AMP-activated protein kinase control of energy metabolism in the ischemic heart.
Myocardial ischemia produces an energy-deficient state in heart muscle, which if not corrected can lead to cardiomyocyte death. AMP-activated protein kinase (AMPK) is a key kinase that can increase energy production in the ischemic heart. During ischemia a rapid activation of AMPK occurs, resulting in an activation of both myocardial glucose uptake and glycolysis, as well as an increase in fatty acid oxidation. This activation of AMPK has the potential to increase energy production, thereby protecting the heart during ischemic stress. However, at clinically relevant high levels of fatty acids, ischemia-induced activation of AMPK also stimulates fatty acid oxidation during and following ischemia. This can contribute to ischemic injury secondary to an inhibition of glucose oxidation, which results in a decrease in cardiac efficiency. As a result, AMPK activation has the potential to be either beneficial or harmful in the ischemic heart.
Lopaschuk
G D
GD
Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada. Gary.Lopaschuk@ualberta.ca
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051379:Mice; D017202:Myocardial Ischemia / Q000201:enzymology*; D015425:Myocardial Reperfusion
D005227:Fatty Acids; D008316:Malonyl Coenzyme A; D055372:AMP-Activated Protein Kinases; D005947:Glucose