Metabolic Pafhways 105 



Crete, capable of easy branching and alteration as circum- 

 stances require. But so far as I am able to judge, the meta- 

 bolic pathways of the living cell are rigid and enclosed. 

 The plasticity characteristic of life, and the adaptive abili- 

 ties, are more a matter of substituting pathways, and com- 

 petition between them, than a matter of alteration in a 

 fixed order reaction sequence. I admit that this too-rigid 

 mechanistic view is not a very satisfying one, but I am 

 afraid it is correct. In the long view, it is not surprising; 

 after all, the mechanics of muscular movement in our 

 bodies have not changed for at least 10,000 years. Why 

 expect even more fundamental mechanisms, those of chem- 

 ical transformations, or energy release, to be any more 

 fluid? 



These pathways are usually so constructed that they are 

 self-limiting. I suppose the engineer would call these feed- 

 back mechanisms. The word itself has no particular mean- 

 ing to me, and I prefer the term "self-limiting." The 

 Meyerhof-Embden system, for example, requires both 

 adenosine triphosphate (ATP) (at its start) and adenylic 

 acid (beyond the triose phosphate stage), and will stop if 

 all the adenylic is converted into ATP. The same is true 

 for inorganic phosphate. 



In addition, there are ''cyclic" processes — as occur in the 

 citric acid cycle, the urea cycle, the fatty acid cycle, or the 

 choline cycle — and they are all constructed so that the rate 

 at which the cycle proceeds is dependent not only upon 

 substrate, but upon what one might call built-in controls. 

 The element of control in such self-limiting systems is 

 exerted by a second factor, also self-limiting, namely, series 

 or product inhibition. The clearest example is the fact 

 that oxalacetate is one of the most potent inhibitors of 

 succinoxidase known. In the reaction series succinate to 

 fumarate to malate to oxalacetate, the oxalacetate must be 

 removed or the series will stop. In brief, there are, in the 

 fixed series metabolic pathways, two factors of control: 



