394 VIII. CHOLESTEROL AND RELATED STEROLS 



poi'ted an increased incorporation of deuterium into the cholesterol mole- 

 cule in thyroxine-injected rats as compared with normal controls. This 

 increase was noted in the liver, intestine, kidneys, and spleen, but not in the 

 lungs. Spirtes, Medes, and Weinhouse'^^^ likewise recorded augmented 

 cholesterol sjoithesis under these conditions, and stated that it was not di- 

 rectly correlated with the glycogen content of the liver; these variations 

 were observed in spite of the fact that the oxidation of acetate was increased 

 30 to 60% in the hyperthyroid condition. Both groups of workers observed 

 that the reverse situation obtained in regard to cholesterol synthesis in 

 thyroidectomized animals. -^--'^^ Stresses such as that produced by lower- 

 ing the environmental temperature by 20 to 28 °C. did not alter the rate of 

 cholesterol synthesis in the athyroid rats.^^^ 



Although the pancreas is essential in the synthesis of fatty acids from ace- 

 tate, this organ is not required for the acetate — *■ cholesterol reaction. 

 Thus, although liver slices from alloxanized rats and from pancreatecto- 

 mized cats are relatively ineffective in provoking the acetate — »• fatty acid 

 reaction, in contrast to liver slices from normal rats and cats, Brady and 

 Gurin-^^ reported that the acetate — »■ cholesterol reaction is unimpaired. 

 However, this latter reaction may be inhibited in prolonged and severe 

 diabetes. On the other hand, Hotta and Chaikoff^*^ have suggested that 

 cholesterol synthesis from acetate is actually increased in the liver of dia- 

 betic rats. In a later study from their laboratory, Hotta and co-workers-^^ 

 made the interesting observation that the rate of cholesterol synthesis 

 from acetate in the liver of the alloxanized diabetic rat was double that of 

 normal rats when both groups were fed a diet containing 60% glucose. 

 However, the rate of cholesterogenesis of these rats was reduced to normal 

 if fructose replaced glucose in the diet. It is assumed that the restoration 

 of glycolytic activity in the diabetic liver induced by fructose was responsi- 

 ble for diverting the C2 fragment from the path of cholesterol sjaithesis to 

 other metabolic pathways, such as lipogenesis. Altman and collabora- 

 tors-" observed that cortisone and insulin, when acting concomitantly, 

 exerted a marked effect upon fatty acid synthesis, without affecting that 

 of cholesterol. All experimental evidence indicates the independence of 

 the lipogenic and the cholesterogenic reactions. 



^^' M. A. Spirtes, G. Medes, and S. Weinhouse, XlXth Intern. PhysioL Congress, Abst., 

 Montreal, Aug. 31-Sept. 3, 1953, pp. 789-790. 



264 R. O. Brady and S. Gurin, /. Biol. Chem., 187, 589-596 (1950). 

 2" S. Hotta and I. L. Chaikoff, /. Biol. Chem., 198, 895-899 (1952). 



266 S. Hotta, R. Hill, and I. L. Chaikoff, /. Biol. Chem., 206, 835-844 (1954). 



267 K. I. Altman, L. L. Miller, and C. G. Bly, Arch. Biochem. Biophys., 31, 329-331 

 (1951). 



