ornithine oxo acid transaminase


Summary: A pyridoxal phosphate enzyme that catalyzes the formation of glutamate gamma-semialdehyde and an L-amino acid from L-ornithine and a 2-keto-acid. EC

Top Publications

  1. Cleary M, Dorland L, de Koning T, Poll The B, Duran M, Mandell R, et al. Ornithine aminotransferase deficiency: diagnostic difficulties in neonatal presentation. J Inherit Metab Dis. 2005;28:673-9 pubmed
    ..Enzyme and mutation studies confirmed the diagnosis. OAT deficiency should be included in differential diagnosis of neonatal hyperammonaemia. ..
  2. Strizhov N, Abraham E, Okrész L, Blickling S, Zilberstein A, Schell J, et al. Differential expression of two P5CS genes controlling proline accumulation during salt-stress requires ABA and is regulated by ABA1, ABI1 and AXR2 in Arabidopsis. Plant J. 1997;12:557-69 pubmed
  3. Dekaney C, Wu G, Jaeger L. Ornithine aminotransferase messenger RNA expression and enzymatic activity in fetal porcine intestine. Pediatr Res. 2001;50:104-9 pubmed
    ..This capability may be important for synthesis of arginine, proline, ornithine, and polyamines for development and metabolic activity of the intestine during gestation or for somatic growth of the fetus. ..
  4. Roosens N, Thu T, Iskandar H, Jacobs M. Isolation of the ornithine-delta-aminotransferase cDNA and effect of salt stress on its expression in Arabidopsis thaliana. Plant Physiol. 1998;117:263-71 pubmed
    ..Delta1-pyrroline-5-carboxylate synthase mRNA was still induced at a similar level. Therefore, for the adult plants the free Pro increase seemed to be due to the activity of the enzymes of the glutamate pathway. ..
  5. Sekhar P, Amrutha R, Sangam S, Verma D, Kishor P. Biochemical characterization, homology modeling and docking studies of ornithine delta-aminotransferase--an important enzyme in proline biosynthesis of plants. J Mol Graph Model. 2007;26:709-19 pubmed
    ..These observations are in conformity with the results obtained from experimental investigations. ..
  6. Wu G, Jaeger L, Bazer F, Rhoads J. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem. 2004;15:442-51 pubmed
    ..This new knowledge will be beneficial for designing the next generation of enteral and parenteral amino acid solutions to optimize nutrition and health in this compromised population...
  7. Wang T, Lawler A, Steel G, Sipila I, Milam A, Valle D. Mice lacking ornithine-delta-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration. Nat Genet. 1995;11:185-90 pubmed
    ..Over several months, OAT-deficient mice develop a retinal degeneration with involvement of photoreceptors and pigment epithelium. OAT-deficient mice appear to be an excellent model of human GA. ..
  8. Venta P, Cao Y, Dittmer N, Scott Emuakpor J. A PCR-RSP Csp6I site in the canine ornithine aminotransferase (OAT) gene. Anim Genet. 1998;29:325-6 pubmed
  9. Dhanakoti S, Brosnan M, Herzberg G, Brosnan J. Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney. Biochem J. 1992;282 ( Pt 2):369-75 pubmed
    ..Subcellular fractionation of kidney cortex revealed that argininosuccinate synthase and lyase are cytosolic. We therefore conclude that arginine synthesis occurs in the cytoplasm of the cells of the proximal convoluted tubule. ..

More Information


  1. Jensen T, Sullivan D, Morgan R, Taichman L, Nussenblatt R, Blaese R, et al. Retrovirus-mediated gene transfer of ornithine-delta-aminotransferase into keratinocytes from gyrate atrophy patients. Hum Gene Ther. 1997;8:2125-32 pubmed
    ..Ornithine catabolism was maintained at high levels when the transduced patient keratinocytes were differentiated in vitro as a multilayered cutaneous organoid...
