KONRAU BLOCII 



a-carbon atom. McKay pcrspicaciously suggested that valeric acid 

 and other odd-numbered fatty acids yield, on oxidation, /3-keto acids 

 which then undergo hydrolysis to acetic acid. Condensation of two 

 acetic units would then give rise to acetoacetate. 



By employing fatty acids labeled with deuterium and C^', it 

 has been possible to provide more direct support for the principle of 

 beta oxidation and to establish that acetic acid is the source of the 

 "extra" ketone bodies. The first experiment bearing on the question 

 of degradation by elimination of C2 units was carried out by Schoen- 

 heimer and Rittenberg (19) who demonstrated the biological conver- 

 sion of deuteriostearic acid to deuteriopalmitic acid. It was clear 

 from their data that this transformation was direct and not attributable 

 to utilization of smaller fragments derived from stearic acid. Ana- 

 lytical data for the myristic and lauric acid fractions indicated that the 

 process of C2 removal did not end at the Cie stage. It is noteworthy 

 that the fatty acids with carbon chains longer than Cio are constituents 

 of tissue fat but appear to be metabolically inert when added to tissue 

 slices or tissue extracts, whereas the lower acids from C2 to Cg are 

 oxidized in vitro but cannot be detected in tissue fat. Evidently the 

 rate of oxidative breakdown increases with decreasing chain length, 

 both in vitro and in vivo. Actually, the lower fatty acids may arise in 

 considerable quantities in the animal body over an extended period of 

 time, but their concentration in the stationary state is insignificant be- 

 cause they are rapidly oxidized further. Evidence supporting this 

 concept has been secured in the case of acetic acid. This acid should 

 be the principal intermediate which is formed by hydrolytic splitting 

 of the ^-keto acids in the course of beta oxidation. Although isolation 

 of this compound might be achieved by working up large quantities 

 of animal tissues or urine, its normal concentration in tissues and body 

 fluids is apparently too small to permit ready identification. 



An investigation with the aid of deuterioacetic acid of the way 

 in which foreign amines are acetylated revealed that acetic acid is 

 utilized directly in the acetylation reaction (1,5). The excreted acetyl 

 compound contains only a fraction of the isotope present in the dietary 

 acetic acid; dilution of the isotope by acetic acid arising in inter- 

 mediary metabolism must have occurred in the tissues. If the de- 

 crease in isotope content occurring in the acetylation reaction could be 

 ascribed exclusively to the presence of endogenous acetic acid, then the 



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