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MetaCyc Pathway: L-asparagine degradation I
Inferred from experimentTraceable author statement to experimental support

Enzyme View:

Pathway diagram: L-asparagine degradation I

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-asparagine Degradation

Some taxa known to possess this pathway include : Dickeya chrysanthemi, Escherichia coli K-12 substr. MG1655, Hordeum vulgare, Lupinus albus, Neonectria obtusispora, Pectobacterium carotovorum, Pisum sativum, Thermus thermophilus, Vicia faba, Zea mays

Expected Taxonomic Range: Archaea, Bacteria , Fungi, Metazoa, Viridiplantae

General Background

L-Asparagine is hydrolyzed to L-aspartate and ammonia by the enzyme asparaginase [Voet04]. The enzyme has been characterized from diverse sources, including bacteria, archaea [Yao05], fungi [Sinclair94, Kil95, Raha90], ciliates [Tsavdaridis94] and plants [Sodek80]. It has also been characterized from the liver and serum of guinea pigs [Zhang95].

The enzyme has anti-tumor activity and purified L-asparaginase from Escherichia coli K-12 and Dickeya chrysanthemi have been used clinically to treat lymphoblastic leukemia and lymphosarcoma (in [Kotzia05]). The enzyme from some species contains glutaminase activity, believed to cause clinical side-effects. Enzyme preparations from species with decreased glutaminase activity, such as Pectobacterium carotovorum (previously known as Erwinia carotovora) have been characterized as potential therapeutics [Kotzia05].

Asparagine Degradation in Plants

Asparagine is the first amino acid discovered in plants, where it is the major nitrogen transport and storage compound. Asparagine is metabolized in plants in two routes, either via asparaginase (this pathway|) or via asparagine aminotransferase (see L-asparagine degradation II). Studies in pea suggested that the predominant route differs in different tissues. The asparaginase pathway predominates in seeds, whereas the aminotransferase pathway predominates in leaves [Ireland81].

In the asparaginase pathway, as depicted here, asparagine is deaminated to release aspartate and ammonia. The liberated ammonia is reassimilated and utilized for synthesis of all nitrogen containing compounds of the cell and in particular the amino acids. There is no evidence that aspartate is metabolized further in plants.

Variants: L-asparagine degradation II, L-asparagine degradation III (mammalian)

Unification Links: EcoCyc:ASPARAGINE-DEG1-PWY

Revised 05-Mar-2007 by Fulcher CA, SRI International


Ireland81: Ireland, Robert, Joy, Kenneth "Two routes for asparagine metabolism in Pisum sativum." Planta, 1981, 151:289-292.

Kil95: Kil JO, Kim GN, Park I (1995). "Extraction of extracellular L-asparaginase from Candida utilis." Biosci Biotechnol Biochem 59(4);749-50. PMID: 7772845

Kotzia05: Kotzia GA, Labrou NE (2005). "Cloning, expression and characterisation of Erwinia carotovora L-asparaginase." J Biotechnol 119(4);309-23. PMID: 15951039

Raha90: Raha SK, Roy SK, Dey SK, Chakrabarty SL (1990). "Purification and properties of an L-asparaginase from Cylindrocarpon obtusisporum MB-10." Biochem Int 21(6);987-1000. PMID: 2080924

Sinclair94: Sinclair K, Warner JP, Bonthron DT (1994). "The ASP1 gene of Saccharomyces cerevisiae, encoding the intracellular isozyme of L-asparaginase." Gene 144(1);37-43. PMID: 8026756

Sodek80: Sodek, Ladaslav, Lea, Peter, Miflin, Benjamin "Distribution and properties of a potassium-dependdent asparaginase isolated from developing seeds of Pisum sativa and other plants." Plant Physiology, 1980, 65:22-26.

Tsavdaridis94: Tsavdaridis IK, Triantafillidou DC, Kyriakidis DA (1994). "Two forms of L-asparaginase in Tetrahymena thermophila." Biochem Mol Biol Int 32(1);67-77. PMID: 8012291

Voet04: Voet D, Voet JG (2004). "Biochemistry, 3rd Edition." John Wiley & Sons Inc.