  2. Seiler N. Ornithine aminotransferase, a potential target for the treatment of hyperammonemias. Curr Drug Targets. 2000;1:119-53 pubmed
    ..The confirmation of this and related observations in higher species will show, whether OAT inactivation has potentials in the treatment of hyperammonemic states. ..
  3. Ishikawa H, Matsuzawa T, Ohashi K, Nagamura Y. A novel method for measuring serum ornithine carbamoyltransferase. Ann Clin Biochem. 2003;40:264-8 pubmed
    ..Here we report a new method for serum ornithine carbamoyl-transferase assay which might be useful for clinical diagnosis of hepatic disorders, including hepatic cancer. ..
  4. Santos L, Fiona W, Walter J. Dietary compliance in ornithine aminotransferase deficiency. J Inherit Metab Dis. 2006;29:240 pubmed
    ..For the older patients, alternative treatments such as the use of oral lysine to increase renal losses of ornithine need to be investigated further (Peltola et al 2000). ..
  5. O Donnell J, Vannas Sulonen K, Shows T, Cox D. Gyrate atrophy of the choroid and retina: assignment of the ornithine aminotransferase structural gene to human chromosome 10 and mouse chromosome 7. Am J Hum Genet. 1988;43:922-8 pubmed
    ..Our findings, combined with recent molecular studies, indicate that human OAT probes specific for chromosome 10 will be useful for the diagnosis and genetic counseling of individuals at risk for gyrate atrophy...
  6. Wang G, Shang L, Burgett A, Harran P, Wang X. Diazonamide toxins reveal an unexpected function for ornithine delta-amino transferase in mitotic cell division. Proc Natl Acad Sci U S A. 2007;104:2068-73 pubmed
    ..Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development. ..
  7. Inana G, Chambers C, Hotta Y, Inouye L, Filpula D, Pulford S, et al. Point mutation affecting processing of the ornithine aminotransferase precursor protein in gyrate atrophy. J Biol Chem. 1989;264:17432-6 pubmed
  8. Kaneko S, Okuda Ashitaka E, Ando A, Nishimura K, Igarashi K, Maeda M, et al. Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells. Am J Physiol Cell Physiol. 2007;293:C729-37 pubmed
    ..These results suggest that spermine plays an important role in stimulation of mRNA expression of CAT-1, which is a crucial role in ornithine cytotoxicity in OAT-deficient hTERT-RPE cells. ..
  9. Keller J, Baurick K, Rutt G, O Malley M, Sonafrank N, Reynolds R, et al. Pseudomonas cepacia 2,2-dialkylglycine decarboxylase. Sequence and expression in Escherichia coli of structural and repressor genes. J Biol Chem. 1990;265:5531-9 pubmed
    ..Expression is induced by S-isovaline, 2-methylalanine, and D-2-aminobutanoic acid, but not by glycine, D- or L-alanine, L-2-aminobutanoic acid, R-isovaline, or other alkyl amino acids...
  10. Kaneko S, Ando A, Okuda Ashitaka E, Maeda M, Furuta K, Suzuki M, et al. Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007;48:464-71 pubmed
    ..The results suggest that ornithine transport via CAT-1 may play a crucial role in ornithine cytotoxicity in hTERT-RPE cells. Reduction of the ornithine transport via CAT-1 may be a new target for treatment of gyrate atrophy. ..
  11. Deignan J, Livesay J, Shantz L, Pegg A, O Brien W, Iyer R, et al. Polyamine homeostasis in arginase knockout mice. Am J Physiol Cell Physiol. 2007;293:C1296-301 pubmed
    ..These results suggest that endogenous arginase-derived ornithine may not directly contribute to polyamine homeostasis in mice. Alternate sources such as diet may provide sufficient polyamines for maintenance in mammalian tissues. ..
  12. Funck D, Stadelhofer B, Koch W. Ornithine-delta-aminotransferase is essential for arginine catabolism but not for proline biosynthesis. BMC Plant Biol. 2008;8:40 pubmed publisher
    ..Pro biosynthesis occurs predominantly or exclusively via the Glu pathway in Arabidopsis and does not depend on Glu produced by Arg and Orn catabolism. ..
