SATURATED PATTY ACIDS 33 



solution is aerated in a glucose-phosphate medium. Tissues and micro- 

 organisms which use acetate groups for the synthesis of fatty acids, aceto- 

 acetate, and cholesterol have a much higher content of CoA than do tissues, 

 such as muscle, in which there is little fat synthesis and in which most of 

 the acetate is utilized by way of the tricarboxylic acid cycle. One would 

 expect mammary tissue to be especially high in this component. 



(5) The Role of Enzymes in the Biosynthesis of Fat 



Presumably not only the coenzyme but also an enzyme system is re- 

 quired for fat synthesis. Brady and Gurin'^^ described a preparation 

 from the homogenate of pigeon liver which possessed the ability to cause 

 the incorporation of C^'*-labeled acetate into long-chain fatty acids. In an 

 extension of their earlier work, Brady and Gurin'-*^ have prepared a water- 

 soluble enzyme system from pigeon liver which is capable of effecting this 

 synthesis. This reaction can likewise occur in liver homogenates, as well 

 as in washed mitochondria suspended in particle-free supernatant fluid. 

 The efficiency of the water-soluble system in converting acetate to long- 

 chain fatty acids is approximately equal to that of the homogenate. The 

 synthesis occurs under anaerobic conditions, but the fatty acid oxidation 

 is negligible. In this system, acetyl-CoA appears to be a less efficient 

 precursor of fatty acid than is free acetate. The synthetic process occur- 

 ring under anaerobic conditions is stimulated by Mg++, diphosphopyridine 

 nucleotide (DPN), cytochrome C, and especially by citrate, while Ca"'" + 

 and F~ are inhibitory. 



Bucher^^^ also prepared cell-free homogenates from rat liver which were 

 capable of incorporating labeled acetic acid into long-chain fatty acids and 

 cholesterol. These results have been confirmed by Dituri and Gurin,^'*'^ 

 who also reported that the addition of citrate brought about a twenty-fold 

 increase in lipogenesis. 



Green and co-workers^^^ isolated a soluble enzyme (or a mixture of 

 enzymes) from pig heart muscle which catalyzes a reversible conversion of 

 acetoacetate to acetyl-CoA in the presence of succinyl-CoA. It is sug- 

 gested that the activation of acetoacetate is brought about by a replace- 

 ment reaction with succinyl-CoA, probably leading to the formation of 



i"R. O. Brady and S. Gurin, Arch. Biochem., 34, 221-222 (1951). 

 >« R. O. Bradv and S. Gurin, J. Biol. Chern., 199, 421-431 (1952). 

 1^6 N. L. R. Bucher, /. Am. Chem. Soc, 75, 498 (1953). 

 i"F. Dituri and S. Gurin, Arch. Biochem. Biophys., 43, 231-232 (1953). 

 i« D. E. Green, D. S. Goldman, S. Mii, and H. Beinert, /. Biol. Chem., 202, 137-150 

 (1953). 



