630 J. M. REINER 
ably all the other proteins increase), and then begins to increase and exert the kind 
of control over further synthesis that we have studied in the preceding section. 
Crude as the model may be, it is suggestive. 
The essence of these cases 1s that, under conditions of competition or interaction, 
it is no longer necessary for all proteins to rise or fall together, nor is it necessary 
that they rise uniformly or fall uniformly. And (despite the practical difficulties, at 
the moment, of working out the whole system in all its glory) it is worth stressing 
again that the composition of all the interacting proteins, as well as the relative 
availability of their templates, will largely determine who does what and with which 
and to whom. 
DISCUSSION 
Perhaps more than any of you, | am conscious of the shortcomings of what has been 
presented above, of the issues omitted, the mathematical difficulties glossed over or 
only partly solved. I do not feel that the development is at a stage where it can be 
deemed to lead to critical tests of the mechanisms assumed. I do believe that it illus- 
trates the nature of the problems to be solved in the kinetic analysis of such systems, 
and the kind of algebraic debris that besets the path to a solution. I hope that some 
of the results presented will also have some intrinsic interest or at the very least 
some heuristic value. 
The problems of amino acid uptake and pool sizes are too important to be con- 
sidered as casual incidents of a kinetic analysis. I have therefore taken a relatively 
simple view of the matter, for the sake of getting something done, since others are 
treating these problems in greater depth. One thing might well be pointed out: the 
considerations that led Dr. BritreN to his more complex mechanism of transport 
and pool size determination are very relevant to the kinds of data he is talking about; 
but they do not altogether vitiate our simpler approach to another set of problems. 
The reversible internal binding of amino acids in the cell serves, from our point of 
view, as a sort of buffer mechanism or reservoir for available amino acids to be 
used in synthesis. The simple permease mechanism will give the wrong answers for 
pool sizes and the details of exchange reactions; but I do not believe that it seriously 
falsifies the issues of synthesis. It is not difficult to show, for the BRITTEN model, 
that the rate of the first step of protein synthesis (e.g., amino acid activation) in the 
steady state is equal to the rate of the transport step (carrier or permease) and in- 
dependent of the properties of the internal binding system. 
We have given only a cursory treatment of the problems of growth. Among items 
deserving analysis in the future are three obvious ones: (a) the fact that quantities 
like the 7; and 7; will not be constant in a growing system, but will increase in a 
way that will depend on another set of permeases (e.g., for the purine and pyrimidine 
bases and their precursors); (b) the changes in cell volumes and surfaces that occur 
in growing systems, their mechanisms (e.g., osmotic water uptake balancing internal 
synthesis of macromolecules), and their effect on transport (the surface-volume 
ratio is involved in the equations for transport from extracellular to intracellular 
phase, though this point was ignored in our treatment) ; (c) the relations between mass 
increase and division in growing systems. The third problem has been considered 
extensively by RASHEvsky!™, whose ingenious analysis should be brought up to 
date biochemically and adequately tested. A possible approach to some aspects of 
References p. 632 
