is involved in the immunosuppressor morphine-dependent syndrome in lymphoid cells whereas L-aspartic acid blocks the development of this syndrome. The aim of the present study was to clarify the localization of L-AATase activity and L-asparaginase in rat lymph nodes using histoenzymological and immunohistochemical methods, respectively. No positive reaction was demonstrated for L-AATase while L-asparaginase shown to be present in lymphocytes and lymphoblastic cells. These observations lead us to suggest that L-asparaginase is the enzyme mainly responsible for the synthesis of the L-aspartic acid necessary for satisfying the living requirements of lymphoid cells. Therapeutically administered L-asparaginase could exert its action intracellularly after crossing the cell membrane.
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PMID:L-aspartate aminotransferase and L-asparaginase in rat lymph node: a histoenzymological and immunohistochemical study. 863 Apr 37


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