Biosynthesis of Cholesterol 



21 



with CO2 to form acetoacetate (Coon, 1950) and can, in 

 addition, be cleaved to two-carbon fragments, it is not sur- 

 prising that the intact animal can readily utilize the terminal 

 carbon atoms of iso valerate for the biosynthesis of cholesterol. 

 Preliminary experiments with labelled vinylacetic acid 

 indicate a limited incorporation, while aldol is utilized about 

 as well as acetoacetate. In contrast to aldol, ^*C labelled 

 crotonic aldehyde contributes no carbon atoms to cholesterol 

 under these experimental conditions. Liver slices are more- 

 over unable to utilize labelled formate or formaldehyde for 

 this biosynthesis (Table IV). 



Table IV 

 Biosynthesis of Cholesterol by Liver Slices 



Exp. 

 No. 



1 

 2 



3 



4 



Substrate 



CHgi^COONa 



CHgi^COOXa 



14CH3I4CHOH14CH2CHO 



CHgi^COONa 



H^^COOXa 

 CHgi^COONa 



Radioactivity 



Recovered as 



Cholesterol 



cpmlmg. C* 



20, 29 

 303, 265 

 33, 

 795, 450 

 178 

 570 

 30, 

 

 950 



Substrate 

 Incorporate 



0-3, 

 4-2, 3- 

 0-7, 



3, 4' 







3 



0-4, 

 

 8-8 



♦Each pair of results represents a separate experiment with an acetate control. 



For the time being, any theories concerning the mechanism 

 of biosynthesis of cholesterol must be based upon the utiliza- 

 tion of acetate or acetaldehyde, acetoacetate, and metabolites 

 which can be derived from these substances. Although it is 

 attractive to speculate about three-carbon or one-carbon 

 precursors there is no supporting evidence in their favour. 

 Pyruvate is poorly utilized in the in vitro system while acetone 

 apparently goes through a two-carbon intermediate. The 

 ready incorporation of the isopropyl fragment of isovalerate 



