BIOCHEMICAL REACTIONS AND THEIR CATALYSTS 117 



not necessarily have the same affinity for the different apoenzymes which 

 it activates. 



The most stable type of combination might result from the formation 

 of an ester or amide from the two components; more labile unions could 

 resemble those found in compounds which dissociate readily in aqueous 

 solution — hemiacetals, ammonia-aldehyde types, and hydrates; the bond- 

 ing in some systems whose degree of dissociation is so sensitive to 

 electrolyte concentration and pH changes might be explained by ionic 

 attraction and salt formation. 



Until recently no one had ever questioned the assumption that the 

 union of a substrate and its enzyme was one involving actual physical 

 contact of the two molecules. However, it has been reported that enzymes 

 whose surfaces were believed to be completely coated with a polymer 

 film could still activate their substrates and effectively catalyze re- 

 actions. 22 That this procedure prevented the physical union between 

 enzyme and substrate has been challenged; 23 but if this finding can be 

 substantiated and shown to be of general application to enzyme systems, 

 many current concepts concerning enzyme mechanisms, including the 

 functioning of coenzymes, will have to be radically altered. 



Any theory concerning the chemical and physical forces which bind the 

 components during a reaction should account for the extreme specificity 

 which the protein may exhibit in its choice of substrates. Often, the 

 slightest alterations in the structure of a substrate or coenzyme will 

 affect its capacity for uniting with the enzyme, even though no change 

 has been made in any of its reactive groups or the isoelectric point. This 

 is indicative that the spatial configuration is critical. 



The similarity in the chemical composition of the nonvitamin moiety 

 of all the coenzymes is indicative of a general requirement for phosphate 

 ester and adenylic acid components in the establishment of the coenzyme- 

 apoenzyme bond. The additional acid and amino groups introduced when 

 the coenzyme is created increase the number of points where the coenzyme 

 molecule can become attached to the protein by the formation of a salt. 

 Perhaps adenylic acid possesses a chemical structure which is particularly 

 adapted for combining with some configuration common to a number of 

 proteins. Thus adenylic acid itself serves as a coenzyme for some reactions 

 p. 134) ; its phosphorylated derivatives are essential dissociable parts of 

 most enzyme systems in which high-energy phosphate bonds are created 

 or utilized; and nucleic acids which contain adenylic acid constitute the 

 prosthetic groups of a number of important types of proteins. 



There is a difference in the affinity of apoenzymes for the oxidized and 

 reduced states of the coenzymes of nicotinic acid. This can be attributed 

 at least partly to the acid-base changes which accompany the oxidation 



