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

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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)

Maximum L-asparaginase activity was obtained when 1.0% lactose and 1.5% yeast extract were supplied as carbon and nitrogen sources, respectively. Glucose inhibited the enzyme formation. The diauxie phenomenon was observed with Erwinia aroideae NRRL B-138 grown in a medium containing glucose and lactose.
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PMID:L-Asparaginase synthesis by Erwinia aroideae. 502 78

Ten children with acute lymphocytic leukemia developed transient diabetes mellitus during treatment with L-asparaginase and prednisone. Serum glucose, plasma insulin, and plasma glucagon levels were measured when the patients were hyperglycemic. Six of the children were restudied several months later when there were no clinical or laboratory signs of glucose intolerance. Hyperglycemia induced by L-asparaginase and prednisone was associated with depression of plasma insulin and, despite the inhibiting action of L-asparaginase on protein synthesis, a corresponding elevation of plasma glucagon. Thus patients with diabetes mellitus induced by L-asparaginase and prednisone have relative hyperglucagonemia similar to other patients with diabetes mellitus.
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PMID:Relative hyperglucagonemia in L-asparaginase-and prednisone-induced glucose intolerance in management of acute lymphocytic leukemia. 634 Sep 6

Asparaginase II of Saccharomyces cerevisiae is a cell wall mannan containing glycoprotein. Recent studies have demonstrated that asparaginase II activity increases in exponentially growing cell cultures and then decreases as the cells enter the stationary phase. Enzyme inactivation has been attributed to a Zn2+-dependent protease which is synthesized de novo during the late exponential phase [Pauling, K.D., & Jones, G.E. (1980) J. Gen. Microbiol. 117, 423-430; Pauling, K.D., & Jones, G.E. (1980) Biochim. Biophys. Acta 616, 271-282]. We have investigated the mechanism of asparaginase II inactivation using both whole cell suspensions and highly purified enzyme. Our data indicate that the rate of asparaginase II inactivation in cell suspensions is primarily influenced by pH changes that occur as a consequence of cell growth and glucose fermentation and that enzyme inactivation is not dependent on Zn2+ or on de novo protein synthesis. Also, in vitro studies with purified enzyme show kinetics of inactivation that are similar to those observed in vivo. Consequently, involvement of a yeast protease in the inactivation process is relatively unlikely.
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PMID:Asparaginase II of Saccharomyces cerevisiae: comparison of enzyme stability in vivo and in vitro. 634 51

The glycemic and insulin response to an oral glucose load was studied in 17 children with acute lymphoblastic leukemia (ALL) and 13 normal controls. The patients were randomly assigned to either group A, receiving prednisone and vincristine, or group B, receiving these agents and, in addition, L-asparaginase from days 9-19 of the study. The glucose load was performed prior to (phase I), and on days 8 (phase II), and 19 (phase III) of chemotherapy. The mean glycemic response in both groups of patients was significantly higher than in controls at diagnosis and prior to any treatment, while mean insulin levels were not significantly different from controls. One week after initiation of treatment, the mean glycemic response improved, and was associated with hyperinsulinism. After the second week of treatment, the mean glucose and insulin response curves in group A were similar to controls. In group B, while insulin values returned to normal, blood glucose levels remained higher than in controls, but not significantly so. These findings suggest that: 1) The leukemic process itself, through mechanisms as yet undetermined, causes impairment of glucose tolerance, and 2) the diabetogenic effect of L-asparaginase is not manifested in all patients.
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PMID:Abnormal glucose tolerance in children with acute leukemia. Effect of induction chemotherapy including L-asparaginase. 635 58

The diabetogenic effect of daily injections of 1000 i.u./kg body wt. E coli L-asparaginase was studied in male New Zealand white rabbits and compared with the diabetogenic effect of a single bolus of 10,000 I.U. E coli L-asparaginase/kg body wt. to determine whether the schedule of administration of the drug altered the diabetic syndrome produced. A daily injection of 1000 i.u. L-asparaginase/kg. body wt. was continued for 30 days. During this time glucose levels in rabbits allowed free access to food rose steadily, reaching levels of 717 +/- 63 mg/dl the day after the last injection. Levels of immunoreactive insulin fell, reaching their nadir, 53 +/- 4 pg/ml (approximately 50% of baseline) at 25 days. Glucose levels declined when therapy was discontinued, but remained significantly above control levels 46 days after insulin injections were stopped. (Glucose levels in L-asparaginase-treated groups vs. those in controls on day 46 after discontinuation: 116 +/- 3 vs. 104 +/- 1 mg/dl; P less than 0.0025.) Levels of immunoreactive insulin rose when therapy ended, reaching control levels 17 days after discontinuation. In contrast, a single bolus injection of 10,000 I.U. L-asparaginase/kg resulted in hyperglycemia with hyperinsulinemia. These data suggest that L-asparaginase can induce either a hypoinsulinemic or a hyperinsulinemic diabetic syndrome depending on the schedule of administration of the L-asparaginase and that a mild abnormality in glucose homeostasis persists after discontinuation of L-asparaginase therapy.
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PMID:L-Asparaginase diabetes mellitus in rabbits: differing effects of two different schedules of L-asparaginase administration. 639 68

Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.
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PMID:Glucose metabolism in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules. 644 22

Glucose induced insulin release, from collagenase isolated islets of Langerhans obtained from non diabetic male New Zealand White rabbits, was inhibited in vitro by E. coli L-asparatinase. This inhibition was time and dose dependent with maximal inhibition being attained after 1 1/2 hr incubation using a dose of 1000 I.U. L-asparaginase/ml. Tolbutamide potentiated glucose-induced insulin release in the presence of inhibitory doses of the L-asparaginase. This potentiation was decreased at higher dose levels of L-asparaginase. L-leucine, L-arginine and theophylline also potentiated glucose-induced insulin release in the presence of L-asparaginase. This potentiation was intact in the presence of all doses of L-asparaginase tested. Glucose induced insulin release, from collagense isolated islets obtained from male New Zealand White rabbits rendered hypoinsulinemic and diabetic by daily intravenous injections of L-asparaginase in vivo, was similar to that of islets of non diabetic control rabbits when the islets were incubated in vitro in te absence of L-asparaginase. These data suggest that the hypoinsulinemic diabetic syndrome produced by the anti-tumor enzyme, L-asparaginase, is produced at least in part by the suppression of insulin release and that this suppression requires the enzyme to be present.
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PMID:E. coli L-asparaginase and insulin release in vitro. 675 34

The effect of arginine infusion on blood glucose and plasma levels of insulin, C-peptide and glucagon has been studied in leukemic children before and after treatment with L-asparaginase (10,000 U/m2/day for 10 days). Therapy induced a significant reduction in basal and peak blood glucose, insulin and C-peptide levels, while glucagon was unmodified. The conserved C-peptide-insulin molar ratio suggests the interference of L-asparaginase with proinsulin synthesis. In conclusion our results prove a decreased insulin reserve with a preserved, although reduced, beta-cell function.
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PMID:Pancreatic endocrine function in leukemic children treated with L-asparaginase. 676 89

Twenty-seven male New Zealand White rabbits were injected with a single dose of 10,000 IU E. coli L-asparaginase per kilogram body wt to document the diabetogenic activity of this antitumor agent. Significant weight loss was observed by day 1, and a loss continued until day 9. After day 16, weight steadily increased. Random serum glucose levels increased steadily after the injection of L-asparaginase, reaching a peak value of 344 +/- 32 mg/dl (x- +/- SEM) on day 10. From day 12, levels declined, but they remained significantly higher than basal levels. Serum immunoreactive insulin (IRI) levels had a similar pattern of response. By day 2 the IRI was significantly above baseline. The IRI levels increased daily, reaching a peak level of 1,379 +/- 587 pg/ml (x- +/- SEM). Thereafter the levels fell gradually. However, the IRI levels remained significantly higher than basal levels. Intravenous regular insulin decreased glucose levels in L-asparaginase-treated animals at 3 h by only 7.7 +/- 3.2%, while it decreased them in controls by 34.0 +/- 6.7% (P less than 0.0025). These data demonstrate that, acutely, a single intravenous dose of 10,000 IU E. coli L-asparaginase per kilogram body wt induces a hyperinsulinemic. Insulin-resistant, diabetic syndrome in rabbits.
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PMID:L-Asparaginase-induced diabetes mellitus in rabbits. 699 39

Male New Zealand White Rabbits were injected intravenously with either a single dose of 10,000 IU Escherichia coli L-asparaginase/kg body weight containing 80 mg of D-mannitol/10,000 IU E. coli L-asparaginase or 80 mg D-mannitol kg/body weight alone. Elevated fasting glucose (G) and elevated fasting immunoreactive insulin (IRI) levels were observed in the L-asparaginase treated rabbits at 1 wk. They peaked at 3 wk and declined thereafter. However, fasting G and IRI levels remained significantly elevated at the end of the study (9-15 wk after injection) compared to preinjection levels and levels of the controls. Glucose and IRI levels 0.5 hr post and intravenous glucose load (1 g/kg body weight) also became elevated post L-asparaginase and followed a time course similar to that of the fasting G and IRI levels. These 0.5-hr levels also remained significantly elevated at the end of the study. These data show that a single dose of 10,000 IU/kg body weight produced a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9-15 week.
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PMID:Glucose tolerance an insulin release in L-asparaginase treated rabbits. 700 18


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