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MetaCyc Pathway: L-arginine degradation I (arginase pathway)
Inferred from experiment

Enzyme View:

Pathway diagram: L-arginine degradation I (arginase pathway)

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.

Synonyms: L-arginase degradative pathway, L-glutamate biosynthesis

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-glutamate Biosynthesis
Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-arginine Degradation

Some taxa known to possess this pathway include : Agrobacterium tumefaciens, Arabidopsis thaliana col, Bacillus licheniformis, Bacillus subtilis, Homo sapiens, Pinus sylvestris, Sulfolobus solfataricus, Thermus aquaticus, [Bacillus] caldovelox

Expected Taxonomic Range: Archaea, Bacteria , Embryophyta, Metazoa

General Background

Arginase-mediated L-arginine degradation is widely distributed in the biosphere, and is found in all primary kingdoms [Jenkinson96]. The first step in this process, catalyzed by the enzyme arginase, is the hydrolysis of L-arginine to form L-ornithine and urea.

There are many variations of the arginase pathway, since the fate of the products of the arginase reaction may be different in different organisms. Variants of arginase-based L-arginine-degradation pathways include L-arginine degradation I (arginase pathway), L-arginine degradation VI (arginase 2 pathway), and L-arginine degradation VII (arginase 3 pathway).

About This Pathway

This variant is the "classical" arginase pathway, having the widest distribution. The pathway is found in mammals as well as many bacteria. In this pathway L-arginine is converted into L-glutamate in a series of three steps; following the initial step, catalyzed by arginase, L-ornithine is converted to L-glutamate-5-semialdehyde by ornithine aminotransferase (OAT). L-glutamate-5-semialdehyde undergoes a spontaneous conversion to (S)-1-pyrroline-5-carboxylate, which is then converted in the third step, catalyzed by Δ1-pyrroline-5-carboxylate dehydrogenase, mitochondrial, to L-glutamate. In a subsequent step glutamate dehydrogenase (GDH) removes the amino group from L-glutamate, generating 2-oxoglutarate, which is fed to the TCA cycle I (prokaryotic) (see L-glutamate degradation I). Such conversion into L-glutamate is a common route for the degradation of amino acids, including L-glutamine, L-histidine, and L-proline (see the pathways L-glutamine degradation I, L-histidine degradation I and L-proline degradation).

In mammals, the enzymes catalyzing the reactions of this pathway are present in the mitochondrial matrix. There are two isoforms of mammalian arginases - a mitochondrial form, including the humane arginase 2, and a cytosolic form, which includes the human arginase 1. The cytosolic arginases, however, are believed to be involved mostly in the urea cycle (see urea cycle) [SkrzypekOsiecka83], although this notion has been questioned [Cederbaum04]. Human arginases were found in many tissues, including kidney and prostate, brain, skeletal muscle, placenta, lung, mammary gland, macrophage, uterus, testis, and gut [Morris97, Cederbaum04].

In prokaryotes, this pathway is used for the catabolism of L-arginine as either a carbon or a nitrogen source. Arginases have been detected in and characterized from several species, including bacilii [Patchett91, Gardan95], agrobacteria [Vissers86, Dessaux86], cyanobacteria [Gupta79, Weathers78, Quintero00], Proteus spp. [Prozesky73], Thermus aquaticus [Degryse76], and mycobacteria [Zeller54]. However, in most of these cases the fate of L-ornithine is not known [Cunin86]. In some cases L-arginine can can be utilized by the organism as both carbon and nitrogen source, while in others it is used only as a nitrogen source. In addition, some organisms possess the enzyme urease, which converts the urea formed by arginase into carbon monoxide and ammonia, a favorite nitrogen source.

In some strains, such as Bacillus licheniformis, the pathway is subject to strong catabolite repression during growth on glucose [Laishley68]. In some strains, the pathway is also subject to nitrogen catabolite repression. Such regulation is species specific and is not universal [Schreier82].

Although this pathway was not originally believed to act in plants, later studies provided evidence for its existence [Funck08, Canas08]. For example, in Pinus sylvestris (Scots pine), this pathway appears to be required to provide the glutamate that is needed for glutamine biosynthesis during the early stages of seed germination [Canas08]. However, further work will be required to determine if this is the only pathway that operates in plants, or whether additional pathways such as L-arginine degradation VI (arginase 2 pathway) can also contribute to arginine degradation [Funck08, Roosens98].

