Extraneous Agents and Cell Metabolism 95 



glyceraldehyde, a powerful inhibitor of glycolysis (Mendel, 

 1929; Rudney, 1949). L-Glyceraldehyde is transformed in 

 glycolysing material into L-sorbose-1 -phosphate under the 

 influence of aldolase, d -Glyceraldehyde probably inhibits 

 triosephosphate dehydrogenase (Needham, Siminovitch and 

 Rapkine, 1951). 



Whilst pacemakers are more vulnerable to extraneous 

 agents than non-pacemaker reactions, the latter are not 

 immune to inhibitors; but a substantial proportion of a 

 non-pacemaker must be inactivated before the overall rate is 

 affected. An inhibitor of glycolysis which interferes with a 

 non-pacemaker is fluoride. It inhibits enolase, the enzyme 

 which converts 2 -phosphogly cerate to enolphosphopyruvate 

 (Meyerhof and Kiessling, 1933; Lohmann and Meyerhof, 

 1934). However, fluoride also inhibits other enzymes, in 

 particular those dependent on magnesium ions as a cofactor, 

 such as adenosine triphosphatase and some phosphate-trans- 

 ferring enzymes. It is by no means established that the in- 

 hibition of glycolysis is solely due to the inactivation of enolase. 



Effects of extraneous agents on cell respiration 



When energy is released by the oxidation of carbohydrate, 

 fat and amino acids, there are over a hundred identifiable 

 intermediate steps, only a few of which are pacemakers. The 

 non-accumulation of intermediates indicates that those steps 

 which initiate the oxidation of a substrate, i.e. the reaction 

 between substrates and their dehydrogenase, must be among 

 the pacemakers of respiration. Once the oxidation has been 

 started, most of the subsequent reactions, leading to complete 

 combustion, follow at the pace set by the initiating step, 

 owing to the excess of enzymes dealing with the intermediary 

 products. The initiating reactions also decide which sub- 

 strate among a mixture is attacked preferentially — whether 

 carbohydrate, fatty acid or amino acids serve as a source of 

 energy. In addition, pacemakers are expected at two other 

 types of stages of the oxidative metabolism, at those where the 



