74 



Cellular Structure and Activity 



carried out successfully, all components — phos- 

 phate, triose, oxidized DPN, ADP and the appropri- 

 ate enzymes — must be present. In the absence of 

 DPN the oxidation will not take place; in the ab- 

 sence of phosphate and phosphate acceptor, on the 

 other hand, or in the presence of a competing sub- 

 stance for phosphate, such as arsenate, the oxidation 



Glucose 



Glucose- 6- Phosphate 



Lactate ^ ±2H^ — 



After rearrangement and addition of water, phos- 

 phoenolpyruvic acid is formed from phosphogly- 

 ceric acid. Phosphoenolpyruvic acid contains a high 

 energy phosphate linkage. In the presence of ADP, 

 transphosphorylation occurs to yield pyruvic acid 

 and ATP. Enolase, the enzyme leading to the forma- 

 tion of the enol form, is especially sensitive to fluor- 



-2r -CO2 



.Malate 



-CO2 



Oxalacetate 



PYRUVATE 



I 

 PROTEIK 



I I .1 



Acetoacetate, 



A 



Fig. 5. Pathways in the metabolism of pyruvate. (From Barron.) 



takes place without the formation of a utilizable 

 energy packet. Phosphoglyceraldehyde oxidase is 

 highly sensitive to iodoacetic acid (lAA) and re- 

 lated compounds — hence the special virtue of lAA 

 in preventing glycolysis. This type of interplay of 

 enzymes, cofactors, and substrates is found repeat- 

 edly throughout oxidation of foodstuffs, and usually 

 the same coenzyme systems are present. It is a re- 

 markable fact that adenylic acid systems (DPN 

 contains ADP in its molecule) are so widely spread 

 throughout living matter (cf. Barron, '43). The 

 nitrogenous base coenzymes, diffusible and labile, 

 are nucleotide systems containing phosphate, nitrog- 

 enous base and pentose sugar. In their role as co- 

 factors for enzyme proteins, these complexes must 

 bear a rather interesting relationship to the nucleo- 

 proteins. 



ide ion, the fluoride forming a complex with phos- 

 phate and with magnesium, an essential part of the 

 active enzyme. Thus, from the addition of fluoride, 

 the formation of two molecules of pyruvate from 

 one molecule of hexose diphosphate is accompanied 

 by the formation of four ATP energy-rich phos- 

 phate bonds together with the reduction of two 

 molecules of DPN. [Cf. a discussion by McShan in 

 Lardy ('50) on the roles of DPN and TPN.] 

 To start with simple nonphosphorylated hexose, the 

 preliminary phosphorylation would require the 

 utilization of two molecules of ATP phosphorus, 

 giving a net gain of two rather than four energy- 

 rich bonds. With glycogen as an original substrate, 

 having glucosidic linkages already established, only 

 one labile phosphate is required to convert each 

 glucose residue to hexose diphosphate. Hence the 



