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PDC deletion: the way to a man’s heart disease

By Mary C. Sugden

Abstract

Copyright © 2008 by the American Physiological Society. 2 The heart has continuous high-energy demands required to sustain efficient contraction. This is met by the metabolism of major circulating substrates (e.g. glucose, lactate or lipids), according to availability, as the heart has a limited capacity for nutrient storage (reviewed 16). Although fatty acid (FA) oxidation rates are invariably higher than glucose oxidation rates, glucose oxidation is more energy efficient that FA oxidation (with approx. 15 % more ATP/O2 molecule). Glucose and lipids compete as oxidative substrates for the heart resulting in either a glucose-FA cycle in which lipid predominates as oxidative substrate, or a reverse glucose-FA cycle, in which lipid oxidation may be suppressed and glucose utilization favoured. In addition, cardiac fuel selection is modified in disease states. Cardiac hypertrophy and heart failure, often characterized by re-expression of fetal genes, can be associated with a preference for glycolytic glucose utilization, whereas the diabetic heart exhibits a major preference for FA as oxidative fuel (reviewed 17). Glucose oxidation is suppressed by phosphorylation (inactivation) of the pyruvate dehydrogenase complex (PDC) by the pyruvate dehydrogenase kinases (PDKs). The heart contains 3 PDK isoforms, PDK1, PDK2 and PDK4. PDK activity in cardiac myocytes is increased in a stable manner in response to increased lipid supply, uptake and utilisation and in response to insulin deficiency (reviewed in 18). PDK upregulation i

Year: 2013
OAI identifier: oai:CiteSeerX.psu:10.1.1.322.6111
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