Alternate 5-AMP-activated Protein Kinase Kinase*

During myocardial ischemia, activation of 5-AMP-ac-tivated protein kinase (AMPK) leads to the stimulation of glycolysis and fatty acid oxidation. Together these metabolic changes contribute to cardiac dysfunction. Although AMPK signaling in the ischemic heart is well characterized, the relative contribution of phosphoryl-ation by AMPK kinase (AMPKK), and positive alloster-ism by the ratios of AMP:ATP and creatine (Cr):phos-phocreatine (PCr), in stimulating AMPK during ischemia are unknown. In hearts subjected to severe ischemia, the ratios of AMP:ATP and Cr:PCr were sig-nificantly elevated as compared with aerobic hearts. Severe ischemia stimulated AMPK signaling, as demon-strated by an increase in both AMPK activity and acetyl-CoA carboxylase phosphorylation. Although AMP