The cardiac myocyte utilizes various pathways for the production and utilization of adenosine triphosphate (ATP). Fig. 16.46 illustrates the overall scheme for these processes. It shows the pathways for the utilization of glucose, fatty acids, and lactate, as well as the requirements for oxygen and hydrogen ions by the electron transport chain in mitochondria. The figure also includes the involvement of various enzymes and molecules such as ADP, coenzyme A, carnitinepalmitoyltransferase, glucose-6-phosphate, glucose transporter, nicotinamideadenosinedehydrogenase, pyruvatedehydrogenase, inorganic phosphate, sarcoplasmic reticulum, triglyceride, and ATPase. The ATP produced is utilized for contractile work, sarcoplasmic reticulum calcium ion uptake, and ion homeostasis. The ATP hydrolysis process involves glycolysis, fatty acid oxidation, citric acid cycle, electron transport chain, and triglyceride breakdown. Despite the high rate of ATP hydrolysis, the healthy heart maintains a relatively constant level of ATP. This level is low compared to the rate of breakdown and production, with complete turnover of the myocardial ATP content occurring approximately every 12 seconds at rest. ATP hydrolysis provides energy for contractile work, calcium ion pumping, and maintenance of normal ion gradients. Around two-thirds of the ATP hydrolyzed by the heart is used for contractile work, while the remaining third is utilized for ion pumps and other cellular functions. The primary ATP-consuming ion pump is the sarcoplasmic reticulum Ca++-ATPase, which sequesters cytosolic calcium ions during diastolic relaxation. The rate of ATP hydrolysis is closely matched to the rate of ATP resynthesis in a healthy heart, leading to no significant change in ATP or ADP concentration even during heavy exercise.
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.