  13. Remacle C, Cline S, Boutaffala L, Gabilly S, Larosa V, Barbieri M, et al. The ARG9 gene encodes the plastid-resident N-acetyl ornithine aminotransferase in the green alga Chlamydomonas reinhardtii. Eukaryot Cell. 2009;8:1460-3 pubmed publisher
    ..Integration of an engineered ARG9 cassette in the plastid chromosome of the nuclear arg9 mutant restores arginine prototrophy. This suggests that ARG9 could be used as a new selectable marker for plastid transformation. ..
  14. Stránská J, Tylichova M, Kopecny D, Snégaroff J, Sebela M. Biochemical characterization of pea ornithine-delta-aminotransferase: substrate specificity and inhibition by di- and polyamines. Biochimie. 2010;92:940-8 pubmed publisher
    ..On the other hand, putrescine, spermidine and others represented weak non-competitive inhibitors. A model of the molecular structure of PsOAT was obtained using the crystal structure of human OAT as a template. ..
  15. Gachomo E, Allen J, Pfeffer P, Govindarajulu M, Douds D, Jin H, et al. Germinating spores of Glomus intraradices can use internal and exogenous nitrogen sources for de novo biosynthesis of amino acids. New Phytol. 2009;184:399-411 pubmed publisher
    ..Germinating spores can make effective use of different N sources and the ability to synthesize amino acids does not limit presymbiotic growth of arbuscular mycorrhizal (AM) spores. ..
  16. Shull J, Pennington K, Pitot H, Boryca V, Schulte B. Isolation and characterization of the rat gene encoding ornithine aminotransferase. Biochim Biophys Acta. 1992;1132:214-8 pubmed
    ..Isolation of rOAT provides an important tool for examining the molecular mechanisms through which estrogen and thyroid hormone regulate transcription of this gene in a cell-type specific manner. ..
  17. Tadros S, D Souza M, Zettel M, Zhu X, Waxmonsky N, Frisina R. Glutamate-related gene expression changes with age in the mouse auditory midbrain. Brain Res. 2007;1127:1-9 pubmed
    ..The up-regulation of Slc1a3 gene expression may reflect a cellular compensatory mechanism to protect against age-related glutamate or calcium excitoxicity. ..
  18. Mueckler M, Pitot H. Sequence of the precursor to rat ornithine aminotransferase deduced from a cDNA clone. J Biol Chem. 1985;260:12993-7 pubmed
    ..Homology was also observed between residues 286 through 362 ornithine aminotransferase precursor and a region containing the pyridoxyl phosphate binding domain of mitochondrial aspartate aminotransferase. ..
  19. Shull J, Esumi N, Colwell A, Pennington K, Jendoubi M. Sequence of the promoter region of the mouse gene encoding ornithine aminotransferase. Gene. 1995;162:275-7 pubmed
    ..This region contains sequence motifs resembling binding sites for general transcription factors, as well as other trans-acting regulatory proteins. ..
  20. Cadoret A, Ovejero C, Terris B, Souil E, Levy L, Lamers W, et al. New targets of beta-catenin signaling in the liver are involved in the glutamine metabolism. Oncogene. 2002;21:8293-301 pubmed
    ..Because a linkage of the glutamine pathway to hepatocarcinogenesis has already been demonstrated, we propose that regulation of these three genes of glutamine metabolism by beta-catenin is a contributing factor to liver carcinogenesis. ..
  21. Ramesh V, Cheng S, Kozak C, Herron B, Shih V, Taylor B, et al. Mapping of ornithine aminotransferase gene sequences to mouse chromosomes 7, X, and 3. Mamm Genome. 1992;3:17-22 pubmed
    ..Progeny of an intersubspecific backcross were used to map the Chr 7 locus between Tyr and Int-2, near Cyp2e-1. ..
