title: Pseudoketogenesis in hepatectomized dogs.
abstract: Overestimation of ketone body turnover in vivo, measured by tracer kinetics, could occur if specific activity or molar percent enrichment is diluted in extrahepatic tissues by label exchange via reversal of 3-oxoacid-CoA transferase, a process we call pseudoketogenesis. To test this hypothesis, euglycemic hepatectomized dogs were injected with a bolus of acetoacetate (0.8 mmol/kg), 32% enriched in [3,4-13C2]acetoacetate. Concentrations and labeling patterns of blood acetoacetate and R-3-hydroxybutyrate were measured by selected ion-monitoring gas chromatography-mass spectrometry. During the 60 min after bolus injection of [3,4-13C2]acetoacetate, the molar percent enrichment of blood [3,4-13C2]acetoacetate decreased to 73 +/- 3% (n = 5) in controls and to 11.5 +/- 0.8% (n = 3) during infusion of dichloroacetate, an activator of pyruvate dehydrogenase. The enrichment of R-3-hydroxy-[3,4-13C2]butyrate followed closely that of [3,4-13C2]acetoacetate. These dilutions occurred despite a net uptake of ketone bodies. Concomitantly, 10.6 +/- 2.2 (n = 5) and 6.0 +/- 2.9% (n = 3) of [13C]acetoacetate molecules were labeled on all four carbons in control and dichloroacetate-treated dogs, respectively. This uniformly labeled acetoacetate arises from partial equilibration between [3,4-13C2]acetoacetate and [1,2-13C2]acetyl-CoA via the reactions catalyzed by 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. Our data demonstrate the reversibility of the 3-oxoacid-CoA transferase in intact extrahepatic tissues and support the concept of pseudoketogenesis. This phenomenon has been quantitated by kinetic analysis of the data.
authors.affiliation: Department of Nutrition, University of Montreal, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Des Rosiers
authors.forename: J A
authors.initials: JA
authors.lastname: Montgomery
authors.forename: M
authors.initials: M
authors.lastname: Garneau
authors.forename: F
authors.initials: F
authors.lastname: David
authors.forename: O A
authors.initials: OA
authors.lastname: Mamer
authors.forename: P
authors.initials: P
authors.lastname: Daloze
authors.forename: G
authors.initials: G
authors.lastname: Toffolo
authors.forename: C
authors.initials: C
authors.lastname: Cobelli
authors.forename: B R
authors.initials: BR
authors.lastname: Landau
authors.forename: H
authors.initials: H
authors.lastname: Brunengraber
mesh_terms: D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D004285:Dogs; D006498:Hepatectomy; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological
chemical_list: D000090:Acetoacetates; D002247:Carbon Isotopes; D006885:Hydroxybutyrates; D007657:Ketone Bodies; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid