598 PANTOTHENIC ACID 



j8-alanine with the lactone. An approximately theoretical yield may thus 

 be obtained. This type of condensation has also been carried out with the 

 dry sodium salt of )S-alanine and yields directly the sodium salt of panto- 

 thenic acid. Pantothenic acid has also been obtained by the condensation 

 of the lactone with |8-alanine benzyl ester followed by the catalytic hydro- 

 genation of the pantothenic benzyl ester to free pantothenic acid.^"- ^°' ^^ 



III. Biochemical Systems 



FRITZ LIPMANN 



A. INTRODUCTION 



In 1943 Roger Williams wrote in Advances in Enzymology} "The pre- 

 sumption, in view of the known function of other vitamins, is that panto- 

 thenic acid fits into some enzyme system or systems which is essential to 

 metabolism. What this enzyme system is or what these systems are is not 

 known. There are some facts which suggest that pantothenic acid may be 

 concerned with carbohydrate metabolism, but it is not certain." 



At that time, other than a slight connection between carbohydrate 

 storage and pantothenic acid,^ found in Dr. Williams' laboratory, there 

 existed only one promising observation, namely, a demonstration of a 

 specific stimulation of pyruvic acid oxidation by pantothenic acid in Proteus 

 morgani by Dorfman et at} in this country, and independently by Hills* 

 in England. However, this observation remained an isolated fact for several 

 years. 



In 1946, during the study of the acetylation of sulfonamide in cell-free 

 systems of pigeon liver, Lipmann^- ® observed that a coenzyme was in- 

 volved in this reaction, which could not be replaced by any of the then 

 known coenzymes. Independently, in the study of acetylcholine synthesis 

 in brain extracts, Feldberg and Mann^ and Nachmansohn and Behrman^ 

 found that for acetylation of choline a stable cofactor seemed necessary. 

 In view of the indication that a novel factor may be involved in acetylation 

 reactions, an isolation of the coenzyme was started and after preliminary 

 purification it was shown, as illustrated by Fig. 1, that the cof actors for 



1 R. J. Williams, Advances in Enzymol. 3, 253 (1943). 



2 R. J. Williams, W. A. Mosher, and E. Rohrmann, Biochem. J. 30, 2036 (1936). 



3 A. Dorfman, S. Berlman, and S. A. Koser, /. Biol. Chem. 144, 393 (1942). 

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



6 F. Lipmann, J. Biol. Chem. 160, 173 (1945). 



^ F. Lipmann and N. O. Kaplan, Federation Proc. 5, 145 (1946). 



7 W. Feldberg and T. Mann, J. Physiol. 104, 411 (1946). 



8 D. Nachmansohn and M. Behrman, /. Biol. Chem. 165, 551 (1946). 



I 



