MetaCyc Pathway: L-arginine degradation VI (arginase 2 pathway)
Inferred from experiment

Enzyme View:

Pathway diagram: L-arginine degradation VI (arginase 2 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-proline biosynthesis from arginine

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

Some taxa known to possess this pathway include : Saccharomyces cerevisiae, Synechocystis sp. PCC 6803

Expected Taxonomic Range: Cyanobacteria, Fungi, Viridiplantae

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

The preferred nitrogen sources of Saccharomyces cerevisiae are ammonia, L-asparagine, and L-glutamine. However, if these sources are not available, Saccharomyces cerevisiae is able to utilize arginine as its sole nitrogen source.

Earlier work has established that Saccharomyces cerevisiae converts L-arginine via L-ornithine to L-glutamate-5-semialdehyde, which undergoes a spontaneous cyclization reaction, forming (S)-1-pyrroline-5-carboxylate (P5C). This sequence of reactions is identical to the "classical" arginase pathway (see L-arginine degradation I (arginase pathway)) [Middlehoven64]. However, while in the "classical" pathway P5C is coverted to L-glutamate, it was shown that in Saccharomyces cerevisiae it is converted to L-proline by the enzyme P5C reductase [Brandriss80]. The L-proline that is formed is then catabolized to L-glutamate by the normal L-proline degradation pathway (see L-proline degradation).

Since P5C is also an intermediate in the L-proline degradation pathway, it occurs twice in the path from L-arginine to L-glutamate. Thus P5C can be converted to either L-glutamate (by the enzyme Δ1-pyrroline-5-carboxylate dehydrogenase) or to L-proline by P5C reductase [Brandriss80]. Futile cycling between L-proline and P5C is prevented by subcellular compartmentalization - while Δ1-pyrroline-5-carboxylate dehydrogenase is a mitochondrial enzyme, P5C reductase is located in the cytoplasm [Brandriss81].

The first two enzyme in this pathway, arginase and ornithine aminotransferase, are inducible by L-arginine. pyrroline-5-carboxylate reductase is constitutive, and the last two enzymes ( proline dehydrogenase and Δ1-pyrroline-5-carboxylate dehydrogenase) are inducible by L-proline.

There has also been a report that the cyanobacterium Synechocystis sp. PCC 6803 utilizes the same pathway, catabolizing L-arginine into L-proline, which is eventually converted to L-glutamate [Quintero00]. The authors suggest that the bacteria utilize this pathway as part of the process of conversion of the cyanobacterial storage compound cyanophycin (multi-L-arginyl-poly-L-aspartate) into L-glutamine, a preferred nitrogen source.

Citations: [Overbeek98]

Variants: L-arginine degradation I (arginase pathway), 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 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-ornithine degradation I (L-proline biosynthesis), L-proline biosynthesis I, L-proline biosynthesis II (from arginine), L-proline biosynthesis III, L-proline biosynthesis IV, 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 21-Oct-2005 by Caspi R, SRI International


Brandriss80: Brandriss MC, Magasanik B (1980). "Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae." J Bacteriol 143(3);1403-10. PMID: 6997271

Brandriss81: Brandriss MC, Magasanik B (1981). "Subcellular compartmentation in control of converging pathways for proline and arginine metabolism in Saccharomyces cerevisiae." J Bacteriol 145(3);1359-64. PMID: 7009582

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

Middlehoven64: Middlehoven, W.J. (1964). "The pathway of arginine breakdown in saccharomyces cerevisiae." Biochim Biophys Acta 93;650-2. PMID: 14263163

Overbeek98: Overbeek, R, Larsen, N, Selkov, EE, Maltsev, M "The WIT Database." 1998 WWW URL

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

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

Brandriss92: Brandriss MC, Falvey DA (1992). "Proline biosynthesis in Saccharomyces cerevisiae: analysis of the PRO3 gene, which encodes delta 1-pyrroline-5-carboxylate reductase." J Bacteriol 174(11);3782-8. PMID: 1592829

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.

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

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

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

Degols87: Degols G (1987). "Functional analysis of the regulatory region adjacent to the cargB gene of Saccharomyces cerevisiae. Nucleotide sequence, gene fusion experiments and cis-dominant regulatory mutation analysis." Eur J Biochem 169(1);193-200. PMID: 2824201

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

Deutch01: Deutch CE, Klarstrom JL, Link CL, Ricciardi DL (2001). "Oxidation of L-thiazolidine-4-carboxylate by delta1-pyrroline-5-carboxylate reductase in Escherichia coli." Curr Microbiol 42(6);442-6. PMID: 11381339

Deutch82: Deutch AH, Smith CJ, Rushlow KE, Kretschmer PJ (1982). "Escherichia coli delta 1-pyrroline-5-carboxylate reductase: gene sequence, protein overproduction and purification." Nucleic Acids Res 1982;10(23);7701-14. PMID: 6296787

Eisenstein86: Eisenstein E, Duong LT, Ornberg RL, Osborne JC, Hensley P (1986). "Regulation of arginine metabolism in Saccharomyces cerevisiae. Association of arginase and ornithine transcarbamoylase." J Biol Chem 261(27);12814-9. PMID: 3528164

Fujii02: Fujii T, Mukaihara M, Agematu H, Tsunekawa H (2002). "Biotransformation of L-lysine to L-pipecolic acid catalyzed by L-lysine 6-aminotransferase and pyrroline-5-carboxylate reductase." Biosci Biotechnol Biochem 66(3);622-7. PMID: 12005058

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

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

Green90: Green SM, Eisenstein E, McPhie P, Hensley P (1990). "The purification and characterization of arginase from Saccharomyces cerevisiae." J Biol Chem 265(3);1601-7. PMID: 2404017

Green91: Green SM, Ginsburg A, Lewis MS, Hensley P (1991). "Roles of metal ions in the maintenance of the tertiary and quaternary structure of arginase from Saccharomyces cerevisiae." J Biol Chem 266(32);21474-81. PMID: 1939179

Hill67: Hill DL, Chambers P (1967). "The biosynthesis of proline by Tetrahymena pyriformis." Biochim Biophys Acta 148(2);435-47. PMID: 6075416

Ikemoto89: Ikemoto M, Tabata M, Murachi T, Totani M (1989). "Purification and properties of human erythrocyte arginase." Ann Clin Biochem 26 ( Pt 6);547-53. PMID: 2515788

Ikemoto90: Ikemoto M, Tabata M, Miyake T, Kono T, Mori M, Totani M, Murachi T (1990). "Expression of human liver arginase in Escherichia coli. Purification and properties of the product." Biochem J 270(3);697-703. PMID: 2241902

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
Page generated by Pathway Tools version 20.0 (software by SRI International) on Thu May 5, 2016, BIOCYC13A.