The Nature and Diversity of Catalytic Proteins 85 



thiokinase reaction can be visualized as occurring with participation 

 of one key transition state, as depicted in Fig. 6. The reactants are 

 bound in an activated form, and as the acetate carboxyl oxygen 

 approaches the P atom of the ATP, the S of coenzyme A approaches 

 the acetate carboxyl carbon, with the formation of the products in one 

 concerted reaction. This is in contrast to the reaction as usually 

 depicted with acetyl adenylate as a discrete intermediate (see ref. 

 34 ) . Participation of such an intermediate would appear to necessitate 

 rather complicating shifts of the reactants during catalysis. An attempt 

 to depict this difficulty is given in Fig. 7. For discrete formation of 

 acetyl adenylate, the S atom of the bound and activated coenzyme 

 A molecule must somehow be held away from the acetate carboxyl 

 carbon, which would become increasingly susceptible to reaction as its 

 oxygen departed for cleavage of the ATP. Then after acetyl adenylate 

 had formed, a shift would need to occur, to allow the coenzyme A and 

 acetyl adenylate to react. 



The manner by which the synthetases and much simpler enzyme 

 systems react is obviously far from settled. The recognition of sub- 

 strate release as potential slow steps in the catalyses, together with 

 other information, warrants the hypothesis that enzyme reactions in 

 general may proceed through binding of reactants favoring reaction 

 through one key transition state (4) . 



A similarity of oxidative phosphorylation 

 and muscle contraction 



For a number of years our group has been interested in the basic 

 problem of how oxidative enzymic reactions are coupled to formation 

 of ATP, visually referred to as oxidative phosphorylation. Not being 

 content with having one seemingly insoluble problem on our hands, 

 we recently undertook some experiments related to muscle contraction. 

 The divergence is not as wide as it might seem, and one principal 

 reason for our interest in ATP cleavage by myosin and actomyosin 

 was the finding by Levy and Koshland (35) that an unexplained 

 oxygen exchange reaction accompanied the cleavage. 



Several years ago in studies on oxidative phosphorylation by mito- 

 chondria, the discovery was made that the process was characterized 

 by a rapid exchange of inorganic phosphate with ATP as well as a 

 much more rapid exchange of phosphate oxygens with water. Typical 

 results are given in Table 5. Such rapid exchange of phospbate 

 oxygens is unusual, and one possible explanation may be the rapid 

 formation and hydrolytic cleavage of a phosphorylated intermediate. 



