BIOSYNTHESIS OF CHOLESTEROL 395 



According to Tomkins, Chaikoff, and Bennett, ^^^ the rate of cholesterol 

 synthesis from acetate in the liver is markedly reduced in hypophysecto- 

 mized rats. It is suggested that the pituitary gland controls the rate of 

 steroid production in non-endocrine as well as in endocrine target organs. 



i. The Effect of Vitamin Deficiencies, (a) Pantothenic Acid De- 

 ficiency. Deficiencies, particularly of the B vitamins, have been found to 

 influence cholesterol synthesis. Because pantothenic acid is a structural 

 unit of CoA, it is only natural to expect that a deficiency of this vitamin 

 would alter cholesterol metabolism, presumably by hmiting the extent of 

 cholesterogenesis. In support of this hypothesis, Guehring, Hurley, and 

 Morgan-^^ noted that the increase in liver lipids and in liver and serum 

 cholesterol was much less pronounced in pantothenic acid-deficient rats 

 receiving 1% cholesterol than in normal animals. These effects were not 

 related to curtailment of food intake. Winters et al^^° likewise observed 

 the failure of rats deficient in pantothenic acid to develop fatty livers. Al- 

 though the serum cholesterol was found to be normal in these animals, a 

 marked reduction in total cholesterol was noted in the "resting state" 

 after the deficient diet had been fed for five or six weeks. Although the 

 level of ascorbic acid in the adrenal gland was not reduced in pantothenic 

 acid deficiency, -^^ the cholesterol content of these endocrine glands was 

 shown to be decreased. ^^^ The latter effect is believed to be the result of a 

 depressed synthesis of this sterol in the adrenal glands, rather than to aug- 

 mented utilization. This decreased synthetic capacity is obviously the re- 

 sult of the reduced content of CoA available. Dumm and co-workers^^' 

 likewise reported that adrenal cholesterol is significantly depressed in 

 pantothenic acid-deficient rats, as compared with control rats on a normal 

 diet. Moreover, it was demonstrated that, following unilateral adrenalec- 

 tomy, the cholesterol content of the remaining adrenal gland returned to 

 normal in a single day if the rat had been on a complete diet, but that the 

 content was still low in this gland seven days after the operation when the 

 rat had received a diet free from pantothenic acid. Klein and Lipmann^^^ 

 observed a parallelism between the level of CoA and the synthesis of choles- 

 terol in the livers of pantothenic acid-deficient rats. When the anti- 



268 G. M. Tomkins, I. L. Chaikoff, and L. L. Bennett, /. Biol. Chem., 199, 543-545 

 (1952). 



259 R. R. Guehring, L. S. Hurley, and A. F. Morgan, /. Biol. Chem., 197, 485-493 

 (1952). 



2«» R. W. Winters, R. B. Schultz, and W. A. Krehl, Proc. Soc. Exptl. Biol. Med., 79, 

 695-696(1952). 



261 M. E. Dumm, H. Gershberg, E. M. Beck, and E. P. RaUi, Proc. Soc. Eiptl. Biol. 

 Med., 82, 659-662(1953). 



262 H. P. Klein and F. Lipmann, /. Biol. Chem., 203, 101-108 (1953). 



