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MetaCyc Pathway: L-ornithine biosynthesis II
Inferred from experiment

Pathway diagram: L-ornithine biosynthesis II

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: BiosynthesisAmino Acids BiosynthesisOther Amino Acid BiosynthesisL-Ornithine Biosynthesis

Some taxa known to possess this pathway include : Homo sapiens

Expected Taxonomic Range: Metazoa

General Background

L-ornithine is an amino acid, but it is not a component of proteins nor is it coded for by DNA. In mammals, it plays a role in the urea cycle for the disposal of ammonia where it is synthesized from L-arginine by arginase 1. It is also a precursor of L-arginine synthesis in the urea cycle and L-citrulline-nitric oxide cycle.

The initial steps of ornithine biosynthesis in lower organisms proceeds either via N acetylated intermediates or the use of a dedicated carrier protein to protect the intermediates. This is presumed to prevent the spontaneous cyclization of glutamate derivatives, which leads to proline biosynthesis [Caldovic03]. Indeed in mammals, L-glutamate-5-semialdehyde can spontaneously cyclize to (S)-1-pyrroline-5-carboxylate, an intermediate in L-proline biosynthesis I. In lower organisms that lack the L-citrulline-nitric oxide cycle and urea cycle, ornithine participates in the de novo biosynthesis of L-arginine.

About this Pathway

This pathway describes the de novo biosynthesis of L-ornithine from 2-oxoglutarate which occurs in the mitochondria. L-glutamate is formed from 2-oxoglutarate within the mitochondrial matrix by the mitochondrial glutamate dehydrogenases [Shashidharan94]. L-glutamate is then converted to L-glutamate-5-semialdehyde by mitochondrial δ-1-pyrroline-5-carboxylate synthase [Aral96].

The conversion of L-glutamate-5-semialdehyde to L-ornithine occurs within the mitochondrial lumen by ornithine aminotransferase [Kobayashi89]. At this point, L-ornithine can enter either L-citrulline-nitric oxide cycle or urea cycle to synthesize L-arginine.

Variants: L-Nδ-acetylornithine biosynthesis, L-ornithine biosynthesis I

Revised 23-Oct-2013 by Weerasinghe D, SRI International


Aral96: Aral B, Schlenzig JS, Liu G, Kamoun P (1996). "Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis." C R Acad Sci III 319(3);171-8. PMID: 8761662

Caldovic03: Caldovic L, Tuchman M (2003). "N-acetylglutamate and its changing role through evolution." Biochem J 372(Pt 2);279-90. PMID: 12633501

Kobayashi89: Kobayashi T, Nishii M, Takagi Y, Titani K, Matsuzawa T (1989). "Molecular cloning and nucleotide sequence analysis of mRNA for human kidney ornithine aminotransferase. An examination of ornithine aminotransferase isozymes between liver and kidney." FEBS Lett 255(2);300-4. PMID: 2507357

Shashidharan94: Shashidharan P, Michaelidis TM, Robakis NK, Kresovali A, Papamatheakis J, Plaitakis A (1994). "Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene." J Biol Chem 269(24);16971-6. PMID: 8207021

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

Baich69: Baich A (1969). "Proline synthesis in Escherichia coli. A proline-inhibitable glutamic acid kinase." Biochim Biophys Acta 1969;192(3);462-7. PMID: 4904678

Baich71: Baich A (1971). "The biosynthesis of proline in Escherichia coli: phosphate-dependent glutamate -semialdehyde dehydrogenase (NADP), the second enzyme in the pathway." Biochim Biophys Acta 244(1);129-34. PMID: 4399189

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

Baumgartner00: Baumgartner MR, Hu CA, Almashanu S, Steel G, Obie C, Aral B, Rabier D, Kamoun P, Saudubray JM, Valle D (2000). "Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase." Hum Mol Genet 9(19);2853-8. PMID: 11092761

Baumgartner05: Baumgartner MR, Rabier D, Nassogne MC, Dufier JL, Padovani JP, Kamoun P, Valle D, Saudubray JM (2005). "Delta1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline." Eur J Pediatr 164(1);31-6. PMID: 15517380

Bicknell08: Bicknell LS, Pitt J, Aftimos S, Ramadas R, Maw MA, Robertson SP (2008). "A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome." Eur J Hum Genet 16(10);1176-86. PMID: 18478038

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.

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

Csonka88: Csonka LN, Gelvin SB, Goodner BW, Orser CS, Siemieniak D, Slightom JL (1988). "Nucleotide sequence of a mutation in the proB gene of Escherichia coli that confers proline overproduction and enhanced tolerance to osmotic stress." Gene 1988;64(2);199-205. PMID: 2841193

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

Fang02: Fang J, Hsu BY, MacMullen CM, Poncz M, Smith TJ, Stanley CA (2002). "Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutations." Biochem J 363(Pt 1);81-7. PMID: 11903050

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

Hayzer81: Hayzer DJ, Leisinger T (1981). "Proline biosynthesis in Escherichia coli. Stoichiometry and end-product identification of the reaction catalysed by glutamate semialdehyde dehydrogenase." Biochem J 197(2);269-74. PMID: 7034716

Hayzer82: Hayzer DJ, Leisinger T (1982). "Proline biosynthesis in Escherichia coli. Purification and characterisation of glutamate-semialdehyde dehydrogenase." Eur J Biochem 1982;121(3);561-5. PMID: 7035170

Hayzer83: Hayzer DJ, Leisinger T (1983). "Proline biosynthesis in Escherichia coli. Kinetic and mechanistic properties of glutamate semialdehyde dehydrogenase." Biochim Biophys Acta 742(2);391-8. PMID: 6337636

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

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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
Page generated by Pathway Tools version 19.5 (software by SRI International) on Tue May 3, 2016, biocyc13.