title: Glycolysis and pyruvate oxidation in cardiac hypertrophy--why so unbalanced?
abstract: Cardiac hypertrophy, induced by chronic pressure or volume overload, is associated with abnormalities in energy metabolism as well as characteristic increases in muscle mass and alterations in the structure of the heart. Hypertrophied hearts display increased rates of glycolysis and overall glucose utilization, but rates of pyruvate oxidation do not rise in step with rates of pyruvate generation. Glycolysis and glucose oxidation, therefore, become markedly less 'coupled' in hypertrophied hearts than in non-hypertrophied hearts. Because the pyruvate dehydrogenase complex (PDC) contributes so powerfully to the control of glucose oxidation, we set out to test the hypothesis that the function of PDC is impaired in cardiac hypertrophy. In this review we describe evidence indicating that the alterations in glucose metabolism in hypertrophied hearts cannot be explained simply by changes in PDC expression or control. Additional mechanisms that may lead to an altered balance of pyruvate metabolism in cardiac hypertrophy are discussed, with commentaries on possible changes in pyruvate transport, NADH shuttles, lactate dehydrogenase, and amino acid metabolism.
authors.affiliation: McDonald Research Laboratories/The iCAPTUR4E Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
authors.forename: H S
authors.initials: HS
authors.lastname: Leong
authors.forename: R W
authors.initials: RW
authors.lastname: Brownsey
authors.forename: J E
authors.initials: JE
authors.lastname: Kulpa
authors.forename: M F
authors.initials: MF
authors.lastname: Allard
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D019289:Pyruvic Acid; D005947:Glucose