ENZYME COMPLEXES 



can give us information about relationships and over-all meta- 

 bolic sequences. It is not designed to increase our knowledge 

 about the fine structure of individual enzyme-catalyzed reactions 

 too far. Little can be learned about the fundamental chemical 

 changes within the enzyme-substrate complex which must be 

 the prime cause of this catalysis. For studies of this sort we must 

 rely on observations on highly purified individual enzymes. 

 But we must realize that by so doing we may lose sight of the 

 role of this one specified catalysis in relation to other catalytic 

 events, and that in the process of isolation we may have changed 

 the very nature of the catalysis as it originally existed. Thus 

 the proper experimental and conceptual approach demands 

 the use of successive approximations derived in an alternating 

 and synergistic manner both from studies on integrated systems — 

 with their inherent inadequacies — and on highly purified, 

 isolated enzymes — with their attendant drawbacks. 



Can we find footholds in this continuous process of oscillation 

 between the grand but blurred vista of the whole and the sharply 

 defined but myopic study of the individual? In enzyme chemis- 

 try, more precisely in the study of oxidative, mitochondrial en- 

 zymes there fortunately are such halfway points. There too it has, 

 of course, frequently been possible to isolate highly purified 

 enzyme preparations carrying out just one reaction of a sequence 

 in a completely determined manner, in line with the tenets of 

 classical enzyme chemistry. The remarkable fact is that it has 

 also been possible, in certain instances at least, to isolate just as 

 well-defined and characterized complex enzymes capable of 

 catalyzing complex, sequential reactions. 



Such enzymes frequently contain more than one prosthetic 

 group or coenzyme and in all cases almost by definition, must 

 contain more than one site involved in enzymatic activity. This 

 fact, together with the observation that if tlie enzyme is obtained 

 from a different source — ^frequently bacterial in origin — or if a 

 different isolation procedure is followed, it is sometimes possible 

 to resolve the preparation into more than one protein com- 

 ponent, has been used to argue against a definite unitarian 



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