  22. Cañas R, Villalobos D, Díaz Moreno S, Canovas F, Cantón F. Molecular and functional analyses support a role of Ornithine-{delta}-aminotransferase in the provision of glutamate for glutamine biosynthesis during pine germination. Plant Physiol. 2008;148:77-88 pubmed publisher
    ..Taken together, our data support that delta-OAT plays an important role in this process providing glutamate for glutamine biosynthesis during early pine growth. ..
  23. Mashima Y, Murakami A, Weleber R, Kennaway N, Clarke L, Shiono T, et al. Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. Am J Hum Genet. 1992;51:81-91 pubmed
    ..Thus, the mRNA level can be reduced by nonsense-codon mutations, but the position of the mutation may be important, with earlier premature-translation termination having a greater effect than a later mutation. ..
  24. Mohamed S, Mohamed T, Fahmy A, El Badry M, Abdel Gany S. Fasciola gigantica: enzymes of the ornithine-proline-glutamate pathway--characterization of delta1-pyrroline-5-carboxylate dehydrogenase. Exp Parasitol. 2008;118:47-53 pubmed
    ..While 3mM AMP caused 31% activation of enzyme, 3mM ADP and ATP inhibited activity by 18% and 23%, respectively. Apart from Cu2+, the divalent cations that were studied caused partial inhibitory effects on the enzyme. ..
  25. Lafreniere R, Geraghty M, Valle D, Shows T, Willard H. Ornithine aminotransferase-related sequences map to two nonadjacent intervals on the human X chromosome short arm. Genomics. 1991;10:276-9 pubmed
    ..3-p11.23. These results should help guide long-range cloning and mapping studies, as well as refine the genetic linkage map in this region of the X chromosome. ..
  26. Kaufman D, Ramesh V, McClatchey A, Menkes J, Tobin A. Detection of point mutations associated with genetic diseases by an exon scanning technique. Genomics. 1990;8:656-63 pubmed
  27. Shen B, Ramesh V, Mueller R, Hohenester E, Hennig M, Jansonius J. Crystallization and preliminary X-ray diffraction studies of recombinant human ornithine aminotransferase. J Mol Biol. 1994;243:128-30 pubmed
    ..A complete native data set to 2.3 A resolution was collected using synchrotron radiation. ..
  28. Wang T, Steel G, Milam A, Valle D. Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina. Proc Natl Acad Sci U S A. 2000;97:1224-9 pubmed
    ..This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA. ..
  29. Razavizadeh R, Ehsanpour A, Ahsan N, Komatsu S. Proteome analysis of tobacco leaves under salt stress. Peptides. 2009;30:1651-9 pubmed publisher
    ..Thus, down-regulation of the stromal 70-kDa heat shock protein in response to salt stress is likely the cause of failure to protect cells against salt stress of tobacco plants. ..
  30. Daune Anglard G, Bonaventure N, Seiler N. Some biochemical and pathophysiological aspects of long-term elevation of brain ornithine concentrations. Pharmacol Toxicol. 1993;73:29-34 pubmed
    ..This residual activity may be sufficient to maintain vital functions. ..
  31. Haslett M, Pink D, Walters B, Brosnan M. Assay and subcellular localization of pyrroline-5-carboxylate dehydrogenase in rat liver. Biochim Biophys Acta. 2004;1675:81-6 pubmed
    ..Thus, it can be concluded that P5CDh occurs only in mitochondria, not in both mitochondria and cytoplasm, as had previously been reported. ..
  32. Ruijter J, Gieling R, Markman M, Hagoort J, Lamers W. Stereological measurement of porto-central gradients in gene expression in mouse liver. Hepatology. 2004;39:343-52 pubmed
    ..The method can be applied to any tissue component that can be stained quantitatively. ..
