d4 II. BIOSYNTHESIS 



acetoacetyl-CoA which, in turn, is cleaved into two molecules of acetyl- 

 CoA. Coon and co-workers^^** have proposed a mechanism for the syn- 

 thesis of acetoacetate and its breakdown in heart muscle. 



(6) The Role of Hormones in the Biosynthesis of Fat 



a. The Effect of Insulin. Insuhn has a profound effect on the rate of 

 synthesis of fat. Although the extent of lipogenesis from acetate in rat 

 liver slices was increased several times when pyruvate was added to the 

 substrate, Bloch and Kramer^* reported that it was still further augmented 

 when insuhn was also introduced into the medium. These results are 

 interpreted as indicatmg that msuhn must be concerned with the utilization 

 of pyruvate for the synthesis of fatty acids. The addition of glucose or 

 oxaloacetate augmented fat synthesis from acetate to a somewhat lesser 

 degree than did pyruvate. When insulin was added to a glucose-containing 

 medium, increased lipogenesis also occurred. 



Although Brady and Gurin^^ reported that the addition of insulin to a 

 medium containing acetate increased the rate of its incorporation into long- 

 chain fatty acids, no increased Hpogenesis from acetate was caused by this 

 hormone if glucose was absent. Masri et at. ^^^ noted that insulin by itself 

 was inactive in promoting lipogenesis from acetate in liver shces obtained 

 from rats which had fasted for eighteen hours. Haugaard and Stadie^^^ 

 confirmed the stimulatory effect of crystalline insulin on the incorporation 

 of acetate into the hver fatty acids of the rat. 



The quantitative aspects of the insuhn effect have been recorded by 

 Felts, Chaikoff, and Osborn.^^^ It was found that only 2% of the acetate 

 became incorporated into the fatty acids in surviving liver shces from 

 alloxan-diabetic rats. On the other hand, when these slices were treated 

 with insuhn, the incorporation of C^^ from acetate into the fatty acids was 

 found to range between 6 and 23%. Conversely, the oxidation of acetate 

 was also markedly reduced in hver slices from insulin-treated rats. The 

 diabetic liver was found to oxidize two to four times as much of the car- 

 boxyl-carbon of acetate as it did of the methyl carbon. The introduction 

 of insulin reduced the oxidation of formate-C^^ to C^^02, and concomi- 

 tantly increased its incorporation into fatty acids. However, the actual 

 amounts of formate-C^* isolated as fatty acids were quite small. Balmain 



"' M. J. Coon, J. R. Stern, A. del Campillo, and S. Ochoa, Federation Proc, 12, 191 

 (1953). 



160 M. S. Masri, I. Lyon, and I. L. Chaikoff, /. Biol. Chem., 197, 621-624 (1952). 



1" E. S. Haugaard and W. C. Stadie, J. Biol. Chem., 200, 753-757 (1953). 



1" J. M. Felts, I. L. Chaikoff, and M. J. Osborn, J. Biol. Chem., 193, 557-562 (1951). 



