SOME TOPOGRAPHICAL ASPECTS OF THE 

 REGULATION OF CELL METABOLISM 



C. DE DUVE 



Laboratory of Physiological Chemistry, University of Louvain 



Life has been defined by Hopkins as "a dynamic equili- 

 brium in a poly phasic system". For many years, the efforts 

 of biochemists have been mostly directed toward a proper 

 elucidation of the first half of this definition. They have 

 indeed been uncommonly successful and expressions such as 

 steady state, limiting step, key reaction, alternative pathways, 

 competition, coupling, feedback, have become standard parts 

 of a new jargon of biochemical cybernetics. 



With the advent of electron microscopy and of differential 

 centrifugation, it has become possible to explore also the 

 second part of Hopkins' definition, which corresponds to the 

 structural factors of cellular organization. These must be 

 considered as bringing additional levels of complexity and 

 new sets of relationships into systems which are already 

 strongly organized by virtue of the multiple dynamic relation- 

 ships existing between their various components. 



One of the simplest consequences of structural organization 

 is the fact that given groups of enzymes are associated to- 

 gether and separated from others. That most enzymes are 

 indeed segregated in this manner has been abundantly verified 

 in recent investigations, but the results obtained have not 

 always been as clearcut as our desire for simplicity and con- 

 formity would have them to be. As pointed out in previous 

 reviews (de Duve and Berthet, 1954; de Duve, 1957), insuf- 

 ficient resolution of the separation methods and of the assay 

 procedures, together with other technical difficulties and 

 artifacts, are partly responsible for this state of affairs. There 

 are, however, other causes, amongst which our ignorance and 



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