LIPID STORAGE UNDER ABNORMAL CONDITIONS t>»<5 



pantothenic acid is a component in the coenzyme A molecule, which is 

 apparently necessary for the synthesis of fat. For a further discussion of 

 the relationship of coenzyme A to fat synthesis, the reader is referred to 

 Chapter II, Volume III. 



d'. Nicotinic Acid Fatty Livers: Fatty livers may occur on low-fat, 

 choline-free diets, in association with either a deficiency or an excess of 

 nicotinic acid. The mechanism of the action is completely different under 

 these two conditions. Thus, Salmon 623 reported that, on low-fat, lipogenic 

 diets containing less than 18% of casein, a nicotinic acid deficiency was pres- 

 ent; this was counteracted by a high level (30%) of dietary fat. This 

 effect is believed to be due to the nicotinic acid-sparing action ensuing when 

 the energy metabolism is shifted from carbohydrate to fat. 



On the other hand, a number of workers have demonstrated the liver- 

 fattening action of diets high in nicotinic acid. Handler and Dann 860 

 found that the inclusion of nicotinic acid in the diets of rats on a low casein 

 diet, at a 1% level, resulted in the production of fatty livers, although it did 

 not inhibit growth. However, when nicotinic acid was present in the diet 

 at a 2% level, a slight inhibition of growth was noted. Niacinamide, when 

 incorporated in the diet in a 1% proportion, almost completely inhibited 

 growth. The fatty liver formation could be prevented by the administra- 

 tion of methionine, or by that of choline and homocystine, but not by cho- 

 line, betaine, homocystine, or cystine alone. Foa et al. m confirmed the 

 lipogenic action of nicotinic acid and of nicotinamide reported by Handler 

 and Dann, and demonstrated that these vitamins likewise increased the 

 severity of hemorrhagic degeneration of the kidneys. Both effects were 

 reversed by choline. 



A number of workers 862-864 had previously shown that the excess nico- 

 tinic acid or nicotinamide is excreted by rats, dogs, and man in the urine as 

 trigonelline. The reaction is pictured in (5). On the basis of these facts, 

 Handler and Dann 860 explained their results by showing that nicotinamide 

 had removed the available methyl groups in the trigonelline molecule, and 

 thus had deprived the body of the ability to form choline. When an ade- 

 quate excess of methyl groups was available, the fatty livers did not occur. 

 It is thus evident that neither excess nor deficiency of nicotinic acid per se can 

 be considered to be the causative factor in fatty infiltration of the liver. 



860 P. Handler and W. J. Dann, /. Biol. Chem., llfi, 357-368 (1942). 



861 P. P. Foa, N. L. Foa, and H. Field, Jr., Arch. Biochem., 6, 215-224 (1945). 



862 J. W. Huff and W. A. Perlzweig, J. Biol. Chem., 142, 401-416 (1942). 



863 H. P. Sarett, /. Nutrition, 23, 35-45 (1942). 



864 H. P. Sarett, J. W. Huff, and W. A. Perlzweig, J. Nutrition, 23, 23-34 (1941). 



