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

Two distinct L-asparaginase (EC 3.5.1.1) activities were detected in guinea pig liver: Asparaginase 1 and Asparaginase 2. Asparaginase 1 has been purified 272 fold from the crude homogenate; its molecular weight was evaluated by gel filtration to be about 150 000. The purified preparation was shown to be homogeneous by cellulose acetate strip and polyacrylamide disc-gel electrophoresis. Asparaginase 2 has been purified 63.5 fold from the crude homogenate. Its molecular weight was evaluated by gel filtration to be about 21 500. Cellulose acetate strip electrophoresis demonstrated two bands, one of which corresponded to Asparaginase 1 and the other to Asparaginase 2. Cellular fractionation in the ultracentrifuge, showed Asparaginase 1 to be present only in the cytosol fraction. Asparaginase 2 which was unstable at 105 000 X g seemed mostly localized in the mitochondria and secondarily in the cytoplasmic fraction.
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PMID:Guine pig liver L-asparaginase. Separation, purification, and intracellular localisation of two distinct enzymatic activities. 123

One of the main criteria in the differentiation between acute lymphoblastic (ALL) and acute myeloblastic leukemias (AML) is the presence of granules in the blasts of the latter. Recently, several groups have described a form of ALL with prominent intracytoplasmatic granules (G-ALL) in the blasts. The granules in the G-ALL blasts do not contain myeloperoxidase, but sometimes have lipids that stain with Sudan black B (SBB). We describe a case of G-ALL in a five-year-old girl whose peripheral blood and bone marrow was compound of 98% lymphoblasts, 30% of which, had prominent azurophilic intracytoplasmatic granules. The granules did not have peroxidase, acid phosphatase, varies; is directly proportional to naphthyl acetate esterase. However 5% of the blasts had sudanophilic granules and 60% were positive for the periodic acid-Schiff reaction. The blasts expressed the CD10 (CALLA) and Dr antigens, and were negative for surface immunoglobulins or the CD4, CD8, or CD14, antigens. Only 18% of cells formed rosettes with sheep erythrocytes. The patient responded to vincristine, prednisone and L-asparaginase. Based on the finding we diagnosed this as a CALLA positive G-ALL. By conventional criteria this case would have been wrongly classified as AML.
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PMID:[Granular CALLA-positive acute lymphoblastic leukemia]. 210 43

A membrane-bound L-asparaginase (EC 3.5.1.1) of Tetrahymena pyriformis was purified to homogeneity. The purified enzyme is a lipoprotein, since it is inactivated by phospholipase C and its activity is restored by the addition of naturally occurring lipids, such as phosphatidylcholine, triolein and oleyl acetate. The relative effectiveness of a variety of phospholipids, free saturated and unsaturated fatty acids, or neutral lipids, such as esters of fatty acids and glycerides, with respect to the activation of purified L-asparaginase is compared. Enzyme activity is reconstituted in the presence of lipids and evidence for the formation of an enzyme-phospholipid complex is presented. The data of this report suggest that L-asparaginase may have a requirement for lipids that reconstitute a physiological hydrophobic environment, similar to the one existing in vivo.
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PMID:In vitro alterations of L-asparaginase activity of Tetrahymena pyriformis by lipids. 314 10

Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but showed acid phosphatase (ACP) and alpha-naphthyl acetate esterase (ANAE) activity inhibitable by sodium fluoride. They were identified as megakaryoblasts by the platelet peroxidase reaction. Cytogenetic studies showed multiple chromosomal abnormalities in both cases. Chemotherapy with vincristine, prednisone, and L-asparaginase was without effect, while daunorubicin and cytosine arabinoside induced a complete remission in one case. The second case responded to a combination of cytosine arabinoside, daunorubicin, and 6-thioguanine. This article documents that acute megakaryoblastic leukemia occurs in early childhood and describes its clinical, pathologic, and cytogenetic features. Previous reports of childhood "myelofibrosis" are reviewed, and their possible relationship with acute megakaryoblastic leukemia is discussed.
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PMID:Acute megakaryoblastic leukemia in early childhood. 686 Jul 97

The influence of cytostatic drugs (L-asparaginase, vincristine, 6-mercaptopurine, amethopterine, prednisone) on the activity of alkaline and acid phosphatase, alpha-naphtol-acetate esterase, the content of glycogen and lipids in leukocytes of peripheral blood in patients with acute leukemia was investigated. Under the influence of anti-leukemic drugs some cytochemical reactions typically changed in different forms of acute leukemia showed tendency to normalization being sometimes more distinctive than leukocytosis or even than white blood picture. In patients who did not show any improvement during the treatment the disturbances of cytochemical reactions intensified or, sometimes, remaining unchanged. The repetition of examination of cytochemical reactions changing distinctively in the chemotherapy may simplify the treatment control by better estimation of its efficiency and give some prognostic hints.
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PMID:Influence of chemotherapy on some cytochemical reactions in patients with acute leukemia. 693 14

The liver from the Wistar rat was incubated either in the solution of 1 micro Ci acetate-1-14C or 0.1 micro Ci mevalonic acid-2-14C, and incorporations of radioactivity to phospholipid and cholesterol were estimated respectively. The incorporation of labeled acetate to cholesterol in the L-asparaginase-treated rat was significantly lower than that in the controls. However, there were no differences of the incorporation into the mevalonic acid between the study group and the controls. These results suggest that the inhibitory mechanism may exist between the steps of acetate and mevalonic acid.
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PMID:The effect of L-asparaginase on cholesterol biosynthesis. 731 80

