82 CHOLINE 



the relation of thiamine to the synthesis of fat, it is doubtful if the deposi- 

 tion of extra fat resulting from the supplementation of the deficient diet 

 has any different explanation from that which explains satisfactorily the 

 effects of biotin,"^ cystine/ and minerals. ^''^ This conclusion is given solid 

 support by the findings of Boxer and Stetten, who caused labeling of newly 

 synthesized fat by the administration of D2O in rats, produced fatty livers 

 on a low choline diet with and without dietary thiamine, and noted that 

 the decrease in the synthesis of fat in the thiamine-deficient animals was 

 paralleled by that in the animals supplied thiamine but restricted to the 

 same food intake as the thiamine-deficient group. "^ 



By way of contrast to thiamine, it is of interest that pyridoxine has been 

 reported to be necessary for the prevention of fatty livers. Rats deficient 

 in vitamin Be developed fatty livers to a greater extent than controls,^'''' 

 and necrosis of the kidney cortex was noted more frequently as a symptom 

 of choline deficiency."^ The feeding of a very high casein diet after depletion 

 of fat and of B vitamins resulted in an additional weight loss and in the 

 development of fatty livers unless pyridoxine was supplied."^ According to 

 Engel, pyridoxine and essential fatty acids must be present for the normal 

 functioning of choline as a lipotropic agent in rats.^^- 



Niacin and its derivatives have been linked with lipotropism in rats in a 

 variety of experiments. Niacinamide and, under certain conditions, the di- 

 phosphopyridine nucleotide inhibited choline oxidase in in vitro studies. '^^ 

 Growth of rats on low protein, methyl-poor diets containing niacinamide 

 was affected adversely, presumably because of further depletion of methyl 

 due to the formation and excretion of N^-methylniacinamide.^^ The cystine 

 effect was absent in young rats unless nicotinic acid was present in the 

 diet,^*^ and the cystine effect was abolished in older animals in the presence 

 of generously adequate levels of this vitamin. ^^^ Forbes found that the addi- 

 tion of niacin to a low choline diet increased the cholesterol content of 

 fatty livers and decreased the responsiveness of the animals to the lipotropic 

 effect of choline. ^^^ It is not possible to conclude that any of these effects 

 represent direct relations between the metabolism of choline and of niacin 

 in vivo except the changes introduced by the methylation of the vitamin. 

 Many of these results may be explicable on the basis of non-specific effects 

 on food intake and utilization* Handler showed that dietary niacinamide 

 (2 %) resulted in a greater loss of weight in partially hepatectomized rats 



1" G. E. Boxer and D. Stetten, Jr., /. Biol. Chem. 153, 607 (1944). 



1" N. Halliday, J. Nutn'tion 16, 285 (1938). 



'■'s P. Gyorgy and R. E. Eckardt, Biochem. J. 34, 1143 (1940). 



"9 E. W. McHenry and G. Gavin, /. Biol. Chem. 338, 471 (1941). 



IS" J. N. Williams, Jr., G. Litwack, and C. A. Elvehjem, /. Biol. Chem. 192, 73 (1951). 



181 J. C. Forbes, J. Nutrition 22, 359 (1941). 



