578 BERNARD D. DAVIS 



A second, more serious objection to the term "permease" is its impli- 

 cation that the transport system is an enzyme. Here a good deal of history, 

 from zymase to methionine synthase, has sensitized biochemists to the 

 distinction between an enzyme and a more complex system. Finally, while 

 one can argue w^hether or not the term "enzyme" should be restricted to 

 catalysts that change a covalent bond in a substrate, there is general agree- 

 ment that the term is not usefully applicable to such proteins as haemo- 

 globin, which only form a loose, reversible association with their substrate. 

 And we must at present not restrict our thoughts on models for specific 

 transport to those in which the permeant is enzymically converted into 

 another compound at one side of the membrane and restored again at the 

 other side; we must also be willing to entertain models in which the 

 permeant is only loosely associated with a carrier which shuttles or rotates 

 back and forth. The latter models, indeed, would better fit the possibility 

 that organic compounds and inorganic ions are transported by similar 

 systems. For these several reasons the writer prefers, instead of "permease", 

 the less committal term "transport system". 



In closing, I would like to list some of the problems concerned with 

 permeability that now press for analysis at a molecular level. What is the 

 structure of transport systems, and how are the specific carrier proteins 

 related to the lipid in these differentiated portions of the membrane ? What 

 is the mechanism of the energetic coupling required for active transport ? 

 Does it involve change in the structure of the permeant (more than simply 

 reversible adsorption), or change in the structure (and hence affinity) of the 

 carrier, or still another process that will have to be described in as yet 

 unknown terms ? Does a system capable of active transport become un- 

 coupled from energy expenditure when transporting downhill rather than 

 uphill ? Is the same polypeptide chain, differently attached, responsible for 

 the specificity of a transport system and that of an enzyme acting on the 

 same compound ? What accounts for the fact that exchange of external 

 and internal permeant is faster than net transport : does a loaded ferryboat 

 shuttle faster than an empty one ? How do compounds normally imperme- 

 able from the outside become readily excreted by mutants blocked after 

 them ? How much does the non-specific "leakiness" of membranes vary 

 with physiological state, and what is its relation to cellular function and 

 to viability ? Is the site of induction of a transport system within the cell ? 

 Or is it at the membrane, as suggested by the fact that citrate can induce a 

 transport system for itself in a cell which is relatively impermeable to it, 

 and which is meanwhile rapidly synthesizing and converting citrate 

 endogenously. 



In a sense, research on transport systems, despite its spurt during the 

 past decade, has been frustrating. Direct chemical attack on simplified 

 systems, extracted from the cell, has been extending the solid march of 



