COENZYMES DERIVED FROM B VITAMINS 191 



active phosphorylated acetate (prepared enzymatically from acetic acid 

 and adenosine triphosphate by dried bacterial cells) has been reported. 251 

 It contains equimolecular amounts of reactive acetyl and phosphoryl 

 groups; hence, it is not acetyl pyrophosphate. In an acidic environment 

 (pH 1.5) the "active acetate" spontaneously undergoes a transformation 

 producing a compound which is indistinguishable from synthetic acetyl 

 phosphate. 251 To distinguish the biologically active compound from acetyl 

 phosphate the former will be referred to as the reactive -phosphoryl- acetyl 

 intermediate. 



Origin of the Reactive Phosphoryl-Acetyl Intermediate. The reactive 

 acetyl compound is formed during carbohydrate metabolism by the oxida- 

 tive phosphorylative decarboxylation of pyruvic acid which is catalyzed 

 by thiamine pyrophosphate (p. 162). It seems logical that this is also 

 the compound formed during jatty acid (and sterol?) degradation when 

 the C2 fragments are successively cleaved from the molecule. It probably 

 is the intermediate formed from ketogenic amino acids when they are 

 catabolized. Substances metabolically related to fatty acids — acetoacetic 

 acid and ethanol — undoubtedly are metabolized via metabolic pathway 

 in which the reactive acetyl intermediate occurs. It has been shown that 

 the tricarboxylic acids can be cleaved to yield oxalacetic acid and the 

 reactive acetyl molecule by a reversal of the reactions in which these 

 acids are formed. 241 When an exogenous supply of acetic acid is available, 

 cells can use a pantothenic acid enzyme, "acetylphosphorylase," to 

 "activate" the acetic acid molecule; adenosine triphosphate is the phos- 

 phorylating agent. 



The Coenzyme Derived from Pantothenic Acid 



Ten years elapsed between the time (1936) that pantothenic acid was 

 first found to participate in carbohydrate metabolism 253 and the time 

 that the mechanism of its function was established. 



Physiologists interested in nerve metabolism discovered (in 1942) an 

 enzyme system in brain tissue which was responsible for the synthesis 

 of acetylcholine from acetic acid, choline, and adenosine triphosphate. 254 

 At about the same time another group of investigators demonstrated the 

 presence in liver of an enzyme which converts sulfonamides and other 

 aromatic amines into the less toxic amides by acetylation. 249 They showed 

 that the preparations contained a heat-stable, dissociable component 

 which would reactivate enzyme systems which had been inactivated by 

 dialysis. This coenzyme was subsequently shown to be a necessary com- 

 ponent of the system which acetylated choline. 255 



Initial attempts to demonstrate the presence of a B vitamin in this 

 coenzyme were unsuccessful, because pantothenic acid, the essential vita- 



