title: Overexpression of ornithine aminotransferase: consequences on amino acid homeostasis.
abstract: Ornithine aminotransferase (OAT) is a reversible enzyme expressed mainly in the liver, kidney and intestine. OAT controls the interconversion of ornithine into glutamate semi-aldehyde, and is therefore involved in the metabolism of arginine and glutamine which play a major role in N homeostasis. We hypothesised that OAT could be a limiting step in glutamine-arginine interconversion. To study the contribution of the OAT enzyme in amino acid metabolism, transgenic mice that specifically overexpress human OAT in the liver, kidneys and intestine were generated. The transgene expression was analysed by in situ hybridisation and real-time PCR. Tissue (liver, jejunum and kidney) OAT activity, and plasma and tissue (liver and jejunum) amino acid concentrations were measured. Transgenic male mice exhibited higher OAT activity in the liver (25 (sem 4) v. 11 (sem 1) nmol/min per microg protein for wild-type (WT) mice; P < 0.05) but there were no differences in kinetic parameters (i.e. Km and maximum rate of reaction (Vmax)) between WT and transgenic animals. OAT overexpression decreased plasma and liver ornithine concentrations but did not affect glutamine or arginine homeostasis. There was an inverse relationship between ornithine levels and OAT activity. We conclude that OAT overexpression has only limited metabolic effects, probably due to the reversible nature of the enzyme. Moreover, these metabolic modifications had no effect on phenotype.
authors.affiliation: Laboratoire de Biologie de la Nutrition (EA2498), Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Ventura
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: De Bandt
authors.forename: Frédéric
authors.initials: F
authors.lastname: Segaud
authors.forename: Christine
authors.initials: C
authors.lastname: Perret
authors.forename: Daniel
authors.initials: D
authors.lastname: Robic
authors.forename: Olivier
authors.initials: O
authors.lastname: Levillain
authors.forename: Servane
authors.initials: S
authors.lastname: Le Plenier
authors.forename: Cécile
authors.initials: C
authors.lastname: Godard
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.forename: Christophe
authors.initials: C
authors.lastname: Moinard
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007583:Jejunum / Q000737:chemistry / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009953:Ornithine-Oxo-Acid Transaminase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019076:Transgenes
chemical_list: D000596:Amino Acids; D012333:RNA, Messenger; D009953:Ornithine-Oxo-Acid Transaminase