PHYSIOLOGY OF CARDIAC MUSCLE 



209 



p glycogen -^ 



glucose 



ftTP 



gluccse-6-PQ," 



phosphorylase Q 



(DESRANCHING ENZYME) 



AMYL0(I,6) -GLUCOSIDASE 



AOP ATP 



PHOSPHOGLUCO- 

 MUTASe 



glucose -I- PO4 



U T P-e- 



glycogen 



AMYLO (1:4 -1:6 1- 

 TRANSGLUCOSIDASE 



glycogen „ 



UDPG - PYRO- 

 PHOSPHORYLASE 



glycolysis 



-». uDP — g lucose 



glycogen 



(n-l) 



FIG. 12. Pathways for glucogenesis and glucogenolysis in cardiac muscle. 



primarily as sarcoplasmic granules. The glycogen 

 content of muscle ordinarily ranges from 0.4 to 0.6 

 per cent of the fresh tissue weight (220). Cardiac 

 glycogen level is maintained very constant under a 

 variety of conditions including those which tend to 

 deplete glycogen in liver and skeletal muscle, such 

 as prolonged fasting (145) and diabetes (114). Under 

 the influence of glucose plus insulin the cardiac 

 glycogen may rise as high as 1.2 per cent (43). After 

 cardiac arrest or acute anoxia, due to coronary liga- 

 tion, cardiac glycogen falls with the formation of 

 lactic acid via the reactions of glycolysis. The work- 

 ing heart demonstrates more rapid glycogenolysis 

 than the quiescent excised heart under anoxic con- 

 ditions (28). It has been suggested h\ Bloom et al. 

 (28, 207) (on the basis of differential extractibility 

 of muscle glycogen by trichloracetic acid and KOH 

 after tissue digestion) that two forms of glycogen 

 exist in muscle tissue, one labile and e.xtractible by 

 TCA and one fixed to protein and extractible only- 

 after digestion. In the dog heart (43, 155) the TCA- 

 extractible fraction is about 80 per cent of the total 

 and appears to be more labile physiologically under 

 conditions favoring both glycogenesis and glycogenol- 

 ysis. It is possible that the labile fraction exists as 

 free granules in the sarcoplasm, whereas the stabile 

 fraction is bound to one of the organelles or other 

 structure. 



Glycogenesis and glycogenolysis occur via separate 

 pathways in cardiac muscle. These are presented in 

 figure 12. Glucogenesis from glucose-6-phosphate in- 

 volves four enzymatic steps. First the glucose-6- 

 phosphate is corrected to glucose- 1 -phosphate by 

 phosphoglucomutase. The glucose- 1 -phosphate then 

 reacts enzymatically with uridinetriphosphate to give 



UDP-glucose plus pyrophosphate. An enzyme known 

 as UDPG-glycogen transferase then transfers a glucose 

 residue from UDPG to an oligosaccharide to give 

 a 1:4 glucoside of this oligosaccharide (glycogen). 

 The branching enzyme amylo, -1:4 to i :6-trans- 

 glucosidase then creates a branch point in the glycogen 

 molecule by transferring a glucose residue from the 

 linear i '.\ sequence to a 1:6 linkage. In this way the 

 glycogen molecule is built up. The UDP formed in the 

 sequence is rephosphorylated to UTP by reaction 

 with ATP. 



Glycogenolysis is the result of the action of two 

 different enzymes, phosphorylase and the debranching 

 enzyme (i ,6-amyloglucosidase). Phosphorylase a, the 

 biologically active form of the enzyme from skeletal 

 muscle has a molecular weight of 500,000. It is 

 formed from the inactive phosphorylase h, which has 

 a molecular weight of 250,000 (118) by an .ATP 

 driven kinase which phosphorylates the inactive 

 enzyme and forms a dimer which is active. This re- 

 action is shown below : 



kinase 



2 phosphorylase b -{■ \ .-XTP > 



Mn++ (^) 



phosphorylase a -|- 4 .■\DP 



The reversal of this reaction, i.e., the breakdown of 

 phosphorylase a to phosphoryla.se h is catalyzed by 

 another enzyme known as the PR enzyme viz : 



PR enzyme 

 phosphorylase a '- * 2 phosphorylase 6 -|- 4 P^ (6) 



The presence of PR enzyme in muscle tends to retard 

 glycogenolysis by inactivating phosphorylase. 



Epinephrine is instrumental in stimulating phos- 



