Signalling in cardiac metabolism

Abstract

The heart requires large amounts of energy to sustain contractile function, and is the major consumer of energy in the body on a weight basis. Energy reserves are limited in the heart, so energy in the form of adenosine triphosphate (ATP) must be produced continually by the catabolism of different energy carbon substrates. The heart is an ‘omnivore’ and can use a number of different energy substrates, including fatty acids, glucose, lactate, pyruvate, ketones, and amino acids.1–4 Myocardial energy metabolism must be tightly regulated, as the heart cannot afford to produce either too little or too much ATP. In the normal healthy heart, almost all (>95%) of the ATP generated in the heart comes from mitochondrial oxidative phosphorylation, with the remainder being derived from glycolysis.1–4 Of these, fatty acids, glucose, and lactate normally make the greatest contribution to overall energy metabolism, primarily because the heart sees the highest concentration of these energy substrates. Mitochondrial metabolism of fatty acids accounts for ∼60–90% of the total energy production (in the form of ATP), with carbohydrates contributing the remaining 10–40%.3 The contribution of fatty acids and carbohydrates to oxidative ATP production in the heart is influenced by a number of conditions, including alterations in hormonal control, workload, energy substrate supply, and oxygen supply to the heart. The control of these energy-producing pathways is complex, but the different pathways normally work in perfect harmony to ensure the energy needs of the myocardium are met. The energy homeostasis mechanisms of the heart maintain constant ATP production despite periods of dramatic shifts in workload to the heart, and changes in energy substrate and/or oxygen supply to the heart. A complex and integrated cardiac signalling pathway has evolved to allow a precise match between cardiac energy production and usage. This … *Corresponding author. Tel: +1 780 492 2170; fax: +1 780 492 9753. E-mail address: gary.lopaschuk{at}ualberta.ca