CHAPTER V 



METABOLIC CYCLES AND CHAIN REACTIONS 



Such metabolic effects as the conversion of glucose to lactic acid or carbon 

 dioxide are not simple one-stage reactions, but are made up of a complicated series of 

 processes which are interrelated and which require at the appropriate stages the 

 co-operation of many different enzymes, coenzymes and substrates. When the com- 

 plete enzyme system for each reaction has been assembled at the proper stage in the 

 cycle the necessary energy relationships required from thermodynamic considerations 

 must be observed, so that one reaction may be coupled with another to provide and 

 absorb the essential free energy changes. In addition the coupling together of reactions 

 is necessary to provide for the gathering together of the substrates and the removal 

 of the reaction products to prevent stagnation by the accumulation of products of the 

 forward reaction. 



To summarise therefore : for each of the reactions in the chain to proceed 

 smoothly it is essential to provide : — 



(1) Suitable pH, temperature, ionic concentrations. 



(2) Synthesis of specific enzyme and coenzyme at the right time. 



(3) Production of reactants by previous reaction in chain. 



(4) Removal of products by succeeding reactions. 



(5) Provision or removal of free energy by coupled reactions. 



(6) The bringing together in intimate contact in space of reactants, enzymes, 

 coenzymes, coupled reaction products and free energy simultaneously. 



(7) The absence of reaction inhibitors and poisons. 



Some of the necessary factors have been considered piecemeal in the preceding 

 chapter and typical metabolic cycles that have been studied in some detail will 

 indicate how some of the isolated facts can be synthesised into a larger scheme even 

 though knowledge is still fragmentary and liable to revision. 



Before discussing metabolic cycles it is necessary to consider the important 

 position active phosphate groups play in energy changes and storage in metabolism. 



ENERGY RICH PHOSPHATE BONDS 



Lipmann (1941) has been responsible for developing the concept of the importance 

 of energy-rich phosphate bonds in carbohydrate metabolism. 



In the first chapter the free energy of chemical reactions was dealt with. It was 

 pointed out that the change in free energy in a reaction is the important factor and 

 not the total heat change. It is possible to have two compounds with the same total 

 energy content, but the reactivity of the two may be entirely different owing to the 

 different distribution of the energy among the various interatomic linkings. If in the 

 breaking of a linkage a large amount of free energy is liberated the group linked will 

 tend to be highly reactive. 



The free energy content of the phosphate linking in phosphate esters is compara- 

 tively low, of the order of 3,000 calories, and these are designated energy-poor phos- 



