CHAIRMAN'S INTRODUCTION 575 



Studies on kinetics involve not only rates of transport but steady-state 

 levels. In the recent work on uptake by bacteria of the non-metabolized 

 /S-galactoside TMG (^-methylthio-D-galactoside) it has been shown that 

 the levels reached in active transport, at various concentrations of perm- 

 eant, appear to depend on a steady state between entrance by a specific 

 pump and exit by difi^usion, or at least by a system exhibiting the linear 

 concentration relations of difi^usion [7, 8]. 



4. Competition 



Studies with radioactive compounds in animal cells and in bacteria 

 have shown that certain structurally related permeants (e.g. similar amino 

 acids such as isoleucine and valine) interfere with each other's entry, in 

 terms both of rate and of final level reached. This finding is incompatible 

 with difiusion through pores, but consistent with either entrv via a common 

 carrier or adsorption to common intracellular sites. With /S-galactosides in 

 bacteria, it has been possible by further competition studies to choose 

 between these two mechanisms [7, 8]. The active transport system for 

 /S-galactosides exhibits both ditferent Alichaelis constants and diff"erent 

 rates of transport for various members of this class of compounds. When 

 the cells are in equilibrium with permeant A the addition of B, with higher 

 affinity and slower transport than A, displaces several molecules of A per 

 molecule of B taken up. This finding fits competition for a transport 

 system but would be difficult to reconcile with competition for intracellular 

 binding sites. 



This competition has clarified certain obscure cases of analogue 

 inhibition. Analogues of metabolites, such as the sulphonamide drugs, 

 have generally been considered to inhibit growth by competing with the 

 corresponding metabolite at an enzyme site. However, some analogues, 

 notably of amino acids, interfere with exogenously added metabolite but 

 not with the same metabolite endogenously formed. Thus arginine 

 inhibits the growth of mutants that require lysine but not of the parent 

 strain, which synthesizes its own lysine. The prolonged blindness of non- 

 specialists to permeability problems is illustrated by the fact that this 

 lysine-arginine problem perplexed all of us interested in microbial mutants 

 for a decade, until Alathieson and Catcheside [9] suggested the now 

 obvious explanation and supported it with evidence that arginine inter- 

 fered with lysine uptake. 



5. Mutation 



A novel contribution of studies on bacteria was the finding that the 

 formation of a specific transport system, like that of an enzyme, was under 

 the control of a corresponding gene. Suggestions in this direction arose 

 from explorations of biosynthetic pathways with auxotrophic mutants, 



