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

Enzyme View:

Pathway diagram: L-citrulline degradation

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 DegradationOther Amino Acids Degradation

Some taxa known to possess this pathway include : Aeromonas caviae, Aphanocapsa, Arabidopsis thaliana col, Giardia intestinalis, Halobacterium salinarum, Lactobacillus hilgardii, Lactobacillus plantarum, Mycoplasma hominis, Mycoplasma pneumoniae M129, Oenococcus oeni, Pseudomonas aeruginosa, Spiroplasma citri, Streptococcus ratti, Treponema denticola

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

The citrulline degradation pathway is widely distributed among prokaryotic organisms, often associated with the degradation of arginine into citrulline (see L-arginine degradation V (arginine deiminase pathway)), it has been detected in lactic bacteria [Arena99a, Arena99, Arena05], bacilli [Ottow74, Broman78], Pseudomonas spp. [Vander84, Stalon87], Aeromonas spp. [Stalon82], clostridia [Schmidt52, Mitruka67], Mycoplasma spp. [Schimke66, Tyldesley75, Vander84, Lin86], streptococci [CasianoColon88], Spiroplasma spp. [Igwebe78], Spirochaeta spp. [Blakemore76], halobacteria [Dundas66], and cyanobacteria [Weathers78].

In addition, the pathway is also present in some primitive eukaryotic protozoans, including Trichomonas vaginalis [Linstead83], Tritrichomonas suis [Yarlett94], Hexamita inflata [Biagini03], and Giardia intestinalis, in which it plays a significant role in energy metabolism, providing a route for anaerobic substrate level phosphorylation [Schofield90].

The enzymes of this pathway, as well as arginine deiminase, have also been found in Arabidopsis thaliana col, and it was shown that Arabidopsis chloroplasts can metabolize arginine and citrulline all the way to CO2. However, since Arabidopsis rarely encounters exogenous citrulline, it is thought that in this organism the pathway may serve as a means for extracting nitrogen from endogenous sources [Ludwig93]. The ornithine carbamoyltransferase (OTC) has been identified from a T-DNA-tagged mutant of Arabidopsis and has been shown to be encoded by a gene that overlaps with another, unrelated gene (AUL1), one of the rare cases of gene convergence observed in Arabidopsis thaliana [Quesada99]. Ornithine carbamoyltransferase has also been cloned from other plant sources such as Pisum sativum [Williamson96] and Canavalia lineata [Lee00] [Lee01].

Bacteria that employ this pathway use the enzyme ornithine carbamoyltransferase to convert L-citrulline to L-ornithine and carbamoyl phosphate. The later is then broken into ammonia and CO2 in an ATP-forming reaction, catalyzed by the enzyme carbamate kinase, providing the bacteria with energy, carbon and nitrogen.

While this pathway is a subset of the arginine deiminase pathway, some of the organisms that employ it lack the enzyme arginine deiminase (for example, Oenococcus oeni [Arena05]), and thus are not able to utilize arginine, making this a distinct pathway.

Superpathways: L-arginine degradation V (arginine deiminase pathway), arginine, ornithine and proline interconversion

Unification Links: AraCyc:CITRULLINE-DEG-PWY

Created 20-Sep-1998 by Ying HC, SRI International
Revised 22-Sep-2005 by Caspi R, SRI International
Reviewed 10-Nov-2006 by Foerster H, TAIR


Arena05: Arena ME, Manca de Nadra MC (2005). "Influence of ethanol and low pH on arginine and citrulline metabolism in lactic acid bacteria from wine." Res Microbiol NIL. PMID: 15939575

Arena99: Arena ME, Saguir FM, Manca de Nadra MC (1999). "Arginine, citrulline and ornithine metabolism by lactic acid bacteria from wine." Int J Food Microbiol 52(3);155-61. PMID: 10733246

Arena99a: Arena ME, Saguir FM, Manca de Nadra MC (1999). "Arginine dihydrolase pathway in Lactobacillus plantarum from orange." Int J Food Microbiol 47(3);203-9. PMID: 10359490

Biagini03: Biagini GA, Yarlett N, Ball GE, Billetz AC, Lindmark DG, Martinez MP, Lloyd D, Edwards MR (2003). "Bacterial-like energy metabolism in the amitochondriate protozoon Hexamita inflata." Mol Biochem Parasitol 128(1);11-9. PMID: 12706792

Blakemore76: Blakemore RP, Canale-Parola E (1976). "Arginine catabolism by Treponema denticola." J Bacteriol 128(2);616-22. PMID: 977548

