PHYSIOLOGY OF CARDIAC MUSCLE 2I3 



FP, 



AH, 



SUCC 



DPN-> 

 DEHYDROG, 1 



V y 



DPNH 



FAD 



FADH 2 



FAD ^ 



CoO SHemeFe*'- 2 Heme Fe**'*2 Heme Fe+* 2HemeFe"**^ H,0 



LIPO Q II CYTO B 11 CYTO C 11 CYTO A 



CoOH, 2HemeFe-*'^'' 2Heme Fe*+ 2 Heme Fe''^ 2 Heme Fe++ 



ATP 



ATP 



ATP 



FIG. 1 5. Electron transport chain. The interrelated oxidation reductions of the hydrogen trans- 

 port enzymes are shown. The main pathway shown at the bottom is for the DPN-linked dehy- 

 drogenases. The pathways shown above are for fatty acyl-CoA derivatives and for succinate. These 

 are Ha\in-Hnked dehydrogenases. The indicated points for formation of ATP are tentative and 

 are based upon evidence available at this time. 



released or its electron (H — ► H+ + c) does not com- 

 bine immediateh' with oxygen but reacts with a 

 series of hydrogen transport enzymes in the electron 

 transport chain before combining with oxygen to 

 form water, as shown by the following over-all re- 

 action : 



kC) (15) 



DPNH + H+ -f 1,0-^ 2DPN+ -i- H.,0 -I- ^F(52 



The energy of this current of electrons is tapped off 

 at three places in the respiratory chain to form energy- 

 rich phosphate bonds. Approximately 12 kcal are 

 required to phosphorylate ADP to ATP. The terminal 

 bonds of ATP are then asailabie to the cardiac tnusscle 

 cell for performing cellular work of all kinds. 



On the basis of studies of the efTect of CN and CO 

 on the respiration of sea urchin eggs, Warburg sug- 

 gested in 1926 that an important iron-containing 

 substance (Atmungsferment) was present in cells 

 which transferred hydrogen to molecular oxygen. 

 In 1925 Keilin (116) identified three iron-heme en- 

 zymes in heart muscle by their absorption spectra 

 and named them cytochromes a, h, and c. Later, 

 Keilin & Hartree (117) found a fourth, cytochrome 

 fi. In 1932, Warburg & Christian (251) discovered 

 a flavoprotein which also participated in hydrogen 

 transport. Subsequent work by many investigators 

 (238) has revealed the presence of other hydrogen 



transport enzymes. ReccntK' a novel fat soluijle com- 

 pound, coenzyme Q (ubiquinone), a benzoquinone 

 (49, 167), with a long isoprenoid side chain has been 

 found to transfer electrons between flavoprotein and 

 cytochrome b. 



Current research on the respective positions of 

 these electron transport carriers has left certain 

 controversial questions to be settled. In general, 

 however, this outline, shown in figure 1 5, presents 

 the current working hypothesis : a DPN-linked de- 

 hydrogenase transfers hydrogen from substrate to 

 DP.\H. This DPNH then transfers its electrons to a 

 flavoprotein. The process continues by the reduced 

 FADHj transferring its electrons to coenzyme Q, 

 which in turn transfers them to cytochrome h and 

 to the other cytochromes in turn. In electron trans- 

 port bv the cytochromes, one electron is transported 

 per mole of cytochrome by oxidation-reduction of 

 the heme iron. When the electron transport chain 

 is operating at maximum capacity in the presence of 

 adequate amounts of ADP and substrate, Chance & 

 Williams (41) found that the steady-state condition 

 of the hydrogen transport enzymes, expressed in 

 terms of per cent reduction of the components, is 

 DPNH 53 per cent, FADHo 20 per cent, cytochrome 

 h 16 per cent, cytochrome c 6 per cent, cytochrome a, 

 <4 per cent. 



