PHYSIOLOGY OF CARDIAC MUSCLE 



CoA-S-C-CHj 



CoA-SH 

 oxaloacetote/'"^cifrate 



FADHj 



FAD- 



ATP 



p. + ADP'^ "^GDP 

 ' CoA-SH 



cis-aconifate 



isocitrate 



gjp succinate 



oxalosuccinote 



oC- ketoglutorote 

 CO, 



^DPN 

 V^DPNH 



FIG. 14. The Krebs citrc acid 

 cycle. 



DPNH 



DPN"^ 



of the cycle, as indicated earlier, is to convert the 

 bond energy of the acetyl moiety of acetyl-CoA to 

 I mole of ATP and to DPNH and FADH. bound 

 electrons for transport to oxygen via the electron 

 transport chain. The cycle thus accomplishes the 

 reaction : 



CH3CO— S— Co.\ + 3DPN+ + FAD + 3H2O +ADP 



+ P, ^ 2CO2 + CoASH + 3DPNH (8) 



+ F.ADH; + 3H+ + .^TP 



The dehydrogenases of the citric acid cycle are all 

 contained in the mitochondrion and, with exception 

 of succinic dehydrogenase, are all DPN-dependent. 

 The TPX-dependent isocitric dehydrogenase (170) 

 isolated from heart is found in the cytoplasm (212). 

 All of the dehydrogenase of the citric acid cycle are 

 present in heart muscle in high amount, reflecting 

 the large number of cardiac sarcosomes as well as 

 their richness in hydrogen transport enzymes. The 

 cofactors for enzymes of the citric acid cycle, thiamine- 

 pyrophosphate (TPP), coenzyme A (C0A-.SH), di- 

 phosphopyridine nucleotide (DPN), and flavin- 

 adeninedinucleotide (F.\D) are all abundantly present 

 in cardiac muscle. Comparative data for the.se co- 

 enzymes or their vitamin constituents for heart and 

 skeletal muscle are shown in the Appendix table. 

 It is obvious that depletion of these coenzymes through 



severe B-complex vitamin malnutrition could seri- 

 ouslv reduce the capacity of the heart for energy 

 production. 



In the oxidation of glucose, 35 per cent of the bond 

 energy of the molecule is released (2 moles of net 

 ATP at the substrate level in glycolysis and 4 moles 

 of DPXH formed in lactic and pyruvic dehydro- 

 genations) prior to the formation of acetyl-CoA. In 

 the Krebs cycle the remaining 65 per cent of the 

 energy of glucose is transformed into 2 moles of ATP 

 (formed in the phosphorylation of ADP by succinyl- 

 CoA) 6 moles of DPNH, and 2 moles of FADH-.. 

 The release and conservation of the energy stored in 

 pyridine and flavin nucleotides is accomplished in 

 the process of electron transport to oxygen. 



AMINO ACID OXIDATION. Amino acids do not provide 

 a major source of energy for cardiac muscle. Intra- 

 cellular cardiac amino acid metabolism is not brisk 

 and dcamination is minimal. The intermolecular 

 transfer of amino groups is particularly active in 

 cardiac muscle, howe%'er, due to the presence in 

 large amounts of two transaminases, glutamic-oxalo- 

 acetic transaminase (GOT) and glutamic-pyruvic 

 transaminase (GPT). These enzymes provide a portal 

 of entry of amino acid carbon into the tricarboxylic 

 acid cycle at three points, i.e., alanine — >pyruvate; 

 aspartate — 'oxaloacetic, and glutamic — >ketoglutaric 



