GENERAL SUMMARY 



given transport site and to monitor its isolation. Perhaps an amino 

 acid analog can be constructed that will first bind as usual at the 

 transport site, and then either spontaneously, or upon irradiation 

 or other special treatment, bond itself stably to adjoining parts of 

 the mediating structure. Means are then available through isotope 

 labeling to intensify the specificity of such markers. 



One must bear in mind that the molecules involved in transport 

 mediation are probably insoluble and macromolecular. They are 

 likely to be either embedded in or integral with the membrane 

 structure. Therefore isolative procedures probably must solubilize 

 the components, a procedure that may well destroy their function. 

 Two lines of analytical effort can be foreseen: one to separate, with- 

 out the necessity of preserving function, the stably marked mediat- 

 ing structure; the other to use the persistence of at least an aspect 

 of transport behavior to guide the isolation of a component. Obvi- 

 ously, in the latter approach, a narrower range of procedures will 

 be applicable. The preparation of artificial lipid or lipoprotein bar- 

 riers, and the study of their transport properties, are other promising 

 approaches. 



A general exploration of the nature of the structure of the 

 plasma membrane may uncover further technical means of separat- 

 ing components functioning in transport. For such exploration we 

 should probably select membranes with minimal metabolic potenti- 

 alities other than transport; for example, the red blood cell mem- 

 brane is functionally much simpler than membrane preparations 

 obtained so far from bacteria. In mutants lacking a given transport, 

 attention will fall on the absence of any component possessed by 

 the wild type. 



Given that an uphill transport may represent in its totality an 

 ATPase activity, we may be led to the mediating structure by fol- 

 lowing the course of the terminal phosphoryl residue of ATP up 

 to the point where it finally appears as inorganic phosphate. For 

 example, a membrane lipoprotein in which the contained diglyceride 

 can be phosphorylated to yield a phosphatide acid may prove to 

 be a key component. No doubt such lipoproteins will be studied for 

 their ability to bind specifically solutes undergoing uphill transport. 



But if, instead, the cleavage of ATP is per se a vectorial event, 

 as Mitchell suggests, occasioning the migration of hydroxyl ion 

 across a barrier, the receptors of the resultant phosphoryl group 

 may have only secondary significance, and the structures linking 



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