Biosynthesis of Cholesterol 23 



at a normal rate, it has become clear that the pituitary 

 secretes a principle which is capable of inhibiting hepatic 

 synthesis of fat. Preliminary results indicate that purified 

 growth hormone is at least one of the factors responsible for 

 this inhibition (Brady, Lukens and Gurin, 19516). Cortisone 

 is also effective in this respect. 



Since the diabetic liver is characterized by an accelerated 

 oxidation of fattv acids to two-carbon fragments, which can 

 no longer be reconverted to fatty acids, these fragments must 

 accumulate or be diverted into other metabolic pathways. 

 In as much as both acetoacetate and two-carbon fragments 

 are utilized in the biosynthesis of cholesterol, it is perhaps 

 not surprising that hypercholesterolaemia is so prominent a 

 feature of the diabetic state. 



Although it is generally believed that acetoacetate is 

 primarily synthesized in liver (and to a minor extent in 

 kidney), the evidence that acetoacetate may be required for 

 the biosynthesis of cholesterol implies that all tissues capable 

 of synthesizing cholesterol under in vitro conditions must 

 have an obligatory synthetic mechanism for the production 

 of acetoacetate. We have recently found this to be true for 

 testicular (rabbit) and adrenal (human) tissue. Incubation 

 of either of these tissues with radioactive acetate in the 

 presence of carrier non-radioactive acetoacetate results in the 

 formation of acetoacetate containing a significant proportion 

 of the administered ^^C. It is of interest that Jowett and 

 Quastel (1935) were able to demonstrate a net synthesis of 

 acetoacetate in testis. Whether this will prove to be true for 

 all other tissues capable of synthesizing cholesterol must 

 await further experimentation. 



REFERENCES 



Bloch, K. (1948). Cold Spr. Harb. Sym. quant. Biol., 13, 29. 

 Block, K., Borek, E., and Rittenberg, D. (1946). J. biol. Chem.y 



162, 441. 

 Borek, E., and Rittenberg, D. (1949). J. biol. Chem., 179, 843. 

 Brady, R. O., and Gurin, S. (1950a). J. biol. Chem., 186, 461. 

 Brady, R. O., and Gurin, S. (19506). J. biol. Chem., 187, 589. 



