626 PANTOTHENIC ACID 



IV. specificity of Action 



SAMUEL LEPKOVSKY 



The activity of pantothenic acid resides only in its dextrorotatory form 

 which has been indicated to be the d configuration by apphcation of Hud- 

 son's amide rule.^~^ l( — )-Pantothenic acid appears to be inactive for 

 organisms requiring the intact vitamin. Pantothenic acid appears to be 

 highly specific and is incapable of modification without loss of activity 

 unless the organisms metabolizing it are capable of regenerating it in vivo} 

 The following are examples which illustrate this. 



1. The methyl and ethyl esters of pantothenic acid are comparable in 

 activity to the vitamin in promoting growth of rats,^- * but ethyl panto- 

 thenate is only about 6.8 % as effective as pantothenic acid for Lactobacillus 

 casei}-^ The rats apparently can hydrolyze the esters in vivo, but the bac- 

 teria cannot. 



2. The alcohol corresponding to pantothenic acid (pantothenyl alcohol) 

 has been found to be effective in animals,^' ^ but it cannot replace panto- 

 thenic acid in the nutrition of lactic acid bacteria and it even inhibits its 

 utilization in these organisms.''^ The utilization of pantothenyl alcohol b,y 

 animals depends upon its in vivo conversion to pantothenic acid. Lactic 

 acid bacteria apparently cannot make this conversion. 



3. Acetylation of pantothenic acid concentrates from natural sources 

 destroys its activity for chicks* and for bacteria.^ However, synthetic ethyl 

 monoacetyl D-pantothenate is as active as pantothenic acid for rats and 

 chicks but is only 0.7 % as effective as the vitamin for Lactobacillus casei}-^ 

 These are impressive examples of the relationship between the potency of a 

 vitamin and the presence of enzyme systems in the organism capable of 

 modifying the vitamin so that it can be metabolized. 



Manj^ analogs of pantothenic acid have been prepared. The /3-alanine 

 has been replaced with other amino acids such as a-alanine, /3-aminobutyric 

 acid, aspartic acid, lysine, and leucine. All such preparations were devoid of 



1 H. C. Park and E. J. Lawson, /. Am. Chem. Soc. 63, 2869 (1941) 



2 C. S. Hudson, J. Am. Chem. Soc. 39, 462 (1917). 



3 R. J. Williams, R. E. Eakin, E. Beerstecher, Jr., and W. Shive, The Biochemistry 

 of the B Vitamins. Reinhold Publishing Corp., New York, 1950. The chapter on 

 pantothenic acid carries an extensive bibliography. 



* K. Unna and C. W. Muschett, Am. J. Physiol. 135, 267 (1942). 



6 S. A. Harris, G. A. Boyack, and K. Folkers, J. Am. Chem. Soc. 63, 2662 (1941). 



6 S. H. Rubin, J. M. Cooperman, M. E. Moore, and J. Scheiner, J. Nutrition 35, 499 

 (1948). 



7 E. E. Snell and W. Shive, J. Biol. Chem. 158, 551 (1945). 



8 D. W. Woolley, H. A. Waisman, O. Mickelsen, and C. A. Elvehjem, J. Biol. Chem. 

 125, 715 (1938). 



9 E. E. Snell, F. M. Strong, and W. H. Peterson, Biochem. J. 31, 1789 (1937). 



