62 II. BIOSYNTHESIS 



intestine of the intact rat after phlorhizin had been injected in a single 65 

 mg. dose. This finding was confirmed by Stillman and Fries (cited by 

 Chaikoff^^^), who used much larger doses of the drug. Moreover, DiLuzio 

 and Zilversmit^^^ found no change in the liver phospholipid of the phlo- 

 rhizinized dog, in spite of the fact that the level of plasma phospholipids 

 was elevated. The turnover of phospholipids in the liver and plasma was 

 increased over that of the controls. These observations support the 

 conclusion that phlorhizin does not inhibit the incorporation of phosphate 

 into the phospholipid molecule in the intact animal. On the other hand, 

 according to Taurog (cited by Chaikoff^^^), phlorhizin reduced the extent 

 of incorporation of P*' into the phospholipids of surviving liver slices. 



e. The Effect of Pancreatectomy. After the removal of the pancreas, 

 a marked stimulation of the rate of phospholipid synthesis obtains in the 

 plasma. Harper and co-workers*^* observed an increase in the rate of turn- 

 over of plasma phosphohpids in diabetic dogs after the feeding of raw 

 pancreas. However, Chaikoff et al.^^^ reported that no change in the rate 

 of phospholipid turnover in depancreatized dogs occurred after insulin had 

 been withdrawn, provided that the level of blood phospholipid remained 

 constant. In later work, Zilversmit and DiLuzio* ^^ noted a marked in- 

 crease in phospholipid synthesis in the liver and plasma of depancreatized 

 dogs; slightly smaller increases of phospholipid synthesis were observed in 

 the kidney and small intestine. The variation in rate of synthesis of phos- 

 pholipid was only slight, or absent, in the muscle of diabetic dogs while, in 

 the bram, the new formation of phospholipids proceeded at an identical 

 rate in normal and in depancreatized dogs.*^^ These results are interpreted 

 as indicating that phospholipids are involved in the increased fat metabo- 

 lism in the diabetic dog. 



f. The Effect of Lipotropic Agents and of Related Compounds. The 

 ability of certain compounds to prevent the accumulation of fat in the liver 

 is believed to be related to their stimulating effect upon phospholipid 

 synthesis. Substances which increase the total amount of available cho- 

 line are especially active in augmenting the rate of synthesis of phospho- 

 lipids. Thus, it has been shown that choline itself, ^^^ betaine,*^^ and 

 methionine,*" all of which are potent lipotropic agents, stimulate phos- 



312 N. R. DiLuzio and D. B. Zilversmit, Am. J. Physiol., 170, 472-476 (1952). 



"3 P. V. Harper, Jr., W. B. Neal, Jr., and G. R. Rogers, Proc. Soc. Exptl. Biol. Med., 68 

 363-369 (1948). 



314 1. L. Chaikoff, D. B. Zilversmit, and C. Entenman, Proc. Soc. Exptl. Biol. Med., 68, 

 6-9 (1948). 



315 D. B. Zilversmit and N. T. DiLuzio, /. Biol. Chem., 194, 673-683 (1952). 



316 1. Perlman and I. L. Chaikoff, /. Biol. Chem., ISO, 593-600 (1939). 



3" I. Perlman, N. StiUman, and I. L. Chaikoff, /. Biol. Chem., 133, 651-659 (1940). 



