•2o6 



HANDBOOK OF PHVSIOI.OGV 



CIRCULATION I 



HEXOKINASE PHOSPHOHEXOISOMERASE PHOSPHOFRUCTOKINASE 



glucose »■ glucose-6-P04;;3^z^z: fructose-6-PO-» ► frucfose-1,6- di-P04 



ALDOLASE 



ATP ADP 



ATP ADP 



I ISOMERASE 



dlhydroxyocetone -PO4 - D - glyceroldehyde -3- PO4 



^ -,DPN ^ 



TRIOSE PHOSPHATE DEHYDROGENASE ' 



''1 - I I ^OPNH 



I I 



D-1,3- diphosphoqlycerate 



1 i ,^ADP 



PHOSPHOGLYCERATE TRANSPHOSPHORYLASE / 



D-3- phosphoqiycerate 



PHOSPHOGLYCEROMUTASE 

 LACTIC DEHYDROGENASE PYRUVIC KINASE ENOLASE 



L(+) Inrtntp — ^ ^ pyruvate" ^' phn<;phf>pnnlpyriiuntp 'P-? - phosphoglycerate 



DPN* DPNH ATP ADP 



Fio. 9. The Embden-Meyerhof pathway for glycolysis. 



The enzyme aldolase converts fructose- 1 ,6-diphos- 

 phate to a mixture of two triose phosphates, dihydrox- 

 yacetone phosphate, and glyceraldehyde phosphate. 

 A triose phosphate isomerase catalyzes the inter- 

 conversion of the two. The oxidation reduction 

 in anaerobic glycolysis involves the oxidation of 

 D-glvceraldehyde- 3 -phosphate in the presence of 

 inorganic phosphate and DPN+ to d , i ,3-diphos- 

 phoglyceric acid and DPNH. The d , 1-3-diphos- 

 phoglyceric acid then reacts with ADP to yield 

 D,3-phosphoglyceric acid plus ATP. A second mole 

 of ATP is formed subsequently through the hydrolysis 

 of phosphoenolpyruvic acid to pyruvic acid. In 

 anaerobiosis (which is rare in cardiac muscle) the 

 DPNH formed in the oxidation of D-glyceraldehyde- 

 3-phosphate is oxidized by pyruvate to form lactate 

 with the regeneration of DPN+. Usually the DPNH 

 formed aerobically via glycolytic reactions is oxidized 

 by sarcosomal DPN"^ to initiate the transport of this 

 hydrogen to Oo. 



As noted above, two high energy phosphate bonds 

 are derived from each mole of triose glycolyzed, i.e., 

 four per mole of glucose. The net yield of ATP in 

 glycolysis, however, is 2 moles of ATP per mole of 

 glucose, since 2 moles of ATP are required by the 

 kinases. The limited formation of ATP represents 

 an over-all energy liberation in glycolysis of only 



9 per cent of the energy content of glucose. The over- 

 all reactions of glycolysis can be written : 



glycolytic 

 enzymes 



Glucose -i- 2 ATP + 2 P, + 2 ADP :^ 



(0 



2 lactate + 4 .\TP 



In addition to the enzymes themselves, and their 

 cofactors (168), it is obvious that any of the four 

 terms on the left side of the equation may limit the 

 rate of glycolysis (199). In the intact heart, because 

 of the very vigorous oxidative phosphorylation oc- 

 curring in the sarcosome (248), ADP is most likely 

 to be limiting. In general, the concentrations of the 

 glycolytic enzymes in cardiac muscle are not as high 

 as those of .skeletal muscle (Appendix table), although 

 evidence to decide whether enzyme concentrations 

 are actually limiting under in vivo conditions is 

 lacking for the cardiac muscle cell. 



Under aerobic conditions, which are essential for 

 in vivo activity of heart muscle, the terminal re- 

 action of glycolysis, i.e., the reduction of pyruvate, 

 does not occur. In fact, lactate and glucose are simul- 

 taneously extracted from the coronary blood and 

 metabolized to carbon dioxide and water. This 

 suggests that the capacity of the sarcosome for hydro- 

 gen transport greatly exceeds the glycolytic rate 

 under the usual conditions. The sarcoplasmic DPNH, 



