Integration of ATP Synthesis and ATP Utilization Pathways

Abstract

TAKE HOME MESSAGES • The developing heart is the quintessential example showing changes in the capacity for A TP synthesis and utilization and in their integration. • I n response to acute increases in workload. rapid increases in the rate of ATP synthesis supplies A TP needed for contraction. • I n response to sustained increases in workload. ATP synthesis eventually fails to meet ATP demand. • In the hypertrophied/failing myocardium. many metabolic pathways and isozyme families are remodeled toward a fetal-like pattern. Some proteins increase in proportion to myocyte size while others were relatively diluted and still others increased out of proportion to myocyte size. • Contractile performance decreases in hypoxia and ischemia. and [ATP] falls. Glycolysis increases. but the increase is not sufficient to compensate for the decreases in oxidative phosphorylation (MV02) and in the CK reaction. • AMP-activated protein kinase is a low-fuel sensor that alters substrate selection for A TP synthesis in both acute and chronic low-energy pathophysiologic states. J. S. Ingwall, ATP and the Heart