BATURATED FATTY ACIDS 27 



(4) The Role of Coenzyme A in Fat Synthesis 



Reactions which involve the synthesis of fatty acids certainly must en- 

 tail the intermediation of enzymes. CoA has also been identified as a factor 

 important in the transfer of acetyl groups, and hence in fatty acid synthesis. 

 The same co-factor is required for many enzymatic reactions involving C2 

 compounds, which, in addition to acetylation of sulfonamides and choline, 

 includes the synthesis of acetoacetate and citrate, as well as the oxidation 

 of pyruvate and acetaldehyde. In 1945, Lipmann^^ first called attention 

 to the necessity of a soluble co-factor to explain the enzymatic acetylation 

 of sulfanilamide which was effected by pigeon liver extracts. Subse- 

 quently, Lipmann and co-workers^°* were able to obtain a partially puri- 

 fied product containing the active co-factor; this was given the name 

 "coenzyme A" (CoA). 



a. Coenz3nne A in the Transfer of Two-Carbon Intermediates. It 

 is now widely recognized that CoA is able to bring about a dual activation 

 of the acetate molecule. In the transfer of acetyl groups, which is in- 

 volved in condensation reactions such as occur in the synthesis of aceto- 

 acetate, fatty acids, or citrate, the methyl carbon of the acetate is acti- 

 vated. On the other hand, in reactions such as the acetylation of aromatic 

 amines or of choline, CoA activates the carboxyl group of acetate. Lip- 

 man^^'^^ reviewed the role of CoA as understood in 1946, 1948, 1953 and 

 1955,^°* while Ochoa et al.^'^^ summarized the later work on the crystalliza- 

 tion and function of the condensing enzyme. The latter worker has also 

 recorded the unique function of this coenzyme, not only in the mechanisms 

 involved in the transfer of two-carbon units, but also in the activation and 

 transfer of other acyl groups. Other recent reviews on the functional 

 aspects of CoA are those of Stern, ^''''' of Welch and Nichol,^^ and especially 

 that of Lynen.^o 



Acetyl-CoA (active acetate) is a key substance in acetyl transfer. It 

 occupies a central position between the acetyl donor and the acetyl ac- 

 ceptor system; Welch and NichoP^ pictured this relationship as shown in 

 Figure 2, while Lynen et al}^ suggested the intermediate role of acetyl-CoA 

 as illustrated in Figure 3. 



The probability that acetyl-CoA is the intermediate carrier between the 

 acetyl-donor and the acetyl-acceptor systems is strengthened by the 



lo* F. Lipmann, N. O. Kaplan, G. D. Novelli, L. C. Tuttle, and B. M. Guirard, /. Biol. 

 Chem., 167, 869-870 (1947). 



"5 F. Lipmann, Am. Scientist, 43, 37-47 (1955). 



w« S. Ochoa, J. R. Stern, and M. C. Schneider, /. Biol. Chem., 193, 691-702 (1951). 



1" J. R. Stern, Phosphorus Metabolism, 1, 264-271 (1951). 



