32 II. BIOSYNTHESIS 



sumably synthesized by the bacteria. Moreover, Brown and SnelP" pre- 

 pared a large number of synthetic compounds with LBF activity, as meas- 

 ured by Lactobacillus helveticus 80 (present in Swiss cheese), by treating 

 pantethine with sodium sulfide, cysteine, glutathione, and several thiols. 



Numerous derivatives of CoA exist in which the sulfur is in reduced form. 

 In addition to the combination of CoA with the acetyl group, there are 

 combinations with various fatty acids (propionyl, butyryl, and other acyl 

 groups), with dicarboxylic acids (succinyl) and with the acetoacetyl group. 

 Wakil and Mahler^^^-^^^ and Kornberg and Pricer''*^'^*^ proved that the 

 linkage of the higher fatty acids with CoA is analogous to that between 

 the acetyl group and CoA. 



Pantethine is the name for the oxidized form of CoA which may be repre- 

 sented as CoAS-SCoA. It is not active until present in the reduced form. 

 Any of several mixed disulfides may exist. 



d. Reactions of the Thiol Group of Coenzyme A. The thiol or mer- 

 captan group is the functional part of the CoA molecule, just as it is in 

 the case of cysteine or in reduced glutathione. Most of the studies on this 

 group have been carried out with acetyl-CoA, which gives the typical reac- 

 tions of acetyl mercaptans. Thus, acetyl-CoA obtained in partially puri- 

 fied form from yeast^"-^*" was shown to give a color reaction with sodium 

 nitroprusside which is characteristic of an acetyl mercaptan.^'*^ Acetyl- 

 CoA also exhibits lability toward mercury salts ;^'' this is another character- 

 istic of an acetyl mercaptan. However, the — SH group is protected 

 by the acetate group when acetyl-CoA is exposed to iodoacetate.^^- The 

 latter compound has a destructive effect on the unprotected — SH group. 

 After mild hydrolysis of the acetyl-CoA, which results in the liberation of 

 the — SH group, the coenzyme loses its power to catalyze the acetylation 

 of sulfanilamide.'''*' 



e. The Distribution of Coenzyme A. Coenzyme A was first prepared 

 from liver, and this tissue is the most reliable source of the coenzyme. 

 However, Kaplan and Lipmann^^ have shown that it is widely distributed 

 in animal tissues in microorganisms, and in higher plants. One of the main 

 sources of this co-factor is yeast. ^^ Novelli and Lipmann*^*^** demon- 

 strated that yeast can synthesize CoA from pantothenic acid when the 



1" G. M. Brown and E. E. Snell, Proc. Soc. Exptl. Biol. Med., 77, 138-140 (1951). 



"8 S. Wakil and H. R. Mahler, Federation Proc, 12, 285 (1953). 



139 H. R. Mahler, S. J. Wakil, and R. M. Bock, /. Biol. Chem., 204, 453-468 (1953). 



i« A. Kornberg and W. E. Pricer, Jr., /. Am. Chem. Soc, 74, 1617 (1952). 



1" A. Kornberg and W. E. Pricer, Jr., /. Biol. Chem., 204, 329-343 (1953). 



"2 F. Lynen, Ann., 574, 33-37 (1951 ). 



i« G. D. Novelli and F. Lipmann, J. Biol. Chem., 171, 833-834 (1947). 



