Metabolic adaptation of the hypertrophied heart: role of the malate/aspartate and alpha-glycerophosphate shuttles.

Activation of the malate/aspartate and alpha -glycerophosphate shuttles (the NADH shuttles) has been identified in glycolytically active newborn myocardium. The goal of this study was to determine if the NADH shuttles and their regulatory genes are activated in hypertrophied myocardium as substrate utilization shifts away from fatty acids and toward glucose and lactate. Capacity of the shuttles was determined in cardiac mitochondria isolated one week, one month, and three months following aortic banding or sham operation. Myocardial steady-state mRNA and protein levels of regulatory enzymes were also measured. Despite a significant increase in left ventricular mass and activation of the atrial natriuretic peptide gene, no change in malate/aspartate nor alpha -glycerophosphate shuttle capacity was found at any of the three time points studied. Reactivation of the genes encoding the regulatory inner mitochondrial membrane proteins was not found in the hypertrophied myocardium, though these genes were down regulated one week following aortic-banding. These results suggest that sufficient malate/aspartate and alpha -glycerophosphate shuttle capacity exists in cardiac mitochondria to accommodate increased shuttle flux as hypertrophied myocardium becomes more glycolytically active. Copyright 2000 Academic Press.