  33. Empel J, Sitkiewicz I, Andrukiewicz A, Lasocki K, Borsuk P, Weglenski P. arcA, the regulatory gene for the arginine catabolic pathway in Aspergillus nidulans. Mol Genet Genomics. 2001;266:591-7 pubmed
    ..Two mutations in arcA, one gain-of-function and one loss-of-function, have been sequenced and the effects of these mutations on the expression of the agaA gene at the transcriptional level are reported. ..
  34. Rao G, Cotlier E. Ornithine delta-aminotransferase activity in retina and other tissues. Neurochem Res. 1984;9:555-62 pubmed
    ..Arginine glycine transamidinase activity was not detectable in human retina, thus a previously postulated creatine phosphate deprivation in OAT deficiency may not be applicable to the pathogenesis of the disease. ..
  35. Natesan S, Reddy S. Compensatory changes in enzymes of arginine metabolism during renal hypertrophy in mice. Comp Biochem Physiol B Biochem Mol Biol. 2001;130:585-95 pubmed
    ..The results suggest that compensation in OAT activity to chronic reduction in renal mass was complete, but only partial in the case of other enzymes. ..
  36. Inana G, Totsuka S, Redmond M, Dougherty T, Nagle J, Shiono T, et al. Molecular cloning of human ornithine aminotransferase mRNA. Proc Natl Acad Sci U S A. 1986;83:1203-7 pubmed
    ..2 kilobases. The level of OATase mRNA in the normal human retina is approximately equal to 1/100th the level of rhodopsin mRNA and 1/5th to 1/10th the level present in the retinoblastoma cells. ..
  37. Shull J, Pitot H. The ornithine aminotransferase gene in gyrate atrophy of the retina: analysis of expression and gross structure of this gene in cultured fibroblasts. In Vitro Cell Dev Biol. 1989;25:971-6 pubmed
    ..This study indicates that the lack of OAT enzyme activity associated with GA is the result of a variety of different molecular defects within the OAT gene...
  38. Storici P, Capitani G, Muller R, Schirmer T, Jansonius J. Crystal structure of human ornithine aminotransferase complexed with the highly specific and potent inhibitor 5-fluoromethylornithine. J Mol Biol. 1999;285:297-309 pubmed
    ..This requires a different side-chain conformation of Glu235. Lys292 is the only obvious candidate for catalyzing the rate-limiting proton transfer steps in the transamination reaction. ..
  39. Valtonen M, Näntö Salonen K, Jääskeläinen S, Heinänen K, Alanen A, Heinonen O, et al. Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia. J Inherit Metab Dis. 1999;22:855-66 pubmed
    ..Early degenerative and atrophic brain changes and abnormal EEG are thus features of GA, in addition to the well-characterized eye and muscle manifestations...
  40. Kim D, Shibato J, Agrawal G, Fujihara S, Iwahashi H, Kim D, et al. Gene transcription in the leaves of rice undergoing salt-induced morphological changes (Oryza sativa L.). Mol Cells. 2007;24:45-59 pubmed
    ..These results provide new insight into the effect of salt stress on the expression of genes related to antioxidant enzymes, proline and GABA as well as of genes in several functional categories. ..
  41. Mashima Y, Shiono T, Tamai M, Inana G. Heterogeneity and uniqueness of ornithine aminotransferase mutations found in Japanese gyrate atrophy patients. Curr Eye Res. 1996;15:792-6 pubmed
  42. Roschinger W, Endres W, Shin Y. Characteristics of L-ornithine: 2-oxoacid aminotransferase and potential prenatal diagnosis of gyrate atrophy of the choroid and retina by first trimester chorionic villus sampling. Clin Chim Acta. 2000;296:91-100 pubmed
    ..In addition we have found the enzyme expressed in native and cultured chorionic villi indicating a potential detection of the disease during the first trimester of pregnancy...
  43. Dzikowska A, Swianiewicz M, Talarczyk A, Wisniewska M, Goras M, Scazzocchio C, et al. Cloning, characterisation and regulation of the ornithine transaminase (otaA) gene of Aspergillus nidulans. Curr Genet. 1999;35:118-26 pubmed
    ..AREA binding-sites are composed of GATT sequences which are not typical binding sites for the GATA - binding family of transcription factors. ..
