ALIPHATIC ORGANIC ACIDS 147 



We may visualize a metabolic pool of any given acid, with carbon 

 flowing into it from a high level of carbohydrate and flowing out into 

 amino acids, into respiratory carbon dioxide, and into other undeter- 

 mined channels. Under conditions of minimal demand on the pool 

 for growth, the accumulation of acid is determined by the available 

 carbohydrate, by the relative rates of the many reactions which pro- 

 duce and break down the acid, and by the rate of exchange of acid 

 between cell and environment. The scheme of Figure 1, applying 

 specifically to citric acid, is in principle a model for all acid accumula- 

 tion. An acid may be more closely related to carbohydrate, as is 

 gluconic acid, or it may be in a metabolic "shunt" removed by one or 

 more enzymatic steps from the main pathway of carbohydrate dis- 

 similation. 



Physiologically, a utilizable acid serves as a reserve carbon source, 

 although the concept is more or less meaningless under the usual con- 

 ditions of acid accumulation in culture. A priori, it would appear that 

 the soluble acids, having effects on both the pH and the osmotic con- 

 centration of the medium, are less satisfactory reserve substances than 

 the insoluble polysaccharides and fats. 



The permeability of the cell membrane to organic acids deserves 

 more study, difficult as the problem is. Obviously, a biochemical 

 equilibrium will be reached very quickly within the cell, and very little 

 acid will accumulate, if the formed acid cannot leave the cell. If it 

 leaves rapidly, in fact, the concept of enzymatic equilibrium becomes 

 almost inapplicable. Conversely, if re-entrance of external acid into 

 the cell is slow, its utilization as a source of carbon will be limited. 

 It is conceivable that some of the environmental factors which favor 

 acid accumulation act primarily on the rate of exchange between 

 cell and environment, and that differences between strains reflect mem- 

 brane differences rather than enzymatic capabilities. 



The genetic factor is so far a matter of observation only — acid forma- 

 tion is highly specific and individual strains differ from each other 

 both quantitatively and qualitatively. These strain differences must 

 not, however, be overemphasized; so far only one instance of complete 

 loss of ability to form an acid has been reported, that of Aspergillus 

 fumaricus (p. 141), and even the altered strain is able under some 

 conditions to form the missing product. Quantitative changes are 

 frequent, especially when several acids compete for carbon. The 

 qualitative constancy is particularly remarkable in view of the fact 

 that in many of the fungi studied for acid production the conidia 

 used for transfer of cultures represent isolations of nuclei from a 

 heterocaryotic mycelium. 



