Asparaginase Chemische Eigenschaften,Einsatz,Produktion Methoden
R-S?tze Betriebsanweisung:
R61:Kann das Kind im Mutterleib sch?digen.
R42/43:Sensibilisierung durch Einatmen und Hautkontakt m?glich.
R63:Kann das Kind im Mutterleib m?glicherweise sch?digen.
S-S?tze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S22:Staub nicht einatmen.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn m?glich, dieses Etikett vorzeigen).
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
Beschreibung
Using the enzyme asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1), it is
possible to significantly reduce the formation of the cooking carcinogen acrylamide
during roasting, deep-frying, or baking of foods. The enzyme hydrolyzes
free asparagine to aspartic acid, thereby preventing the formation of
acrylamide by reaction of asparagine with reducing sugars at elevated temperatures
during the Maillard reaction.
The mitigation of acrylamide formation is especially important for a number of
cereal- and potato-based products, including crackers, crispbread, gingerbread,
biscuits, French fries, and potato chips. After asparaginase pretreatment, the
acrylamide concentration of certain foods could be reduced by up to 97 % [84, 86].
By means of in vitro directed evolution, the properties of asparaginase were
optimized. For example, an Asp133Leu mutation of a wild-type enzyme showed a
significantly improved thermal stability. The enzyme’s half-life at 50 C increased
from 3 to 160 h, and the half-inactivation temperature of the mutant was 9 C
higher.
Verwenden
Asparaginase from
Escherichia coli has been used:
- to compare the cytotoxic effect of L-asparaginase purified from?Streptomyces brollosae?NEAE-115
- as a standard in asparaginase assay to quantify asparaginase activities in various eel tissues
- to elicit amino acid deprivation
Definition
An enzyme used in the treatment of
certain types of leukemia. Produced by biochemical
activity of certain bacteria, yeasts, and fungi. Yields
are in excess of 3500 units/g of source.
Indications
The enzyme L-asparaginase (Elspar) is derived from the
bacteria Escherichia coli and Erwinia carotovora. It catalyzes
the hydrolysis of L-asparagine to aspartic acid and
ammonia. L-Glutamine also can undergo hydrolysis by
this enzyme, and during therapy, the plasma levels of both
amino acid substrates fall to zero.Tumor cells sensitive to
L-asparaginase are deficient in the enzyme asparagine
synthetase and therefore cannot synthesize asparagine.
Depletion of exogenous asparagine and glutamine inhibits
protein synthesis in cells lacking asparagine synthetase,
which leads to inhibition of nucleic acid synthesis and cell
death.
Allgemeine Beschreibung
Asparaginase is available in 10-mL vials for intramuscularand IV use in the treatment of acute lymphocytic leukemia.
Tumor cells are unable to synthesize asparagine, and thereforemust utilize what is available in the extracellular environment.The agent acts by hydrolyzing extracellular asparagineto aspartate and ammonia. The tumor cells are then deprivedof a necessary nutrient, and protein synthesis is inhibited leadingto cell death. The agent is specific for the G
1 phase of thecell cycle. Resistance occurs because of the development ofthe tumor cells ability to produce asparagine synthetase thatallows them to synthesize the required amino acid. Antibodyproduction directed at asparaginase may be stimulated by theagent as well. The agent remains in the extracellular spaceafter parental administration and is 30% protein bound. Themetabolism of the agent has not been well characterized andthe plasma half-life depends on the formulation of the drug.The E. coli-derived agent has a plasma half-life of 40 to 50hours, whereas polyethylene glycol-asparaginase’s half-life is3 to 5 days. Adverse effects include hypersensitivity reactions,fever, chills, nausea, lethargy, confusion, hallucinations,and possibly coma. Myelosuppression is not generallyseen. An increased risk of bleeding and clotting is seen in halfof the patients taking the agent.
