APPROACHES TO THE ANALYSIS OF SPECIFIC MEMBRANE TRANSPORT 587 



process of diffusion down the electrochemical activity gradient "trans- 

 location catalysis". When we describe the transport of a substance as 

 "active", it is because we do not know (or do not w^ish to specify) in what 

 form the substance actuallv diffuses across the membrane. 



SUBSTR.\TE AND SUBSTRATUM SPECIFICITIES OF ENZYMES 

 AND CATALYTIC CARRIERS 



The view that I have been developing of substrate and group trans- 

 location as part of the metabolic process in the spatially organized enzyme 

 and catalytic carrier systems of the membrane complex, places the problem 

 of membrane transport in a new light, for it suggests that to picture the 

 process of transport at the molecular level of dimensions we need to 

 recognize, not only the substrate specificities of the enzymes and catalytic 

 carriers as normallv understood, but also the locational or substratum 

 specificities that are responsible for bonding these components into the 

 organized structure of the membrane complex [36]. The locational bonds 

 may be said to represent the articulations between the bones of the 

 cytoskeleton [39]. 



The conception of the bivalent specificity (the substrate specificity on 

 the one hand and the substratum specificity on the other) of the trans- 

 location catalysts stems directly from considerations of the transport 

 process per se. It is, perhaps, significant that when one considers the 

 transport process from a different angle, that is, in relation to growth and 

 adaptation (as we are asked to do in this session of the Symposium), the 

 same type of conception as I have just outlined seems to be required. For, 

 since it is inconceivable that the catalysts of translocation could all be 

 synthesized at the sites of their activity in the membrane, the very catalytic 

 components of a membrane system that are to cause and control the 

 translocation of a specific substrate must, themselves, possess the speci- 

 ficities that will cause them to be transported to and incorporated in the 

 organized membrane structure during growth and adaptation. As I 

 pointed out some years ago [2, 4], one must take much more care than has 

 been customary in interpreting the results of studies of mutants that lack 

 particular transport capacities, for loss of a transport capacity could as 

 easily be due to a change of locational specificity between a transport- 

 catalyzing enzyme or carrier and its locator region (substratum) in the 

 membrane as to the loss of the catalytic function of the free enzvme or 

 catalytic carrier molecule itself. 



I propose now to summarize the results of two series of experiments 

 bearing on the problem of enzyme location and enzyme-substratum 

 specificity that we have recently done in Edinburgh. It has been customarv 

 to assume that intracellular enzymes which appear in solution in the 