Variants: L-arginine degradation II (AST pathway), L-arginine degradation III (arginine decarboxylase/agmatinase pathway), L-arginine degradation IV (arginine decarboxylase/agmatine deiminase pathway), L-arginine degradation V (arginine deiminase pathway), L-arginine degradation VI (arginase 2 pathway), L-arginine degradation VII (arginase 3 pathway), L-arginine degradation VIII (arginine oxidase pathway), L-arginine degradation IX (arginine:pyruvate transaminase pathway), L-arginine degradation X (arginine monooxygenase pathway), L-arginine degradation XI, L-arginine degradation XII, L-citrulline-nitric oxide cycle, L-glutamate and L-glutamine biosynthesis, L-glutamate biosynthesis I, L-glutamate biosynthesis II, L-glutamate biosynthesis III, L-glutamate biosynthesis IV, L-glutamate biosynthesis V, superpathway of L-arginine and L-ornithine degradation, superpathway of L-arginine, putrescine, and 4-aminobutanoate degradation

Created 09-Jul-1998 by Ying HC, SRI International
Revised 29-Sep-2005 by Caspi R, SRI International


Canas08: Canas RA, Villalobos DP, Diaz-Moreno SM, Canovas FM, Canton FR (2008). "Molecular and functional analyses support a role of Ornithine-{delta}-aminotransferase in the provision of glutamate for glutamine biosynthesis during pine germination." Plant Physiol 148(1);77-88. PMID: 18621980

Cederbaum04: Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P, Iyer RK (2004). "Arginases I and II: do their functions overlap?." Mol Genet Metab 81 Suppl 1;S38-44. PMID: 15050972

Cunin86: Cunin R, Glansdorff N, Pierard A, Stalon V (1986). "Biosynthesis and metabolism of arginine in bacteria." Microbiol Rev 1986;50(3);314-52. PMID: 3534538

Degryse76: Degryse E, Glansdorff N, Pierard A (1976). "Arginine biosynthesis and degradation in an extreme thermophile, strain Z05." Arch Int Physiol Biochim 84(3);599-601. PMID: 64178

Dessaux86: Dessaux Y, Petit A, Tempe J, Demarez M, Legrain C, Wiame JM (1986). "Arginine catabolism in Agrobacterium strains: role of the Ti plasmid." J Bacteriol 166(1);44-50. PMID: 3957872

Funck08: Funck D, Stadelhofer B, Koch W (2008). "Ornithine-delta-aminotransferase is essential for arginine catabolism but not for proline biosynthesis." BMC Plant Biol 8;40. PMID: 18419821

Gardan95: Gardan R, Rapoport G, Debarbouille M (1995). "Expression of the rocDEF operon involved in arginine catabolism in Bacillus subtilis." J Mol Biol 1995;249(5);843-56. PMID: 7540694

Gupta79: Gupta, M., Carr, N.G. (1979). "Enzymology of arginine metabolism in heterocyst forming cyanobacteria." FEMS Microbiol. Lett. 12: 179-181.

Jenkinson96: Jenkinson CP, Grody WW, Cederbaum SD (1996). "Comparative properties of arginases." Comp Biochem Physiol B Biochem Mol Biol 114(1);107-32. PMID: 8759304

Laishley68: Laishley EJ, Bernlohr RW (1968). "Regulation of arginine and proline catabolism in Bacillus licheniformis." J Bacteriol 96(2);322-9. PMID: 5674049

Morris97: Morris SM, Bhamidipati D, Kepka-Lenhart D (1997). "Human type II arginase: sequence analysis and tissue-specific expression." Gene 193(2);157-61. PMID: 9256072

Patchett91: Patchett ML, Daniel RM, Morgan HW (1991). "Characterisation of arginase from the extreme thermophile 'Bacillus caldovelox'." Biochim Biophys Acta 1077(3);291-8. PMID: 2029528

Prozesky73: Prozesky OW, Grabow WO, van der Merwe S, Coetzee JN (1973). "Arginine gene clusters in the Proteus-Providence group." J Gen Microbiol 77(1);237-40. PMID: 4579440

Quintero00: Quintero MJ, Muro-Pastor AM, Herrero A, Flores E (2000). "Arginine catabolism in the cyanobacterium Synechocystis sp. Strain PCC 6803 involves the urea cycle and arginase pathway." J Bacteriol 182(4);1008-15. PMID: 10648527

Roosens98: Roosens NH, Thu TT, Iskandar HM, Jacobs M (1998). "Isolation of the ornithine-delta-aminotransferase cDNA and effect of salt stress on its expression in Arabidopsis thaliana." Plant Physiol 117(1);263-71. PMID: 9576796

Schreier82: Schreier HJ, Smith TM, Bernlohr RW (1982). "Regulation of nitrogen catabolic enzymes in Bacillus spp." J Bacteriol 151(2);971-5. PMID: 6124533

SkrzypekOsiecka83: Skrzypek-Osiecka I, Robin Y, Porembska Z (1983). "Purification of rat kidney arginases A1 and A4 and their subcellular distribution." Acta Biochim Pol 30(1);83-92. PMID: 6408859

Vissers86: Vissers S, Legrain C, Wiame JM (1986). "Control of a futile urea cycle by arginine feedback inhibition of ornithine carbamoyltransferase in Agrobacterium tumefaciens and Rhizobia." Eur J Biochem 159(3);507-11. PMID: 3758074

Weathers78: Weathers PJ, Chee HL, Allen MM (1978). "Arginine catabolism in Aphanocapsa 6308." Arch Microbiol 118(1);1-6. PMID: 100070

