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)

L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect.
Cancer Res 1976 Sep
PMID:L-Asparagine synthetase in serum as a marker for neoplasia. 1 81

Complement fixation has been shown to occur when asparaginase reacts with specific antibody. This is as a result of an antigenic determinant common to the four bacterial asparaginases. Patients on asparaginase therapy may produce antibodies and these could be demonstrated by complement fixation.
N Z Med J 1977 Sep 28
PMID:Antibodies to bacterial L-asparaginases. 7 27

The uptake of L-asparagine by Escherichia coli K-12 is characterized by two kinetic components with apparent Km values of 3.5 muM and 80 muM. The 3.5 muM Km system displays a maximum velocity of 1.1 nmol/min per mg of protein, which is a low value when compared with derepressed levels of other amino acid transport systems but is relatively specific for L-asparagine. Compounds providing effective competition for L-asparagine uptake were 4-carbon analogues of the L-isomer with alterations at the beta-amide position, i.e., 5-diazo-4-oxo-L-norvaline (Ki = 4.6 muM), beta-hydroxyamyl-L-aspartic acid (Ki = 10 muM), and L-aspartic acid (Ki = 50 muM). Asparagine uptake is energy dependent and is inhibited by a number of metabolic inhibitors. In a derived strain of E. coli deficient in cytoplasmic asparaginase activity asparagine can be accumulated several-fold above the apparent biosynthetic pool of the amino acid and 100-fold above the external medium. The high affinity system is repressed by culture of cells with L-asparagine supplements in excess of 1 mM and is suggested to be necessary for growth of E. coli asparagine auxotrophs with lower supplement concentrations.
J Bacteriol 1975 Sep
PMID:L-asparagine uptake in Escherichia coli. 23 25

The N-[p-(fluorosulfonyl)benzyl] derivatives of L-asparagine and L-glutamine (1a,b) were synthesized as potential inhibitors of L-asparagine synthetase (ASase). Condensation of p-(fluorosulfonyl)benzylamine (2) with the suitably protected amino acid in the presence of dicyclohexylcarbodiimide, followed by deblocking, afforded 1a and 1b. Derivatives 1a and 1b at 10 mM inhibit ASase isolated from Novikoff hepatoma (rats) by 60 and 46%, respectively. Preliminary results on inhibition of Jensen sarcoma (L-asparaginase sensitive) and JA-1 sarcoma (L-asparaginase resistant) tissue cultures by 0.3 mM 1a (139,90%) and 1b (101, 103%), respectively, are discussed.
J Med Chem 1975 Sep
PMID:Potential inhibitors of L-asparagine biosynthesis. 3. Aromatic sulfonyl fluoride analogs of L-asparagine and L-glutamine. 24 24

L-asparaginase therapy is often limited by allergy or toxicity and probably in some cases by antibody mediated inactivation of the enzyme. These problems can be avoided by extracorporeal application of l-asparaginase. As the enzyme is a stable tetramer with high molecular weight it cannot pass through the dialysis membrane in contrast to the amino acid l-asparagin which is destroyed. The resulting l-asparagin depletion of the plasma is sufficient for therapeutic success. Effective extracorporeal l-asparaginase therapy is demonstrated in two patients with ALL who were resistant to other chemotherapy and could not be treated intravenously because of allergy and toxicity.
Blut 1977 Sep 29
PMID:[Extracorporeal treatment with L-asparaginase (author's transl)]. 26 43

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.
Br Med J 1978 Sep 16
PMID:Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate. 27 87

The asparaginase activity of the Montreal strain of BCG and of 2 of its phenotypes varies with the age of the culture; it starts to increase at the midlog phase of growth, reaches a maximum value near the end of this phase and decreases during the stationary or autolytic phase. However, the variations in this enzyme activity are greater in 2 the phenotypes than in the parental BCG.
Ann Microbiol (Paris) 1975 Sep
PMID:Asparaginase activity of BCG and its phenotypes in relation to culture phases. 76 91

Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.
Med Clin North Am 1976 Sep
PMID:The definitive treatment of children with acute leukemia. 78 18

L-Asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) from Escherichia coli B was modified by treatment with 2,4,6-trinitrobenzene-1-sulfonic acid at pH 7.5. The introduction of 13 trinitrophenyl groups into one mol of the tetrameric enzyme (TNP 13-asparaginase) results in a loss of 67% of the catalytic activity while the presence of 20 groups (TNP 20-asparaginase) reduces the enzymatic activity by 88%. The modified proteins are homogeneous as judged by disc gel electrophoresis and by the monodisperse boundary in the analytical ultracentrifuge having a sedimentation coefficient of 7.2 S. The rate of dissociation of the TNP 13-asparaginase is twice as fast and TNP 20-asparaginase three times as fast as that of unmodified asparaginase in 4 M urea. Trinitrophenylated subunits in 8 M urea can reassociate into the tetramer after removal of urea by dialysis or by dilution. hybridization of unmodified and TNP subunits indicates that that trinitrophenyl derivatives qualify as suitable variants for studying subunit interactions in oligomeric proteins.
Biochim Biophys Acta 1976 Sep 14
PMID:The effect of trinitrophenylation on subunit interactions in L-asparaginase. 78 47

Glutaminase-asparaginase from Pseudomonas 7A appears to have four subunits with a molecular weight of 36,000 +/- 500 by sedimentation equilibrium in 5.9 M guanidine HCl and 34,000 by amino acid analysis. Analytic sedimentation equilibrium of the native enzyme showed a molecular weight of 140,000 +/- 3,300 with no signs of association or dissociation. Moving boundary and zone sedimentation in buffer showed normal behavior with sedimentation coefficients of 7.92 and 7.75 S, respectively. In contrast, the enzyme appeared to polymerize during zone sedimentation when the initial protein concentration was greater than 1 mg/ml and the buffer contained asparagine, glutamine, or 5-diazo-4-oxonorvaline. An extension of our method for active enzyme sedimentation is described which utilizes the changes in absorption during hydrolysis of asparagine by low concentrations of enzyme. Polymerization was not seen under these conditions.
J Biol Chem 1976 Sep 10
PMID:Physical properties of antitumor glutaminase-asparaginase from Pseudomonas 7A. 95 89


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