Broman78: Broman K, Lauwers N, Stalon V, Wiame JM (1978). "Oxygen and nitrate in utilization by Bacillus licheniformis of the arginase and arginine deiminase routes of arginine catabolism and other factors affecting their syntheses." J Bacteriol 135(3);920-7. PMID: 690081

CasianoColon88: Casiano-Colon A, Marquis RE (1988). "Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance." Appl Environ Microbiol 54(6);1318-24. PMID: 2843090

Dundas66: Dundas IE, Halvorson HO (1966). "Arginine metabolism in Halobacterium salinarium, an obligately halophilic bacterium." J Bacteriol 91(1);113-9. PMID: 5903088

Igwebe78: Igwebe, E. C. K., Thomas, C. (1978). "Occurrence of enzymes of arginine dihydrolase pathway in Spiroplasma citri." J. Gen. Appl. Microbiol. 84:261-269.

Lee00: Lee Y, Yoo SK, Lee JS, Kwon YM (2000). "Genomic structure of ornithine carbamoyltransferase gene from Canavalia lineata." Mol Cells 10(4);480-5. PMID: 10987149

Lee01: Lee Y, Choi YA, Hwang ID, Kim SG, Kwon YM (2001). "cDNA cloning of two isoforms of ornithine carbamoyltransferase from Canavalia lineata leaves and the effect of site-directed mutagenesis of the carbamoyl phosphate binding site." Plant Mol Biol 46(6);651-60. PMID: 11575720

Lin86: Lin JS (1986). "Arginine deiminase of Mycoplasma hominis: cytoplasmic and membrane-associated forms." J Gen Microbiol 132(6);1467-74. PMID: 3806049

Linstead83: Linstead D, Cranshaw MA (1983). "The pathway of arginine catabolism in the parasitic flagellate Trichomonas vaginalis." Mol Biochem Parasitol 8(3);241-52. PMID: 6312311

Ludwig93: Ludwig RA (1993). "Arabidopsis chloroplasts dissimilate L-arginine and L-citrulline for use as N source." Plant Physiol 101(2);429-34. PMID: 8278506

Mitruka67: Mitruka BM, Costilow RN (1967). "Arginine and ornithine catabolism by Clostridium botulinum." J Bacteriol 93(1);295-301. PMID: 5335895

Ottow74: Ottow JC (1974). "Arginine dihydrolase activity in species of the genus Bacillus revealed by thin-layer chromatography." J Gen Microbiol 84(1);209-13. PMID: 4436643

Quesada99: Quesada V, Ponce MR, Micol JL (1999). "OTC and AUL1, two convergent and overlapping genes in the nuclear genome of Arabidopsis thaliana." FEBS Lett 461(1-2);101-6. PMID: 10561504

Schimke66: Schimke RT, Berlin CM, Sweeney EW, Carroll WR (1966). "The generation of energy by the arginine dihydrolase pathway in Mycoplasma hominis 07." J Biol Chem 241(10);2228-36. PMID: 5911610

Schmidt52: Schmidt, G.C., Logan, M.A., Tytell, A.A. (1952). "The degradation of arginine by Clostridium perfringens (BP6K)." J Biol Chem 198(2);771-83. PMID: 12999794

Schofield90: Schofield PJ, Costello M, Edwards MR, O'Sullivan WJ (1990). "The arginine dihydrolase pathway is present in Giardia intestinalis." Int J Parasitol 20(5);697-9. PMID: 2228433

Stalon82: Stalon V, Simon JP, Mercenier A (1982). "Enzymes of arginine utilization and their formation in Aeromonas formicans NCIB 9232." Arch Microbiol 133(4);295-9. PMID: 6303241

Stalon87: Stalon V, Vander Wauven C, Momin P, Legrain C (1987). "Catabolism of arginine, citrulline and ornithine by Pseudomonas and related bacteria." J Gen Microbiol 133(9);2487-95. PMID: 3129535

Tyldesley75: Tyldesley WR, Kempson SA (1975). "Ultrastructure of the oral epithelium in leukoplakia associated with tylosis and esophageal carcinoma." J Oral Pathol 4(2);49-58. PMID: 126306

Vander84: Vander Wauven C, Pierard A, Kley-Raymann M, Haas D (1984). "Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway." J Bacteriol 160(3);928-34. PMID: 6438064

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

Williamson96: Williamson CL, Lake MR, Slocum RD (1996). "Isolation and characterization of a cDNA encoding a pea ornithine transcarbamoylase (argF) and comparison with other transcarbamoylases." Plant Mol Biol 31(6);1087-92. PMID: 8914525

Yarlett94: Yarlett N, Lindmark DG, Goldberg B, Moharrami MA, Bacchi CJ (1994). "Subcellular localization of the enzymes of the arginine dihydrolase pathway in Trichomonas vaginalis and Tritrichomonas foetus." J Eukaryot Microbiol 41(6);554-9. PMID: 7866382

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

Baur87: Baur H, Stalon V, Falmagne P, Luethi E, Haas D (1987). "Primary and quaternary structure of the catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa. Extensive sequence homology with the anabolic ornithine carbamoyltransferases of Escherichia coli." Eur J Biochem 166(1);111-7. PMID: 3109911

Baur90: Baur H, Tricot C, Stalon V, Haas D (1990). "Converting catabolic ornithine carbamoyltransferase to an anabolic enzyme." J Biol Chem 265(25);14728-31. PMID: 2118516

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

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.

Chen05a: Chen L, Brugger K, Skovgaard M, Redder P, She Q, Torarinsson E, Greve B, Awayez M, Zibat A, Klenk HP, Garrett RA (2005). "The genome of Sulfolobus acidocaldarius, a model organism of the Crenarchaeota." J Bacteriol 187(14);4992-9. PMID: 15995215

Goodyear04: Goodyear CS, Silverman GJ (2004). "Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes." Proc Natl Acad Sci U S A 101(31);11392-7. PMID: 15273292

Hata86: Hata A, Tsuzuki T, Shimada K, Takiguchi M, Mori M, Matsuda I (1986). "Isolation and characterization of the human ornithine transcarbamylase gene: structure of the 5'-end region." J Biochem (Tokyo) 100(3);717-25. PMID: 3782067

Himmelreich96: Himmelreich R, Hilbert H, Plagens H, Pirkl E, Li BC, Herrmann R (1996). "Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae." Nucleic Acids Res 1996;24(22);4420-49. PMID: 8948633

Issaly74: Issaly IM, Issaly AS (1974). "Control of ornithine carbamoyltransferase activityby arginase in Bacillus subtilis." Eur J Biochem 1974;49(3);485-95. PMID: 4216455

Kenklies99: Kenklies J, Ziehn R, Fritsche K, Pich A, Andreesen JR (1999). "Proline biosynthesis from L-ornithine in Clostridium sticklandii: purification of delta1-pyrroline-5-carboxylate reductase, and sequence and expression of the encoding gene, proC." Microbiology 1999;145 ( Pt 4);819-26. PMID: 10220161

Kuo82: Kuo LC, Lipscomb WN, Kantrowitz ER (1982). "Zn(II)-induced cooperativity of Escherichia coli ornithine transcarbamoylase." Proc Natl Acad Sci U S A 1982;79(7);2250-4. PMID: 7048313

Kuo83: Kuo LC "Allosteric cofactor-mediated enzyme cooperativity: A theoretical treatment." Proc Natl Acad Sci USA 1983;80:3243-3247.

Kuo85: Kuo LC, Herzberg W, Lipscomb WN (1985). "Substrate specificity and protonation state of ornithine transcarbamoylase as determined by pH studies." Biochemistry 24(18);4754-61. PMID: 3907689

Kuo88: Kuo LC, Miller AW, Lee S, Kozuma C (1988). "Site-directed mutagenesis of Escherichia coli ornithine transcarbamoylase: role of arginine-57 in substrate binding and catalysis." Biochemistry 1988;27(24);8823-32. PMID: 3072022

Kuo89: Kuo LC, Seaton BA (1989). "X-ray diffraction analysis on single crystals of recombinant Escherichia coli ornithine transcarbamoylase." J Biol Chem 1989;264(27);16246-8. PMID: 2674127

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Legrain72: Legrain C, Halleux P, Stalon V, Glansdorff N (1972). "The dual genetic control of ornithine carbamolytransferase in Escherichia coli. A case of bacterial hybrid enzymes." Eur J Biochem 1972;27(1);93-102. PMID: 4558857

Legrain76: Legrain C, Stalon V (1976). "Ornithine carbamoyltransferase from Escherichia coli W. Purification, structure and steady-state kinetic analysis." Eur J Biochem 1976;63(1);289-301. PMID: 4319

Legrain76a: Legrain C, Stalon V, Glansdorff N (1976). "Escherichia coli ornithine carbamolytransferase isoenzymes: evolutionary significance and the isolation of lambdaargF and lambdaargI transducing bacteriophages." J Bacteriol 1976;128(1);35-8. PMID: 789338

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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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