Fig. 16.46 •Fig. 16.46 Overall Scheme for Production and Utilization of Adenosine Triphosphate (ATP) Within a Cardiac Myocyte. Pathwaysforutilizationofglucose,fattyacids(FA),andlactateareindicated,asaretherequirementsforO2andH+bytheelectrontransportchaininmitochondria.ADP,adenosinediphosphate;CoA,coenzymeA;CPT-I,carnitinepalmitoyltransferase;G-6-P,glucose-6-phosphate;GLUT,glucosetransporter;NADH,nicotinamideadenosinedehydrogenase;PDH,pyruvatedehydrogenase;Pi,inorganicphosphate;SR,sarcoplasmicreticulum;TG,triglyceride.ATPase FACPT-I Cardiomyocyte Citric Acid CycleCO2 Acetyl-CoA Acetyl-CoA NADH NADH Lactate GLUT Glycogen Cytosol Contractile work, SR Ca++ uptake, lon homeostasis G-6-P PDH Pyruvate Electron Transport Chain TGATP ATP ATP ADP + Pi ADP + Pi ADP + Pi H+ O2 Mitochondrion — GLYCOLYSIS Fatty Acid ˛-Oxidation
The healthy heart has a relatively constant level of ATP (≈5µmol/g wet weight) despite an extremely high rate of ATP hydrolysis (≈0.3µmol/g−1/second−1). The tissue content of ATP is low in relation to the rate of breakdown and production; complete turnover of the myocardial ATP content occurs approximately every 12 seconds in the heart at rest. ATP hydrolysis (see
Fig. 16.46) provides energy for contractile work (actin-myosin interaction and cell shortening), pumping Ca++ back into the sarcoplasmic reticulum at the end of systole and maintaining normal ion gradients (low Na+ and high K+ in the cell). Approximately two thirds of the ATP hydrolyzed by the heart is used to fuel contractile work, and the remaining third is used for ion pumps and “housekeeping” functions such as synthesis of proteins and nucleic acids. The Ca++-ATPase of the sarcoplasmic reticulum is the primary ion pump consuming ATP. This process occurs during the end of systole, when cytosolic Ca++ is rapidly sequestered into the sarcoplasmic reticulum to initiate diastolic relaxation. In the healthy heart, the rate of ATP hydrolysis is exquisitely matched to the rate of ATP resynthesis. There is no significant change in the concentration of ATP or ADP even with the onset of heavy exercise.