ACETIC ACID AND ACETATE 257 



and Bullet,-" it is possible to estimate how much acetate should arise if it is 

 assumed that the fatty acids are the sole cause of acetic acid. The results 

 agree closely with those obtained by the isotope dilution technic* 



One criticism of the use of the isotope dilution method, based upon the 

 concentration of isotopically-labeled acetylamine, for determining the 

 endogenous acetic acid production, is that this may account for only the 

 hepatic acetate. According to Klein and Harris, ^^ the acetylation reaction 

 is confined to the hver, and only the acetate formed outside the liver which 

 escapes oxidation at the site of synthesis may be expected to be included in 

 the hepatic acetate pool. That extrahepatic oxidation of fat takes place 

 is hidicated by meany experimental facts, such as R.Q. studies of hepatecto- 

 mized animals and of heart-lung preparations. For a review of this sub- 

 ject, see page 194. 



(2) Sources of Acetic Acid in the Animal Body 



a. Formation from Even-Chain Fatty Acids. There is very little direct 

 evidence in the literature to substantiate the fact that acetic acid arises in 

 the oxidation of fats. Leloir and Munoz-^ did detect acetic acid in the 

 course of oxidation of octanoate by the liver, but the amounts were insignifi- 

 cant in comparison with the quantity of acetoacetate. Acetoacetate has 

 been demonstrated on feeding the even-chain fatty acids to fasted rats,^*--* 

 and the quantities available per molecule of fatty acids are progressively 

 increased with a lengthening of the carbon chain. Similar results have 

 been reported when fatty acids are metabolized by liver slices.^^"-* These 

 results might indicate that acetoacetate rather than acetate is the final 

 product which orighiates from fatty acids. 



However, a number of experimental facts prove that a two-carbon frag- 

 ment, presumably acetate, is the primary degradation product of fatty 

 acids. For example the change of stearic acid -^ palmitic acid has been 

 demonstrated in vivo unequivocally by Schoenheimer and Rittenberg.^^ 



20 K. Bernhard and F. Bullet, Helv. Chim. Ada, 26, 1185-1189 (1943). 



21 J. R. Klein and J. S. Harris, /. Biol. Chem., 124, 613-626 (1938). 

 " L. F. Leloir and J. M. Munoz, Biochem. J., S3, 734-736 (1939). 



23 H. J. Deuel, Jr., L. F. Hallman, J. S. Butts, and S. Murray, J. Biol. Chem., 116, 

 621-639(1939). 



24 J. S. Butts, C. H. Cutler, L. Hallman, and H. J. Deuel, Jr., /. Biol. Chem., 109, 

 597-613 (1935). 



25 M. Jowett and J. H. Quastel, Biochem. J., 29, 2159-2180 (1935). 



26 P. P. Cohen, /. Biol. Chem., 119, 333-346 (1937). 



27 J. H. Quastel and A. H. M. Wheatlev, Biochem. J., 27, 1753-1762 (1933). 



28 A. L. Lehninger, J. Biol. Chem., 157, 363-381 (1945). 



29 R. Schoenheimer and D. Rittenberg, J. Biol. Chem., 120, 155-165 (1937). 



