104 Perspectives in Microbiology 



sent an enormous advance in economy and efficiency of 

 metabolic reactions. An acetyl group is derivable from a 

 variety of sources; but once an acetyl, its origin is no 

 longer apparent, and the acetyl on its carrier may be in 

 equilibrium with a variety of substances — such as fatty 

 acids, citrate, amino acids, and acetate; then when an 

 acetyl group is needed, it must be much simpler for the 

 organism to draw upon the common supply of acetyl than 

 to synthesize it de novo for each separate requirement. It 

 is therefore curious, and I believe significant, that the prin- 

 ciple of group transfer occurs in even the smallest and 

 presumably the simplest, in the sense of the most primi- 

 tive, cells. 



The second characteristic pattern of the metabolic path- 

 ways as found in living cells is the organization into fixed 

 order reaction sequences. A substance A is transformed to 

 substance B, from here on it must go from B to C, from 

 C to D, etc., until it emerges as substance X or Y or Z. 

 But once it is started along the path, its subsequent fate 

 is determined for the next five or ten or perhaps even 

 twenty transformations. As an example, an acetyl group 

 on coenzyme A has before it an array of pathways, but 

 once it has condensed with oxalacetate to form citrate, its 

 subsequent fate is to a considerable extent determined. 

 What else can happen to citrate but conversion to cis- 

 aconitate, then isocitrate, then oxalosuccinate, then a-keto- 

 glutarate? Even at a-ketoglutarate there are only a few al- 

 ternatives, and beyond, half of the acetyl is already lost. 



Such fixed order reaction sequences abound in the living 

 cell. Some are cyclic, some are not, but organization into 

 cycles is not a necessary part of the characteristic sequence. 

 Our present picture is that such paths are tubes or con- 

 duits, rigidly confined. They are turnpikes or Autohahns, 

 not byways or country lanes. In this respect, the word 

 "pathway" is not exactly suitable, since "pathway" con- 

 notes a somewhat wandering way, not set in steel or con- 



