Asparaginase

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Asparaginase
Systematic (IUPAC) name
E. coli L-asparagine amidohydrolase
Identifiers
CAS number	9015-68-3
ATC code	L01XX02
PubChem	?
DrugBank	BTD00011
Chemical data
Formula	C1377H2208N382O442S17
Mol. mass	31731.9 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	8-30 hrs
Excretion	?
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status
Routes	?

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Asparaginase (EC 3.5.1.1) is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. It is also marketed under the brand names Elspar®, Oncaspar, and Erwinase to treat acute lymphoblastic leukemia (ALL) and is also used in some mast cell tumor protocols. ^[1] Unlike other chemotherapy agents, it can be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation.

Mechanism of action

The rationale behind asparaginase is that it takes advantage of the fact that ALL leukemic cells are unable to synthesize the non-essential amino acid asparagine whereas normal cells are able to make their own asparagine. These leukemic cells depend on circulating asparagine. Asparaginase however catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives the leukemic cell of circulating asparagine.

Side effects

The main side effect is an allergic or hypersensitivity reaction. Asparaginase has also been associated with pancreatitis. Additionally, it can also be associated with a coagulopathy as it decreases protein synthesis, including synthesis of coagulation factors and anticoagulant factor, leading to bleeding or thrombotic events such as stroke.

References

External links

• MeSH Asparaginase

[3] THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP; Educational Director, VeterinaryPartner.com

v • d • e Chemotherapeutic agents/Antineoplastic agents (L01)
Alkylating and alkylating-like agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Bendamustine, Uramustine) Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin) Platinum (alkylating-like): (Carboplatin, Cisplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin) Alkyl sulfonates:(Busulfan, Treosulfan) Hydrazines:(Procarbazine, Dacarbazine, Temozolomide) Aziridines:(ThioTEPA)
Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine) Pyrimidine:(Capecitabine, Cytarabine, Decitabine, Fluorouracil, Floxuridine, Gemcitabine)
Spindle poison/mitotic inhibitor	Taxane: (Docetaxel, Larotaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).
Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Pixantrone, Valrubicin) streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) - Hydroxyurea
Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan, Rubitecan), Podophyllum:(Etoposide, Teniposide)
CI monoclonal antibodies	Receptor tyrosine kinase (Cetuximab, Panitumumab, Trastuzumab) - CD20 (Rituximab, Tositumomab) - other (Alemtuzumab, Bevacizumab, Gemtuzumab)
Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin
Tyrosine kinase inhibitors	Axitinib, Bosutinib, Cediranib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Lestaurtinib, Nilotinib, Semaxanib, Sorafenib, Sunitinib, Vandetanib
Cyclin-dependent kinase inhibitor	Seliciclib
Other	retinoids (Alitretinoin, Tretinoin), Fusion protein (Aflibercept) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase (Pegaspargase), Bexarotene, Bortezomib, Celecoxib, Denileukin diftitox, Elesclomol, Estramustine, Irofulven, Ixabepilone, Masoprocol, Mitotane, Oblimersen, Testolactone, Tipifarnib, Trabectedin

v • d • e Carbon-nitrogen non-peptide hydrolases (EC 3.5)
3.5.1 - Amidohydrolases	Asparaginase - Glutaminase - Urease - Biotinidase - Aspartoacylase - Ceramidase -Aspartylglucosaminidase - Fatty acid amide hydrolase - Histone deacetylase (Sirtuin)
3.5.2	Barbiturase - Beta-lactamase
3.5.3	Arginase
3.5.4 - Aminohydrolases	Guanine deaminase - Adenosine deaminase - AMP deaminase - Inosine monophosphate synthase - DCMP deaminase - GTP cyclohydrolase I
Other	Nitrilase - Thiaminase II

v • d • e Amino acid metabolism enzymes (essential in CAPS)
K	LYSINE→acetyl-CoA Saccharopine dehydrogenase - Glutaryl-CoA dehydrogenase LEUCINE→acetyl-CoA Branched-chain alpha-keto acid dehydrogenase complex - Isovaleryl coenzyme A dehydrogenase - Methylcrotonyl-CoA carboxylase TRYPTOPHAN→acetyl-CoA Kynureninase PHENYLALANINE→tyrosine→acetoacetate (see below)
G	glycine→serine→pyruvate→TCA Serine hydroxymethyltransferase - Serine dehydratase alanine→pyruvate→TCA Alanine transaminase cysteine→pyruvate→TCA D-cysteine desulfhydrase threonine→pyruvate→TCA L-threonine dehydrogenase HISTIDINE→glutamate Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase proline→glutamate Proline oxidase - Pyrroline-5-carboxylate reductase - 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 - PYCR1 arginine→glutamate Ornithine aminotransferase - Ornithine decarboxylase - Agmatinase glutamate→alpha-ketoglutarate→TCA Glutamate dehydrogenase METHIONINE→propionyl-CoA Methionine adenosyltransferase - Adenosylhomocysteinase - (or MTR/Homocysteine methyltransferase) - Cystathionine beta synthase - Cystathionine gamma-lyase ISOLEUCINE/valine→propionyl-CoA Branched-chain alpha-keto acid dehydrogenase complex
NT	HISTIDINE→histamine Histidine decarboxylase tyrosine→dopamine→epinephrine Tyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase - Catechol-O-methyl transferase glutamate→GABA Glutamate decarboxylase arginine→NO Nitric oxide synthase
Other	tyrosine→melanin Tyrosinase TRYPTOPHAN→serotonin→melatonin Tryptophan hydroxylase - Aromatic L-amino acid decarboxylase - Acetylserotonin O-methyltransferase cysteine+glutamate→glutathione Gamma-glutamylcysteine synthetase - Glutathione synthetase glycine→creatine Guanidinoacetate N-methyltransferase - Creatine kinase glutamate→glutamine Glutamine synthetase - Glutaminase collagen Prolyl hydroxylase - Lysyl hydroxylase
see also disorders, intermediates

de:Asparaginase

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .