HENRY R. MAHLER 



secutively to bring about the complete multistep conversion of 

 a substrate, are linked together to form part of the mitochon- 

 drion seems commonplace to us today. Yet neither the thought 

 nor its experimental verification had been attempted ten years 

 ago. I do not wish to belabor the point — reviews on the topic 

 of the mitochondrial enzymes are plentiful (14,22,37). I 

 simply wish to stress the thought that there is the germ of novelty 

 inherent already in the term "mitochondrial enzyme." The 

 subsequent discussion is fully intended to be provocative rather 

 than enumerative.* The interpretations of the experimental 

 work presented lay no claim either to uniqueness or correctness. 

 They are merely intended to point at possibilities, rather than 

 probabilities; possibilities which may at least have the virtue 

 of suggesting fruitful approaches for further experimentation. 



Let us assume then that enzyme complexes exist within the 

 mitochondrion, and that their primary purpose is to effect 

 efficient multistep transformations subject to the homeostatic 

 and control mechanisms of the cell. What are the methods 

 available to us to study the nature of these transformations; 

 how are we to approach the individual enzymatic process; 

 and how are we to arrive at an understanding of the interaction 

 of the several individual processes making up the whole? 



The first method, an essentially dynamic one, proposes to 

 refine our observational tools to such an extent that we may 

 observe individual or sequential reactions with the mitochon- 

 drion in situ, without disturbing the array at all. These tools, 

 honed to fine perfection in the hands of Chance (7) then permit 

 us to study the kinetics not only of over-all reactions but also of 

 the individual component reactions. As with all studies of 

 mechanisms based on kinetics a study of this sort limits the 

 number of mechanisms to those which are consistent with the 

 kinetic data but does not allow us to make a choice between 

 the various permissible mechanisms. Individual reactions can 



* No review of the literature will be attempted. The only references 

 actually cited are to reviews or to those papers which present a particular 

 point of view cogent to the argument at hand. 



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