670 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



It was found that the edematous condition of the animals on the choline- 

 free diet was associated with fatty infiltration and cirrhosis of the liver. 



k'. The Effect of Excessive Doses of Choline and of Methionine : Luecke 

 and Pearson 781 found that the daily administration of 40 g. of choline chlo- 

 ride to dogs and to sheep, over a period of six days, did not increase the 

 free or total choline content of the liver, kidney, or plasma. The choline 

 was apparently metabolized, inasmuch as only 0.7 to 2.5% of that fed could 

 be recovered in the urine of the sheep, and only 0.5% in that of the dog. 

 The urine nitrogen was increased by an amount equivalent to that of the 

 choline nitrogen ingested. The mechanism by which this large amount of 

 choline is destroyed is problematical. Handler and Bernheim 782 demon- 

 strated that the activity of choline oxidase is depressed in the case of the 

 fatty liver. Luecke and Pearson 781 postulate that a reverse mechanism 

 may be set up, and that the feeding of large quantities of choline stimulates 

 the activity of this enzyme, thereby preventing any increase in the choline 

 content of the tissues or of the blood. 



In contradistinction to the lack of toxicity of massive doses of choline, 

 methionine may have a harmful effect if given in large amounts. Roth and 

 Allison 783 demonstrated that, when 4.8% of methionine was added to a diet 

 containing 12% of casein, a marked loss of weight occurred in the case of 

 the rats. This represents the fat stores of the animal. In later work, Roth 

 and Allison 784 reported that the injury caused by a diet containing 4.8% 

 methionine was aggravated when choline was omitted from the diet. 

 Under these conditions, atrophy of the seminal vesicles was also observed. 

 When the dietary methionine was increased to 7%, the excretion of cre- 

 atinine was augmented, and marked hypertrophy of the kidney occurred. 

 This suggests that the catabolism of methionine or of homocysteine requires 

 the simultaneous catabolism of fat. 



(6) Fatty Livers Resulting from, a Deficiency of Lipocaic. a'. Experi- 

 mental Evidence of Lipocaic in Tests on Dogs: After the early work of 

 Hershey, 572 in which it was found that raw pancreas prevented the de- 

 velopment of fatty livers in depancreatized dogs, it was at first generally 

 accepted that this effect could be traced to the lecithin or choline content of 

 the gland. The first view opposing this explanation was that of Ralli, 

 Flaum, and Banta, 785 who indicated that the pancreas exerted a more bene- 

 ficial effect in controlling liver lipid than could be accounted for on the 



781 R. W. Luecke and P. B. Pearson, J. Biol. Chem., 158, 561-566 (1945). 



782 P. Handler and F. Bernheim, /. Biol. Chem., 144, 401-403 (1942). 



783 J. S. Roth and J. B. Allison, Proc. Soc. Exptl. Biol. Med., 70, 327-330 (1949). 



784 J. S. Roth and J. B. Allison, /. Biol. Chem., 183, 173-178 (1950). 



786 E. P. Ralli, G. Flaum, and R. Banta, Am. J. Physiol, 110, 545-551 (1935). 



