PHYSIOLOGY OF CARDIAC MUSCLE 



205 



FIG. 8. Schema of energetics 

 in cardiac muscle. [From Olson 

 & Piatnek (181).] 



of the sarcosome. The phase of energy conservation 

 includes mainly the process of oxidative phosphoryla- 

 tion by which the electronic energy of hydrogen is 

 converted into the terminal bond energy of adeno- 

 sinetriphosphate (ATP) and creatine phosphate (CP). 

 Some storage of energy as glycogen occurs at the 

 substrate level in cardiac muscle and may also be 

 included as a process of energy con.servation. 



The phase of energy utilization includes the mecha- 

 nisms by which the high energy phosphate bonds of 

 ATP are channeled into a variety of anabolic proc- 

 esses involving performance of chemical work and 

 into the contractile process which i-e.sults in mechani- 

 cal work. Although there is considerable controversy 

 about the model which best represents the contractile 

 system (133, 167, 250), the model presented in figure 

 8 is consistent with most of the facts which have been 

 determined experimentally and which are discussed 

 below. 



Energy Liberation 



The pathways leading from oxidizable metabolite 

 in the coronary blood to the final electron transport 

 chain of enzymes in the cardiac sarcosome include 

 a) glycolysis via Embden-Meyerhof schema, b) fatty 

 acid oxidation, and c) terminal oxidation of fatty 

 acid and carbohydrate carbon via tlie Krebs cycle. 

 The glycolytic enzymes are found in the sarcoplasm, 

 whereas the enzymes of fatty acid oxidation, pyruvic 

 acid oxidation, and those of the tricarboxylic acid 

 cycle are located in the sarcosome. The function of 

 the electron transport enzymes themselves will be 

 considered in the section on energy conservation. 



GLUCOSE METABOLISM. The metabolism of glucose is 

 initiated in heart muscle, as in most tissues, by the 



action of hexokinase, an enzyme which phosphorylates 

 glucose with the aid of ATP to gIucose-6-phosphate. 

 Hexokinase is associated with both the soluble and 

 the particulate portions of the cardiac muscle cell 

 (50). The particulate hexokinase is probably asso- 

 ciated with sarcolemma fragments and acts to facilitate 

 the transport of glucose across the membrane. The 

 product of the hexokinase reaction, glucose-6-phos- 

 phate, is a key metabolite because it may a) be con- 

 verted to glycogen, h) be glycolyzed via the Embden- 

 Meyerhof schema shown in figure 9, or c) undergo 

 direct oxidation via the reactions of the Warburg- 

 Dickens hexosemonophosphate shunt (55, 105, 198). 

 Hydrolysis of glucose-6-phosphate to glucose, a re- 

 action characteristic of liver and kidney, and de- 

 pendent upon glucose-6-phosphatase, does not occur 

 in cardiac or skeletal muscle because of the absence 

 of the phosphatase. Pathways [a] and {c) which are 

 pathways of less importance in the heart will be dis- 

 cussed subsequently. 



Glycolysis. The reactions of the Embden-Meyerhof 

 pathway are well presented in a variety of standard 

 textbooks of ijiochemistry (74) and summarized in 

 figure g. Following the initial phosphorylation, 

 glucose-6-phosphate undergoes an isomerization to 

 fructose-6-phosphate catalyzed by the enzyme phos- 

 phohexoseisomerase. The second phosphorylation of 

 glycolysis catalyzed by phosphofructokinase, and 

 driven by ATP, converts fructose-6-P04 to fructose- 

 I ,6-diphosphate. Olson (182, 183) has presented 

 evidence that strongly suggests that phosphofructo- 

 kinase is the limiting enzyme of glycolysis in liver, a 

 ti.ssue with a relatively low glycolytic rate, and Cori 

 (46) and Neifakh & Melnikova (169) have claimed 

 that this same enzyme limits the maximum over-all 

 rate of glvcolvsis in muscle. 