  44. Mumenthaler S, Yu H, Tze S, Cederbaum S, Pegg A, Seligson D, et al. Expression of arginase II in prostate cancer. Int J Oncol. 2008;32:357-65 pubmed
    ..More specifically, the elevated AII expression seen in androgen-dependent and in more differentiated prostate cancers suggests that AII could be a potentially useful marker of early stage prostate adenocarcinoma. ..
  45. Mattioli R, Marchese D, D Angeli S, Altamura M, Costantino P, Trovato M. Modulation of intracellular proline levels affects flowering time and inflorescence architecture in Arabidopsis. Plant Mol Biol. 2008;66:277-88 pubmed
    ..Salt-stress restored expression of P5CS1 and proline accumulation in P5CS1-transformed plants, as well as rescuing growth. Our data suggest that proline plays a key role in flower transition, bolting and coflorescence formation. ..
  46. Threadgill D, Womack J. Mapping HSA10 homologous loci in cattle. Cytogenet Cell Genet. 1991;57:123-6 pubmed
    ..VIM and IL2R mapped to U11; ADRA2 and OAT mapped to U26; and RBP3, PLAU, and HK1 mapped to U28. ..
  47. Dzikowska A, Kacprzak M, Tomecki R, Koper M, Scazzocchio C, Weglenski P. Specific induction and carbon/nitrogen repression of arginine catabolism gene of Aspergillus nidulans--functional in vivo analysis of the otaA promoter. Fungal Genet Biol. 2003;38:175-86 pubmed
    ..This suppression can be achieved neither by growing of the proline auxotroph under carbon/nitrogen derepressing conditions nor by introducing of a creA(d) mutation. ..
  48. Yu H, Yoo P, Aguirre C, Tsoa R, Kern R, Grody W, et al. Widespread expression of arginase I in mouse tissues. Biochemical and physiological implications. J Histochem Cytochem. 2003;51:1151-60 pubmed
  49. Seiler N, Grauffel C, Daune Anglard G, Sarhan S, Knodgen B. Decreased hyperammonaemia and orotic aciduria due to inactivation of ornithine aminotransferase in mice with a hereditary abnormal ornithine carbamoyltransferase. J Inherit Metab Dis. 1994;17:691-703 pubmed
  50. Hu C, Khalil S, Zhaorigetu S, Liu Z, Tyler M, Wan G, et al. Human Delta1-pyrroline-5-carboxylate synthase: function and regulation. Amino Acids. 2008;35:665-72 pubmed publisher
    ..It would be of importance to further investigate the role of P5CS as a p53 downstream effector and how P5CS.short expression is regulated by hormones and factors of alternative splicing in cells isolated from model animals. ..
  51. Turchetto Zolet A, Margis Pinheiro M, Margis R. The evolution of pyrroline-5-carboxylate synthase in plants: a key enzyme in proline synthesis. Mol Genet Genomics. 2009;281:87-97 pubmed publisher
    ..Despite the high number of conserved residues in plant P5CS sequences, positive selection was observed at different regions of P5CS paralogous genes and also when dicots and monocots were contrasted. ..
  52. Xue X, Liu A, Hua X. Proline accumulation and transcriptional regulation of proline biosynthesis and degradation in Brassica napus. BMB Rep. 2009;42:28-34 pubmed
    ..During development, proline content was high in reproductive organs and was accompanied by markedly high expression of BnP5CS and BnPDH, suggesting possible roles of proline during flower development. [BMB reports 2009; 42(1): 28-34]. ..
  53. Peltola K, Näntö Salonen K, Heinonen O, Jääskeläinen S, Heinänen K, Simell O, et al. Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase. Ophthalmology. 2001;108:721-9 pubmed
    ..The group was made up of homozygotes and compound heterozygotes for mutation L402P in the ornithine aminotransferase (OAT) gene...