INTERMEDIARY METABOLISM 



acetic acid must be considered a potential source of ketone bodies. * 

 The ketogenic action of «-valcric acid, which has also been shown to 

 yield acetic acid in the normal animal (5), can be readily explained as 

 resulting from the condensation of two molecules of acetate. 



In liver tissue in vitro, the oxidation of fatty acids appears to lead 

 to acetoacetic rather than to acetic acid as an end product. Since 

 such experiments are performed with slices from fasted animals, the 

 accumulation of ketone bodies may well be related to the lack of 

 carbohydrate or carbohydrate intermediates, conditions which, in the 

 intact animal, result in ketosis. It would be unwarranted to conclude 

 that in the normal, well-nourished animal the acetic acid formed by 

 fat breakdown necessarily condenses to acetoacetate prior to its further 

 oxidation. It is equally conceivable that normally fat oxidation takes 

 the course visualized by Knoop and that the acetate-acetoacetate 

 condensation goes into effect only when the catabolism of acetic acid 

 is interfered with. 



Fatty Acid Synthesis 



It is well recognized that fat can be synthesized from carbo- 

 hydrate, but information as to the chemical nature of the process is 

 totally lacking. Any proposed mechanism must be in accord with 

 the fact that the component fatty acids of tissue fat without exception 

 have an even number of carbon atoms and comprise all members of 

 the series up to C20 and higher. The simplest general scheme for the 

 biosynthesis of all fatty acids would be one involving building units 

 containing two carbon atoms. Proof of C2 condensation has been 

 established in at least one case by the finding that deuteriopalmitic 

 acid is converted to deuteriostearic acid by the rat (22). Since 

 deuteriostearic acid is also degraded biologically to deuteriopalmitic 

 acid, the reversible removal and addition of C2 units is clearly a normal 

 event. As to the nature of the fatty acid derivative undergoing the 

 chain elongation, the natural occurrence of fatty acid aldehydes 



* In this connection, the question a.s to whether pyruvic acid can be con- 

 verted to acetic acid in vivo needs further investigation. From our findings witii 

 deuterioalanine, which we used as a source of deuteriopyruvic acid, it appears that 

 pyruvate-acetate conversion in the liver constitutes only a minor pathway for 

 pyruvate metabolism. 



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