SATURATED FATTY ACIDS 21 



CoA is apparently the active component of the liver extract. Monguio^^ 

 and MacKay et al.^^ obtained similar data with ordinaiy acetate in the in- 

 tact or fasting animal, while Swendseid and associates,^^ using C^^-acetate, 

 also reported acetoacetate synthesis in fasting animals. 



When octanoic acid containing a C^^-labeled carboxyl group was fed, 

 Weinhouse and associates'^ found a considerable amount of C'^ present in 

 the carbonyl group of the acetoacetate. This would indicate that the 

 octanoic acid was degraded into two-carbon units which would again be 

 combined in a random manner to form acetoacetate. The following two 

 possibilities niight explain the results: 



CH3-(CH2)6-Ci300H > 4C.. > 2CH3-C130-CH2-C1300H (1) 



CH3-(CH2)6-C"OOH > C,'^ + C2 + CH3-CH2-CH2-COOH (2) 



CH3 • CH2 • CH2 • COOH > CH3 • CO • CH2 • COOH 



C2I3 4- 0.13 > CH3-C"0-CH2C"OOH 



According to reaction (1), all the acetoacetate would be of synthetic origin 

 while, wdth reaction (2), the acetoacetate would be a mixture of "primary" 

 (non-synthetic) and synthetic acetoacetate molecules. The four terminal 

 carbon atoms would be a direct source of acetoacetate. However, in 

 later studies with carboxyl-labeled butyric acid, Medes et al.^^ noted an 

 unequal distribution of C^^ between the carboxyl and the carbonyl groups 

 of acetoacetate. The acetoacetate could not have been formed by a 

 random combination of two equivalent C2 molecules; it is postulated that 

 the newly formed acetoacetate is in equilibrium with acetate as follows: 



CH3CH2CH2COOH > CH3COCH2COOH , 2CH3COOH (3) 



A similar rapid interconversion of acetoacetate and acetate obtains in 

 the liver^^ and in the kidney,^" but it is not known whether or not the 

 splitting of acetoacetate proceeds rapidly enough to account for a redistri- 

 bution of the isotope as indicated above. Lehninger^^ reported that the 

 reverse reaction proceeds slowly in muscle mince. 



The primary formation of acetoacetate is also indicated in the in vivo 



8U. Monguio, Klin. Wochschr., 31, 1116-1120 (1934). 



«5 E. M. MacKay, R. H. Barnes, H. O. Carne, and A. N. Wick, /. Biol. Chem., 135, 

 157-163 (1940). 



«« M. E. Swendseid, R. H. Barnes, A. Hemingway, and A. O. Nier, /. Biol. Chem., 142, 

 47-52 (1942). 



»'S. Weinhouse, G. Medes, and N. F. Floyd, J. Biol. Chem., 155, 143-151 (1949). 



«« G. Medes, S. Weinhouse, and N. F. Floyd, J. Biol. Chem., 157, 35-41 (1944). 



8' S. Weinhouse, G. Medes, and X. F. Floyd, J. Biol. Chem., 158, 411-419 (1945). 



'"G. Medes, X. F. Flovd, and S. Weinhouse, J. Biol. Chem., 162, 1-9 (1946). 



»i A. L. Lehninger, J. Biol. Chem., US, 147-157 (1942). 