Few data exist about the incidence of drug-induced pancreatitis in the general population. 20 cases of drug-related pancreatitis were reported in Switzerland over a period of 12 years. The proportion of cases of pancreatitis caused by drugs is estimated to be around 2% in the general population, with much higher proportions in specific subpopulations, such as children and patients who are HIV positive. The literature about drug-induced pancreatitis consists mainly of anecdotal case reports. Clear evidence of a definite association with pancreatitis, by means of rechallenge tests, or consistent case reports, supported by animal experiments or data on the incidence of acute pancreatitis in drug trials exists for didanosine, valproic acid (sodium valproate), aminosalicylates, estrogen, calcium, anticholinesterases and sodium stibogluconate. An association with drug-induced pancreatitis is likely but not definitely proven for thiazide diuretics, pentamidine, ACE inhibitors, asparaginase, vinca alkaloids, some nonsteroidal anti-inflammatory drugs and clozapine. Pancreatitis is possibly caused by azathioprine, furosemide (frusemide), tetracycline, metronidazole, isoniazid, rifampicin (rifampin), sulphonamides, cyclosporin and some antineoplastic drugs. Many drugs have been reported to be associated with acute pancreatitis. However, lack of rechallenge evidence, consistent statistical data, or evidence from experimental studies on a possible mechanism prohibit definitive conclusions about most of them. The high incidence of concurrent illnesses known to induce acute pancreatitis, makes a trigger role or co-factor role for the drug seem most likely.
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PMID:Drug-induced pancreatitis. 882 18

Hexamita inflata is an amitochondriate flagellated protozoon which inhabits O(2)-limited environments. With the aid of 1H NMR spectroscopy, analysis of the metabolic fluxes in H. inflata grown in complex media under limited O(2) was performed. Almost complete carbon recovery from maltose (the principle carbohydrate source in the medium) catabolism was calculated from the measured increase in concentration of ethanol, alanine, acetate and lactate (and estimated CO(2) production). Difference spectra and amino acid analysis also identified changes in concentration of metabolites belonging to the arginine dihydrolase (ADH) pathway. The enzymes of the ADH pathway were detected in extracts with the following activities (in nmoles min(-1) x (mg of protein) x (-1)): arginine deiminase, 3.30; catabolic ornithine carbamyltransferase (OCT), 1.3; anabolic OCT, 93.0; and carbamate kinase, 1829. The organism metabolized the ornithine produced from catabolic OCT activity to putrescine via ornithine decarboxylase (ODC). The polyamines, spermidine and spermine, were formed by the sequential addition of the aminopropyl group of decarboxylated S-adenosyl-L-methionine (SAM) by the respective polyamine synthases. In addition, asparaginase activity was confirmed in H. inflata, catalysing the deamination of asparagine generating aspartate and ammonia. This study also indicates that, as with other amitochondriate protozoa and some bacteria, the ADH pathway significantly contributes to the energy yield of the cell, particularly under O(2)-limited conditions.
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PMID:Bacterial-like energy metabolism in the amitochondriate protozoon Hexamita inflata. 1270 92

During 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of human promyelocytic leukemia HL-60 cells toward maturing monocytes/macrophages, asparagine synthetase (ASNS) mRNA expression declined time and dose-dependently. The effect of TPA was inhibited by inhibitors for PKC and MEK 1/2, but not by those for JNK and p38 MAPK. Combination treatment with TPA and asparaginase synergistically enhanced the growth retardation accompanied by apoptotic cell death characterized by internucleosomal DNA fragmentation. These data suggest the possible involvement of MEK1/2 MAPK in the inhibitory effect of TPA on ASNS mRNA expression and that the induction of the down-regulation of ASNS (via MEK1/2 activation) may be a new strategy for the treatment of leukemia blast cells.
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PMID:Declined asparagine synthetase mRNA expression and enhanced sensitivity to asparaginase in HL-60 cells committed to monocytic differentiation. 1941 79

Mycosis fungoides (MF), a low-malignant lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. The current study reported a case of syringotropic MF, a rare variant of MF, which presented with reactive B cell proliferation, lymphoid follicle formation, hair loss and lymphadenopathy. The clinical manifestations of the patient were MF-like lumps. Immunohistochemical staining of AE1/AE3 showed that there were abundant infiltrated lymphocytes surrounding the syringocystadenoma. In addition, the direction of the lymphocyte arrangement was consistent with the meandering direction of syringocystadenoma. The patient did not respond to 1-month narrowband (311-nm) ultraviolet therapy; however, a good response was obtained subsequent to one cycle of chemotherapy with vincristine sulfate, etoposide, L-asparaginase and prednisone acetate (know as the VELP regimen). After 7 days of VELP chemotherapy, the skin lesions were ameliorated, hair loss was improved and lymphadenopathy disappeared. No lymphadenopathy or new skin lesions were observed during 6 months of follow-up.
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PMID:Syringotropic mycosis fungoides responding well to VELP chemotherapy: A case report. 2731 68


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