IX. EFFECTS OF DEFICIENCY 679 



presence of fatty acids in the medium;"^- "^ similarly, the inhibitory effect 

 on these organisms of antivitamins related to pantothenic acid in structure 

 is greatly decreased by addition of free or combined fatt}^ acids to the me- 

 dium.2^^ Pantothenic acid greatly increases the synthesis of acetylcholine 

 by Lactohacillus 'plantarumr^'^ 



Dorfman and coworkers^^^ found that the rate of pyruvate oxidation by 

 cells of Proteus morganii was depressed when the cells were grown with sub- 

 optimal amounts of pantothenic acid; the rate of oxidation was increased 

 by addition of pantothenic acid to the resting cell suspension. Similar obser- 

 vations were made by Hills.^®^ Both authors considered that the vitamin 

 takes part in the oxidation of pyruvic acid to acetic acid. Novelli and Lip- 

 mann^^^ showed that this increased oxidation was mediated by coenzyme A, 

 which is formed almost quantitatively by such organisms from the panto- 

 thenic acid which they take up. This coenzyme is concerned in the initial 

 reactions (condensation of acetate with oxalacetate) leading to the oxidation 

 of acetate.^®^' ^^^ This was shown in striking fashion by the demonstra- 

 tion that acetate accumulated from ethanol in the presence of a pantothenic 

 acid-deficient yeast suspension, but not in the presence of a similar sus- 

 pension rich in pantothenic acid. The latter preparation of cells also re- 

 moved acetate from solution (by oxidation) much more rapidly than the 

 former deficient cells.^^'* 



As a result principally of the work of Lipmann and his group, pantothenic 

 acid is now known to be essential for a whole series of reactions (and possi- 

 bly all reactions) involving the acetyl group. As a preliminary to participa- 

 tion in such reactions, it must be built into its coenzyme form, coenzyme 

 ^263, 266 'pjjQ latter coenzyme, together with various degradation products 

 of it, accounts for essentially all the "bound" pantothenic acid present in 

 tissues. Knowledge of these facts permits a ready explanation of most of 

 the metabolic effects described above. Thus, coenzyme A is required for 

 formation of fatty acids from acetate, and hence the addition of preformed 

 fatty acids in a form directly utilizable for cell synthesis might be expected 

 to decrease the pantothenic acid requirement of organisms such as L. 



253 H. P. Broquist, Ph.D. Thesis, University of Wisconsin, 1950. 



259 W. Shive, W. W. Ackermann, J. M. Ravel, and J. E. Sutherland, /. Am. Chem. Soc. 



69, 2567 (1947). 

 "0 E. Rowett, J. Gen. Microbiol. 2, 25 (1948). 



"1 A. Dorfman, S. Berkman, and S. A. Koser, /. Biol. Chem. 144, 393 (1942). 

 "2 G. M. Hills, Biochem. J. 37, 418 (1943). 

 263 G. D. Novelli and F. Lipmann, J. Bacteriol. 54, 19 (1947); Arch. Biochem. 14, 23 



(1947). 

 2" G. D. Novelli and F. Lipmann, /. Biol. Chem. 171, 833 (1947). 

 2" J. R. Stern, B. Shapiro, and S. Ochoa, Nature 166, 403 (1950). 

 26« G. D. Novelli, N. O. Kaplan, and F. Lipmann, J. Biol. Chem. 177, 97 (1949). 



