III. BIOCHEMICAL SYSTEM 617 



Carbohydrate Fat 



i i 



Pyruvate Acetoacetate 



Two Carbon Fragment 

 C'Acetate") 



Cholesterol «- 



Steroid Hormones <- 



Hemin <- 



Fatty Acids <- 



-» Citric Acid 

 -> Glutamic Acid 

 -> Proline 

 -> Arginine 



Fig. 7. Synthetic products derived from the 2-carbon fragment. 



phosphate, led to the formulation of the enzyme-catalyzed process as 

 essentially the conversion of acetyl phosphate to acetyl-CoA by an equi- 

 libration reaction; this observation furnished definite evidence for the 

 existence of acetyl-CoA and its identity with "active" acetate. ''^ This was 

 further substantiated by the interchangeability of a great variety of donor 

 systems to donate acetyl by way of CoA to the sulfanilamide acetyl-ac- 

 ceptor enzyme.^^' ^^' ^'^' ^^ It was shown that acetyl phosphate, through 

 phosphotransacetylase,^^ pyruvate,^^' ®^ and, furthermore, the ATP-CoA- 

 acetate reaction of animal tissues and of yeast could furnish a common 

 acetyl donor, acetyl-CoA, for the same acceptor system. ^^' ^^- ^^ 



The just-mentioned ATP-CoA-acetate reaction represents one of the 

 most important acetyl donor reactions in animal tissues. Its mechanism 

 remained for a long time obscure. It recently was clarified through the 

 work of Lipmann et alJ^ The reaction was found unexpectedly to yield in- 

 organic pyrophosphate according to an over-all reaction: 



CoA + acetate + ATP ;^ Acetyl CoA + AMP -f pyrophosphate 



The reaction is freely reversible.'^''" The finer mechanism of the reaction was 

 recently further clarified through use of isotope exchange reactions by 

 Jones ei alJ^^ 



Integrating the reactions just discussed, we are led to the construction 

 of what may be called a general acetyl transfer field, separated into donor 



68 J. R. Stern, B. Shapiro, E. R. Stadtman, and S. Ochoa, /. Biol. Chem. 193, 703 



(1951). 

 6^ S. Korkes, A. Del Campillo, I. C. Gunsalus, and S. Ochoa, J. Biol. Chem. 193, 



721 (1951). 

 '0 F. Lipmann, M. E. Jones, S. Black, and R. M. Flynn, J. Am. Chem. Soc. 74, 2384 



(1952). 

 70o M. p]. Jones, S. Black, R. M. Flynn, and F. Lipmann, Biochim. et Biophijs. Acta 



12, 141 (1953) ; M. E. Jones, Federation Proc. 12, 708 (1953). 

 ""' M. E. Jones, F. Lipmann, H. Hilz, and F. Lynen, J. Am. Chem. Soc. 75, 3285 (1953) . 