Zeller54: Zeller EA, Van Orden LS, Vogtli W (1954). "Enzymology of mycobacteria. VII. Degradation of guanidine derivatives." J Biol Chem 209(1);429-35. PMID: 13192096

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

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Barrett87: Barrett DJ, Bateman JB, Sparkes RS, Mohandas T, Klisak I, Inana G (1987). "Chromosomal localization of human ornithine aminotransferase gene sequences to 10q26 and Xp11.2." Invest Ophthalmol Vis Sci 28(7);1037-42. PMID: 3596985

Brown92: Brown ED, Wood JM (1992). "Redesigned purification yields a fully functional PutA protein dimer from Escherichia coli." J Biol Chem 1992;267(18);13086-92. PMID: 1618807

BSUB93: "Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics." (1993). Editors: Sonenshein, A.L., Hoch, J.A., Losick, R. American Society For Microbiology, Washington, DC.

Cama03: Cama E, Colleluori DM, Emig FA, Shin H, Kim SW, Kim NN, Traish AM, Ash DE, Christianson DW (2003). "Human arginase II: crystal structure and physiological role in male and female sexual arousal." Biochemistry 42(28);8445-51. PMID: 12859189

Chen04: Chen H, McCaig BC, Melotto M, He SY, Howe GA (2004). "Regulation of plant arginase by wounding, jasmonate, and the phytotoxin coronatine." J Biol Chem 279(44);45998-6007. PMID: 15322128

Cho96: Cho K, Fuqua C, Martin BS, Winans SC (1996). "Identification of Agrobacterium tumefaciens genes that direct the complete catabolism of octopine." J Bacteriol 178(7);1872-80. PMID: 8606160

Cho97: Cho K, Fuqua C, Winans SC (1997). "Transcriptional regulation and locations of Agrobacterium tumefaciens genes required for complete catabolism of octopine." J Bacteriol 179(1);1-8. PMID: 8981973

Colleluori01: Colleluori DM, Morris SM, Ash DE (2001). "Expression, purification, and characterization of human type II arginase." Arch Biochem Biophys 389(1);135-43. PMID: 11370664

Cox01: Cox JD, Cama E, Colleluori DM, Pethe S, Boucher JL, Mansuy D, Ash DE, Christianson DW (2001). "Mechanistic and metabolic inferences from the binding of substrate analogues and products to arginase." Biochemistry 40(9);2689-701. PMID: 11258880

Delauney93: Delauney AJ, Hu CA, Kishor PB, Verma DP (1993). "Cloning of ornithine delta-aminotransferase cDNA from Vigna aconitifolia by trans-complementation in Escherichia coli and regulation of proline biosynthesis." J Biol Chem 268(25);18673-8. PMID: 8103048

Deuschle01: Deuschle K, Funck D, Hellmann H, Daschner K, Binder S, Frommer WB (2001). "A nuclear gene encoding mitochondrial Delta-pyrroline-5-carboxylate dehydrogenase and its potential role in protection from proline toxicity." Plant J 27(4);345-56. PMID: 11532180

Deuschle04: Deuschle K, Funck D, Forlani G, Stransky H, Biehl A, Leister D, van der Graaff E, Kunze R, Frommer WB (2004). "The role of [Delta]1-pyrroline-5-carboxylate dehydrogenase in proline degradation." Plant Cell 16(12);3413-25. PMID: 15548746

Di05: Di Costanzo L, Sabio G, Mora A, Rodriguez PC, Ochoa AC, Centeno F, Christianson DW (2005). "Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response." Proc Natl Acad Sci U S A 102(37);13058-63. PMID: 16141327

Forlani97: Forlani, Giuseppe, Scainelli, Damiano, Nielsen, Erik (1997). "Delta1-pyrroline-5-carboxylate dehydrogenase from cultured cells of potato." Plant Physiology 113:1413-1418. PMID: 12223682

ForteMcRobbie86: Forte-McRobbie CM, Pietruszko R (1986). "Purification and characterization of human liver "high Km" aldehyde dehydrogenase and its identification as glutamic gamma-semialdehyde dehydrogenase." J Biol Chem 261(5);2154-63. PMID: 3944130

ForteMcRobbie89: Forte-McRobbie C, Pietruszko R (1989). "Human glutamic-gamma-semialdehyde dehydrogenase. Kinetic mechanism." Biochem J 261(3);935-43. PMID: 2803253

Gardan97: Gardan R, Rapoport G, Debarbouille M (1997). "Role of the transcriptional activator RocR in the arginine-degradation pathway of Bacillus subtilis." Mol Microbiol 1997;24(4);825-37. PMID: 9194709

Geraghty98: Geraghty MT, Vaughn D, Nicholson AJ, Lin WW, Jimenez-Sanchez G, Obie C, Flynn MP, Valle D, Hu CA (1998). "Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia." Hum Mol Genet 7(9);1411-5. PMID: 9700195

Goodman74: Goodman SI, Mace JW, Miles BS, Teng CC, Brown SB (1974). "Defective hydroxyproline metabolism in type II hyperprolinemia." Biochem Med 10(4);329-36. PMID: 4851275

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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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