Biotechnological Applications
L-asparaginase (EC. 3.5.1.1; asparagine amidohydrolase) catalyzes the hydrolysis of L-Asparagine to L-aspartic acid and ammonia. This enzyme is used for the treatment of selected types of hemopoietic diseases such as acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphomas (Pieters et al. 2011; Rytting 2012). It is also a model enzyme for the development of new drug delivery system and L-asparagine biosensor for leukemia. This enzyme was used in the food industry for the production of acrylamide free food (Kumar and Verma 2012; Dhanam Jayam and Kannan 2013).
Y. lipolytica is a potential producer of L-asparaginase. However, there are very few reports on L-asparaginase production by the yeast. Karanam and Medicherla optimized L-asparaginase production of Y. lipolytica NCIM 3472 in solid-state fermentation (SSF) using palm kernel cake as the substrate. The maximum L-asparaginase activity at optimum conditions was near 40 U/g of the initial dry substrate (U/gds) (Karanam and Medicherla 2010).
Mechanism of action
The half-life of L-asparaginase in human plasma is 6
to 30 hours.The drug remains primarily in the intravascular
space, so its volume of distribution is only slightly
greater than that of the plasma. Metabolism and disposition
are thought to occur through serum proteases, the
reticuloendothelial system, and especially in patients
with prior exposure to the drug, binding by antibodies.
The drug is not excreted in urine, and very little appears
in the CSF.
Clinical Use
Pegaspargase, a polyethylene glycol conjugate of L-asparaglnase (ASNase),
was launched for combination chemotherapy in acute lymphoblastic leukemia (ALL).
L-Asparaginase is an enzyme that inhibits protein synthesis by the depletion of
sources of L-asparagine, which is necessary for transformed lymphoid cells to
proliferate. It has been used as a standard component of the antileukemia
armamentarium for childhood All. Pegaspargase has greater antitumor activity, a
longer plasma half-life and less immunogenicity than ASNase. It produces minimal
side effects after repeated dosing, whereas ASNase induces anaphylactic shock,
urticaria, anorexia or vomiting and acute pancreatitis in dogs, and other
immunological effects in man resulting from sensitization to the enzyme or protein synthesis inhibition. The efficacy of pegaspargase for other indications including
breast and lung cancers, non-Hodgkin's lymphoma and pancreatic cancer has been
reported.
Anticancer Research
Both the commonly known and distinctive species have been reported to produceL-asparaginase. The common species of endophytes, which produce L-asparaginase,include Fusarium sp., Penicillium sp., and Colletotrichum sp. They are isolated asendophytes from a variety of medicinal plants (Audipudi et al. 2014; El-Said et al.2016).
Chow and Ting (2015) studiedL-asparaginase production from fungal endophytes isolated from anticancer plantsin Malaysia. They found Fusarium oxysporum and Penicillium simplicissimumfrom Murraya koenigii and Pereskia bleo, respectively, as effective producers ofL-asparaginase. In addition to L-asparaginase, endophytes from anticancer plantshave also been established as producers of other valuable anticancer, antimicrobial,and antioxidant compounds. This is further supported by many reports on discoveryof these anticancer agents in different species of endophytic fungi either from sameor different host plants.
Nebenwirkungen
Since it is a foreign protein, L-asparaginase may produce
hypersensitivity reactions, including urticarial skin
rashes and severe anaphylactic reactions. One-third of
patients have nausea, anorexia, weight loss, and mild
fever. Almost all patients develop elevated serum
transaminases and other biochemical indices of hepatic
dysfunction. Severe hepatic toxicity occurs in fewer
than 5% of cases. Patients receiving L-asparaginase may
develop symptoms of CNS toxicity, including drowsiness,
confusion, impaired mentation, and even coma.
Pancreatitis occurs in 5 to 10% of cases.Hyperglycemia,
possibly due to inhibition of insulin synthesis, also may
occur. L-Asparaginase differs from most cytotoxic drugs
in its lack of toxicity to bone marrow, gastrointestinal
tract, and hair follicles.
Sicherheitsprofil
Human (child) systemic effects byintramuscular route. An experimental teratogen. Otherexperimental reproductive effects. Questionablecarcinogen with experimental neoplastigenic data.
Asparaginase Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
