KONRAD BLOCK 



and the fact that palmitic acid is in biological equilibrium with cetyl 

 alcohol (23), may be of significance. 



In testing experimentally the hypothesis of C2 condensation, the 

 choice among compounds containing two carbon atoms is rather 

 limited. Except in the case of the amino acid glycine, the existence of 

 C2 compounds in animal tissues has never been substantiated by 

 isolation. Acetic acid suggests itself as a likely intermediate if only for 

 the reason that it arises as a product of fatty acid degradation. When 

 acetic acid containing deuterium in sufficient concentration to induce 

 detectable deuteriocholesterol formation was administered to rats, no 

 significant amounts of isotope appeared in the fatty acids (4). But 

 when the experiment was repeated with an acetate preparation contain- 

 ing very high concentrations of deuterium as well as a carboxyl group 

 labeled with C^^, the fatty acids of liver and depot were found to 

 contain both isotopic carbon and deuterium (16). The incorpora- 

 tion of both isotopes proved that the acetate molecule had been utilized 

 as such. However, the ratio of the concentrations of the two isotopes 

 in the fatty acids synthesized differed considerably from that in the fed 

 material, indicating that the conversion involved a loss of carbon- 

 bound hydrogen. Lability of the hydrogen atoms in the methyl group 

 of acetic acid cannot be responsible, since the ratio of the two isotopes 

 remains unchanged when acetic acid is employed in the acetylation of 

 foreign amines (unpublished results of Bloch and Rittenberg). It 

 follows that the intermediates in the fatty acid synthesis are of such a 

 nature as to permit loss of carbon-bound deuterium by exchanging it 

 with the hydrogen of the body fluids. An analogous conclusion was 

 necessary with respect to the intermediates in fatty acid oxidation. 

 The failure to detect fatty acid synthesis from acetate labeled by 

 deuterium alone and in relatively low concentrations, emphasizes the 

 caution which is necessary in the interpretation of negative data. 

 Use of a test compound containing the stable isotope of carbon as well 

 as deuterium not only eliminates the uncertainty arising from hydrogen 

 lability but also permits certain deductions from the change of the 

 D:Ci3 ratio. 



The mechanism of condensation leading to the structure of 

 cholesterol must differ in at least some respects from that in\ olved in 

 fatty acid synthesis. Owing to the complexity of the chemical struc- 

 ture of cholesterol the nature of the condensation reactions has re- 



302 



