Common Pathways of Cellular Metabolism - 1 55 



CH 3 



I 



c=o 



I 

 COOH 



pyruvic 

 acid 



+ CoASH + DPN 



11 

 II 

 II 



in presence of 

 carboxylase, 

 thiamine 

 pyrophosphate, 

 and other cofactors 



co 2 



+ 



CH 3 — C- 



-S-CoA + DPN-H, 



active acetyl CoA 

 intermediary 



+ 



COOH 



I 

 CH 



I 



c=o 



I 



COOH 



oxaloacetic acid 

 (4-C compound) 



// 



+ CoA-SH + DPN 



CHjCOOH 



CHOHCOOH 

 I 

 CH 2 COOH 



citric acid 

 (6-C compound) 



Fig. 8-12. Coenzyme A (CoA-SH) repeatedly trans- 

 mits activated acetyl units to the Krebs cycle. This 

 starts the cycle, converting oxaloacetic to citric acid 

 (Fig. 8-5). As is shown in Figure 8-5, the acetyl con- 

 stituent may come from the catabolism not only of 

 carbohydrate, but also of protein and fat. Also note 

 that there is a high-energy bond (~) in the acetyl-CoA 

 complex and that CoASH keeps reappearing as the 

 reaction continues. 



form mechanical, osmotic, electrical, or 

 other kinds of work, or when energy for 



chemical synthesis is needed. Finally, when 

 all the carbon of an original glucose mole- 

 cule has been discharged as CO L , and the 

 hydrogen has been oxidized to FLO, a total 

 of 16 molecules of ADP have been charged 

 with energy — that is, transformed into ATP. 

 Some of the Krebs cycle enzymes are lo- 

 calized in the mitochondrial membranes and 

 others are associated with exceedingly fine 

 particles, resolvable with the electron micro- 

 scope, suspended in the mitochondrial cavi- 

 ties. Much remains to be learned, however, 

 about the complex structural organization 

 by which the intricately coupled reactions 

 between the enzymes and coenzymes of the 

 Krebs cycle and those of the primary accep- 

 tor and cytochrome systems are executed, 

 integrated, and regulated, in subserving the 

 needs of the cell. 



SUMMARY 



Catabolism provides the cell with energy 

 as it follows a set of basic patterns that are 

 generally similar in many (perhaps all) cells. 

 Acetyl fragments and other units, derived 

 from the breakdown of proteins, carbohy- 

 drates, and fats, are transmitted to the enzyme 

 system of the Krebs cycle, mainly through 

 the agency of coenzyme A (Fig. 8-13). In the 

 Krebs cycle, a series of decarboxylation, oxi- 

 dation, and acetylation reactions, operating 

 in conjunction with the primary acceptors 

 and cytochromes of the cell, gradually dis- 

 charge the carbon of the original organic 

 substrate in the form of C0 2 and the hydro- 

 gen in the form of H 2 0. At almost every 

 step of this delicately integrated series of 

 reactions, energy is conserved by transmission 

 to the high-energy phosphate (ATP) reserves 

 of the cell. 



This basic pattern is also very important 

 from an anabolic point of view. High-energy 

 phosphate reserves permit a cell to carry on 

 energy-requiring (synthetic) reactions and 

 thus to build up the macromolecular con- 

 stituents of its structure. Many of the reac- 

 tions of catabolism are reversible. The same 



