AJP - Endocrinology and Metabolism, Vol 258, Issue 3 E519-E528, Copyright © 1990 by American Physiological Society

ARTICLES

Pseudoketogenesis in hepatectomized dogs

C. Des Rosiers, J. A. Montgomery, M. Garneau, F. David, O. A. Mamer, P. Daloze, G. Toffolo, C. Cobelli, B. R. Landau and H. Brunengraber
Department of Nutrition, University of Montreal, Quebec, Canada.

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.

This article has been cited by other articles:

				S. Satapati, T. He, T. Inagaki, M. Potthoff, M. E. Merritt, V. Esser, D. J. Mangelsdorf, S. A. Kliewer, J. D. Browning, and S. C. Burgess Partial Resistance to Peroxisome Proliferator-Activated Receptor-{alpha} Agonists in ZDF Rats Is Associated With Defective Hepatic Mitochondrial Metabolism Diabetes, August 1, 2008; 57(8): 2012 - 2021. [Abstract] [Full Text] [PDF]

				B. Comte, G. Vincent, B. Bouchard, M. Jette, S. Cordeau, and C. D. Rosiers A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts J. Biol. Chem., October 17, 1997; 272(42): 26125 - 26131. [Abstract] [Full Text] [PDF]