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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: urea cycle

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: Krebs ornithine cycle, Krebs-Henseleit cycle

Superclasses: Degradation/Utilization/Assimilation Inorganic Nutrients Metabolism Nitrogen Compounds Metabolism

Some taxa known to possess this pathway include ? : Homo sapiens

Expected Taxonomic Range: Bacteria , Eukaryota

Summary:
Most organisms have to deal with the excretion of nitrogen waste originating from protein and amino acid catabolism. In aquatic organisms the most common form of nitrogen waste is ammonia (ammonotelism), while land-dwelling organisms developed ways to convert the toxic ammonia to either urea (ureotelism) or uric acid (uricotelism). Generally, birds and saurian reptiles excrete uric acid, while the remaining species, including mammals, excrete urea [Brown59, Brown59a]. Remarkably, tadpoles excrete ammonia, and shift to urea production during metamorphosis [Brown59a].

The urea is formed in the livers of mammals in a cyclic pathway which was initially named the Krebs-Henseleit cycle after its discoverers, and later became known simply as the urea cycle. This cycle was partially deduced by Krebs & Henseleit in 1932 [Krebs32] and was clarified in the 1940s as the roles of citrulline and argininosuccinate as intermediates were understood [Jackson86].

In this cycle, amino groups donated by ammonia and L-aspartate are converted to urea, while L-ornithine, L-citrulline, L-arginino-succinate, and L-arginine act as intermediates.

Despite the generalization above, the pathway has been documented not only in mammals and amphibians, but in many other organisms as well, including birds [Stockl74], invertebrates [Linton62, Rijavec65], insects [Pant78, Inokuchi69], plants [Reuter61, Kating63], yeast [Chan72], fungi [Prieur71], and even microorganisms [Hiort67, Eckert68].

Superpathways: superpathway of citrulline metabolism

Credits:
Created 28-Sep-2005 by Caspi R , SRI International


References

Brown59: Brown, G.W., Cohen, P.P. (1959). "Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver." J Biol Chem 234(7);1769-74. PMID: 13672961

Brown59a: Brown, G.W., Brown, W.R., Cohen, P.P. (1959). "Comparative biochemistry of urea synthesis. II. Levels of urea cycle enzymes in metamorphosing Rana catesbeiana tadpoles." J Biol Chem 234(7);1775-80. PMID: 13672962

Chan72: Chan PY, Cossins EA (1972). "Regulation of arginase levels by urea and intermediates of the Krebs-Henseleit cycle in Saccharomyces cerevisiae." FEBS Lett 19(4);335-339. PMID: 11946245

Eckert68: Eckert L, Kating H (1968). "[Studies on the metabolism of urea in microorganisms. VII. Dependence of the specific activity of the enzymes of the ornithine cycle and of urease from the duration of culture and the N source]." Arch Mikrobiol 64(2);173-202. PMID: 5709377

Hiort67: Hiort U, Kleczkowski K, Kating H (1967). "[Investigation on the metabolism of urea in microorganisms. VI. Specific activities of the ornithine-cycle enzymes in Micrococcus denitrificans Beij]." Arch Mikrobiol 55(4);311-9. PMID: 5593971

Inokuchi69: Inokuchi T, Horie Y, Ito T (1969). "Urea cycle in the silkworm, BOMBYX MORI." Biochem Biophys Res Commun 35(6);783-7. PMID: 5791517

Jackson86: Jackson MJ, Beaudet AL, O'Brien WE (1986). "Mammalian urea cycle enzymes." Annu Rev Genet 20;431-64. PMID: 3545062

Kating63: Kating, H. (1963). "[Urea synthesis by way of the ornithine cycle in young barley roots.]." Biochem Z 336;489-94. PMID: 13958361

Krebs32: Krebs, H.A., Henseleit, K. (1932). "Untersuchungen uber die Harnstoffbildung im Tierkorper." Hoppe-Seyler's Zeitschrift fur physiologische Chemie 210: 33-46.

Linton62: Linton, S.N., Campbell, J.W. (1962). "Studies on urea cycle enzymes in the terrestrial snail, Otala lactea." Arch Biochem Biophys 97;360-9. PMID: 14465664

Pant78: Pant R, Kumar S (1978). "Is a urea cycle present in insects?." Biochem J 174(1);341-4. PMID: 697760

Prieur71: Prieur P (1971). "[Studies on the metabolism of arginine in Ustilago cynodontis. Demonstration of the enzymes of the urea cycle]." C R Acad Sci Hebd Seances Acad Sci D 272(11);1553-5. PMID: 4996649

Reuter61: Reuter, G. (1961). "Biosynthesis of citrulline in plants." Nature 190;447. PMID: 13741005

Rijavec65: Rijavec M, Kurelec B (1965). "[Urea cycle in some cattle parasites (helminths)]." Z Parasitenkd 26(2);168-72. PMID: 5869779

Stockl74: Stockl W, Dittrich C, Hochman J (1974). "[The course of the urea cycle in the liver of the chicken (author's transl)]." Zentralbl Veterinarmed A 21(10);844-50. PMID: 4217066

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

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

Bhaumik04: Bhaumik P, Koski MK, Bergmann U, Wierenga RK (2004). "Structure determination and refinement at 2.44 A resolution of argininosuccinate lyase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 60(Pt 11);1964-70. PMID: 15502303

Bock83: Bock HG, Su TS, O'Brien WE, Beaudet AL (1983). "Sequence for human argininosuccinate synthetase cDNA." Nucleic Acids Res 11(18);6505-12. PMID: 6194510

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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

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

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

Chen05: 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

Clarke76: Clarke S (1976). "A major polypeptide component of rat liver mitochondria: carbamyl phosphate synthetase." J Biol Chem 251(4);950-61. PMID: 175068

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

Curis05: Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S, Cynober L (2005). "Almost all about citrulline in mammals." Amino Acids NIL. PMID: 16082501

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

Editors93: Editors: Abraham L. Sonenshein, James A. Hoch, Richard Losick (1993). "Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics." American Society For Microbiology, Washington, DC 20005.

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

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

Gotoh97: Gotoh T, Araki M, Mori M (1997). "Chromosomal localization of the human arginase II gene and tissue distribution of its mRNA." Biochem Biophys Res Commun 233(2);487-91. PMID: 9144563

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

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 SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC14A.