Yao05: Yao M, Yasutake Y, Morita H, Tanaka I (2005). "Structure of the type I L-asparaginase from the hyperthermophilic archaeon Pyrococcus horikoshii at 2.16 angstroms resolution." Acta Crystallogr D Biol Crystallogr 61(Pt 3);294-301. PMID: 15735339

Zhang95: Zhang N, Clarke F, Di Trapani G, Keough D, Beacham I (1995). "Guinea pig serum L-asparaginase: purification, and immunological relationship to liver L-asparaginase and serum L-asparaginases in other mammals." Comp Biochem Physiol B Biochem Mol Biol 112(4);607-12. PMID: 8590375

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Aghaiypour01: Aghaiypour K, Wlodawer A, Lubkowski J (2001). "Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu?." Biochim Biophys Acta 1550(2);117-28. PMID: 11755201

Aghaiypour01a: Aghaiypour K, Wlodawer A, Lubkowski J (2001). "Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase." Biochemistry 40(19);5655-64. PMID: 11341830

Aung00: Aung HP, Bocola M, Schleper S, Rohm KH (2000). "Dynamics of a mobile loop at the active site of Escherichia coli asparaginase." Biochim Biophys Acta 1481(2);349-59. PMID: 11018727

Bahreini14: Bahreini E, Aghaiypour K, Abbasalipourkabir R, Goodarzi MT, Saidijam M, Safavieh SS (2014). "An optimized protocol for overproduction of recombinant protein expression in Escherichia coli." Prep Biochem Biotechnol 44(5);510-28. PMID: 24219068

Bonthron90: Bonthron DT (1990). "L-asparaginase II of Escherichia coli K-12: cloning, mapping and sequencing of the ansB gene." Gene 1990;91(1);101-5. PMID: 2144836

Borek00: Borek D, Jaskolski M (2000). "Crystallization and preliminary crystallographic studies of a new L-asparaginase encoded by the Escherichia coli genome." Acta Crystallogr D Biol Crystallogr 2000;56 ( Pt 11);1505-7. PMID: 11053866

Borek04: Borek D, Michalska K, Brzezinski K, Kisiel A, Podkowinski J, Bonthron DT, Krowarsch D, Otlewski J, Jaskolski M (2004). "Expression, purification and catalytic activity of Lupinus luteus asparagine beta-amidohydrolase and its Escherichia coli homolog." Eur J Biochem 271(15);3215-26. PMID: 15265041

Borek14: Borek D, Kozak M, Pei J, Jaskolski M (2014). "Crystal structure of active site mutant of antileukemic L-asparaginase reveals conserved zinc-binding site." FEBS J 281(18);4097-111. PMID: 25040257

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Cantor09: Cantor JR, Stone EM, Chantranupong L, Georgiou G (2009). "The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta-aspartyl peptidase activity." Biochemistry 48(46);11026-31. PMID: 19839645

Cedar67: Cedar H, Schwartz JH (1967). "Localization of the two-L-asparaginases in anaerobically grown Escherichia coli." J Biol Chem 242(16);3753-5. PMID: 4962587

Cedar68: Cedar H, Schwartz JH (1968). "Production of L-asparaginase II by Escherichia coli." J Bacteriol 96(6);2043-8. PMID: 4881701

Chesney83: Chesney RH (1983). "E. coli L-asparaginase II production in the presence and absence of catabolite activating protein." FEMS Microbiol Lett 17(1-3):161-162.

Del83: Del Casale T, Sollitti P, Chesney RH (1983). "Cytoplasmic L-asparaginase: isolation of a defective strain and mapping of ansA." J Bacteriol 154(1);513-5. PMID: 6339481

Derst00: Derst C, Henseling J, Rohm KH (2000). "Engineering the substrate specificity of Escherichia coli asparaginase II. Selective reduction of glutaminase activity by amino acid replacements at position 248." Protein Sci 9(10);2009-17. PMID: 11106175

Derst92: Derst C, Henseling J, Rohm KH (1992). "Probing the role of threonine and serine residues of E. coli asparaginase II by site-specific mutagenesis." Protein Eng 5(8);785-9. PMID: 1287659

Derst94: Derst C, Wehner A, Specht V, Rohm KH (1994). "States and functions of tyrosine residues in Escherichia coli asparaginase II." Eur J Biochem 224(2);533-40. PMID: 7925369

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gesto13: Gesto DS, Cerqueira NM, Fernandes PA, Ramos MJ (2013). "Unraveling the enigmatic mechanism of L-asparaginase II with QM/QM calculations." J Am Chem Soc 135(19);7146-58. PMID: 23544711

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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