Figure 1.

Energy metabolism in the normal heart and failing heart. In the normal heart, glucose is transported into the cardiomyocyte by GLUT1 or GLUT4. Further, glucose undergoes glycolysis to produce pyruvate, which is transported to the mitochondria by MPC. Transported pyruvate is converted to acetyl CoA by PDH. Fatty acids are transported to the cardiomyocyte by CD36 and FAT. Fatty acids are converted to fatty acid acyl-CoA by ACSL1. The acyl-CoA is transferred to carnitine by CPT1 and transported into mitochondria to undergo fatty acid oxidation producing acetyl-CoA. The acyl-CoA is also used for producing TAG. Dynamic turnover of TAG release fatty acids as a ligand for PPARα. In the failing heart, alterations in glycolysis, glucose oxidation, fatty acid oxidation, TAG dynamics, TCA cycle, and electron transport chain are observed. Uncoupling of glycolysis and glucose oxidation produce by-products for anabolic reaction (i.e., pentose phosphate pathway, aspartate). A black arrow facing upwards indicates an increase and downwards indicates a decrease. ACSL1, Acyl-CoA synthetase long-chain family member 1; ATP, adenosine triphosphate; CPT1, carnitine palmitoyltransferase I; FAT, fatty acid transporter; GLUT, glucose transporter; MPC, mitochondrial pyruvate carrier; PDH, pyruvate dehydrogenase; PPARα: peroxisome proliferator-activated receptor alpha; TCA cycle, tricarboxylic acid cycle; and TAG, triacylglyceride.