아스파라기나제

아스파라기나제
아스파라기나제 구조식 이미지
카스 번호:
9015-68-3
한글명:
아스파라기나제
동의어(한글):
아스파라기나제
상품명:
ASPARAGINASE
동의어(영문):
CL059;LASPAR;elspar;mk-965;leunase;paronal;l-asnase;kidrolase;crasnitin;colaspase
CBNumber:
CB2484567
분자식:
C14H17NO4S
포뮬러 무게:
295.35
MOL 파일:
Mol file

아스파라기나제 속성

알파
D20 -30 to -32°
저장 조건
2-8°C
물리적 상태
suspension
색상
결정 또는 분말
Merck
13,841
CAS 데이터베이스
9015-68-3
EPA
Asparaginase (9015-68-3)
안전
  • 위험 및 안전 성명
  • 위험 및 사전주의 사항 (GHS)
위험품 표기 T,Xn
위험 카페고리 넘버 61-42/43-63
안전지침서 53-22-36/37/39-45-36/37
유엔번호(UN No.) 3249
WGK 독일 3
RTECS 번호 CI9000000
F 고인화성물질 10-21
위험 등급 6.1(a)
포장분류 II
HS 번호 3507909090
유해 물질 데이터 9015-68-3(Hazardous Substances Data)
독성 TDLo ims-chd: 8145 iu/kg/1W:SYS CANCAR 34,780,74
그림문자(GHS): GHS hazard pictogramsGHS hazard pictograms
신호 어: Warning
유해·위험 문구:
암호 유해·위험 문구 위험 등급 범주 신호 어 그림 문자 P- 코드
H317 알레르기성 피부 반응을 일으킬 수 있음 피부 과민성 물질 구분 1 경고 GHS hazard pictograms P261, P272, P280, P302+P352,P333+P313, P321, P363, P501
H361 태아 또는 생식능력에 손상을 일으킬 것으로 의심됨 생식독성 물질 구분 2 경고 P201, P202, P281, P308+P313, P405,P501
예방조치문구:
P201 사용 전 취급 설명서를 확보하시오.
P280 보호장갑/보호의/보안경/안면보호구를 착용하시오.
P302+P352 피부에 묻으면 다량의 물로 씻으시오.
P308+P313 노출 또는 접촉이 우려되면 의학적인 조치· 조언를 구하시오.

아스파라기나제 C화학적 특성, 용도, 생산

순도시험

  (1) 비소 : 이 품목을 비소시험법에 따라 시험할 때, 그 양은 4.0ppm 이하이어야 한다.

  (2) 납 : 이 품목 5.0g을 취하여 원자흡광광도법 또는 유도결합플라즈마발광광도법에 따라 시험할 때, 그 양은 5.0ppm 이하이어야 한다.

  (3) 대장균군 : 이 품목은 「식품의 기준 및 규격」일반시험법의 미생물시험법 중 대장균군에 따라 시험할 때, 제품 1g당 30 이하이어야 한다.

  (4) 살모넬라 : 이 품목은 「식품의 기준 및 규격」일반시험법의 미생물시험법 중 살모넬라균시험법에 따라 시험할 때, 음성(-)이어야 한다.

  (5) 대장균 : 이 품목 25g을 취하여 「식품의 기준 및 규격」일반시험법의 미생물시험법 중 대장균에 따라 시험할 때, 음성(-)이어야 한다.

확인시험

  이 품목의 활성시험법에 따라 시험할 때 활성을 나타내어야 한다.

정의

  이 품목은 Aspergillus oryzae 및 Aspergillus niger의 배양물에서 얻어진 효소제이다. 다만, 역가조정, 품질보존 등을 위하여 희석제, 안정제 등을 첨가할 수 있다.

  이 품목은 L-아스파라진을 가수분해하여 L-아스파트산과 암모니아를 생성한다.

개요

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.

용도

Asparaginase from Escherichia coli has been used:

정의

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.

일반 설명

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 G1 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.

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.

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).

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.

부작용

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.

Safety Profile

Human (child) systemic effects byintramuscular route. An experimental teratogen. Otherexperimental reproductive effects. Questionablecarcinogen with experimental neoplastigenic data.

아스파라기나제 준비 용품 및 원자재

원자재

준비 용품


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