PANTOTHENIC ACID 



i8. PANTOTHENIC ACID ANALOGUES 



Pantothenic Acid and its Derivatives 



It has already been stated (page 354) that L-pantothenic acid is 

 inactive on bacteria/ rats and chicks. ^ Simple derivatives of D-panto- 

 thenic acid generally exhibited activity when tested on rats, but not 

 on micro-organisms. For example, the acetate,^ benzoate ^ and di- 

 phosphate * were active on rats, but inactive on bacteria, and ethyl 

 monoacetyl-pantothenate ^' * and ethyl pantothenate ^> ® were as 

 effective as an equivalent amount of calcium pantothenate in pro- 

 moting the growth of pantothenic acid deficient rats and chicks, but 

 stimulated the growth of L. helveticus only slightly. Pantothenic 

 acid ^-nitrobenzoate was also inactive when tested microbiologically.^ 

 Apparently the rat and presumably other mammals are able to convert 

 such derivatives, which are not available to the organism per se, into 

 the free vitamin. 



A. L. Neal and F. M. Strong '^ found that pantothenic acid in liver, 

 yeast, cheese and eggs was accompanied by as much as half its equiv- 

 alent of an alkali-stable substance utilised by L. helveticus with the 

 same degree of efficiency as pantothenic acid and by chicks four times 

 as efficiently ; this substance has not been adequately characterised, 

 but it is believed to be a substitution product of pantothenic acid. 



(^-Alanine and Related Compounds 



As has already been pointed out (page 361), ^-alanine can serve as 

 a growth factor for certain species of yeast, ®» ^ certain strains of 

 C. diphtheriae ^^' ^^ and, to a certain extent apparently, for rats.^^» ^^ 

 Micro-organisms that can thus utilise ^-alanine have been shown to 

 convert it into pantothenic acid ^> ^^ (page 387). 



a-Methyl-j8-alanine had only o-ooo6 of the activity of j8-alanine 

 towards the Gebriider-Mayer strain of bakers' yeast, and partially 

 antagonised the growth-promoting effect of jS-aJanine.^* Isoserine and 

 ^-aminobutyric acid also antagonised the action of ^-alanine on yeast.^^ 



Analogues Derived from ^-Alanine 



'Most of the analogues synthesised in the course of elucidating the 

 structure of pantothenic acid showed less than i % of the activity 

 of pantothenic acid, or none at all, when tested on micro-organisms. 

 These compounds included a8-dihydroxyvaleryl-^-alanine,^®'^^»^® ay-di- 

 hydroxyvaleryl-/3-alanine,i^' ^^ ay-dihydroxybutyryl-j8-alanine,^^ ay-di- 

 hydroxy-^-methylbutyryl-j3-alanine,i^ ay-dihydroxy-a-methylbutyryl- 

 jS-alanine, ajSy-trihydroxy-butyryl-jS-alanine^® and ae-dihydroxy- 

 caproyl-/3-alanine.^® 



Mitchell et al}^ found only one substance, the so-called " hydroxy- 



394 



