LIPIDE METABOLISM 



461 



the amount of this compound picscnt in blood and body tissues. 

 Therefore it is qiute evident that cholesterol must be synthesized in 

 the animal body. 



Biosynthesis of Cholesterol 



It has been established that all the carbons of cholesterol synthesized 

 in the animal can be obtained from a common source, acetyl CoA. 

 Although the liver is the site of the majority of cholesterol synthesis 

 in vivo, it has been shown that this compound can be produced by a 

 large variety of tissues. Moreover, many tissues, including liver, 

 adrenal cortex, and arterial wall, are capable of stimulating the 

 production of cholesterol iii vitro. The use of such tissues in vitro 

 shows that the cholesterol molecule can also be synthesized from 

 acetoacetic acid, apparently without prior degradation to a C2 unit. 



Whatever the starting material, acetyl CoA, acetoacetic acid, or 

 isovaleric acid, it is agreed that the formation of cholesterol proceeds 

 through the condensation of acetyl groups to form an isoprenoid unit, 

 which in turn serves as the skeletal material for the production of the 

 hydrocarbon, squalene. Probably the first product of cyclization (ring 

 formation) is lanosterol. At this point the hydroxyl group which ap- 



CH3COOH 



\ 



c— c— c 



isoprenoid unit 

 (sec page 202) 



lanosterol 



squalene 



zymoslerol 



cholesterol 



