86 CHOLINE 



for the growth of an Escherichia coli mutant (No. 113-3), a form which 

 requires either B12 or methionine.'"^ The growth-promoting value of homo- 

 cysteine was enhanced by a trace of B12, by a methyl donor such 

 as dimethyl-j8-propiothetin, or by catalytic amounts of p-aminobenzoic 

 acid. Dubnoff suggested that B12 is necessary for the maintenance of homo- 

 cysteine in the reduced state and that it may also be required for the syn- 

 thesis of 7)-aminobenzoic acid which may be involved in the synthesis of 

 methyl groups. According to Shive, p-aminobenzoic acid, folic acid, and B12 

 are involved in the metabolism of formate in microorganisms.^^" Ling and 

 Chow reported that B12 corrected the decreased sulfhydryl content of blood 

 of Bi2-deficient rats.^" 



Although the dog has been used in most of the investigations on lipocaic, 

 believed by Dragstedt to be a pancreatic hormonal anti-fatty liver f actor, ^^^ 

 studies on rats also have been conducted and with varying results. Data 

 have been presented which support the view that the lipotropic activity 

 of preparations of lipocaic is explained completely by their content of cho- 

 line and of protein. ^^^'^^^ In contrast to these results are findings which indi- 

 cate that the potency of lipocaic cannot be explained on the basis of its 

 content of choline, methionine, or inositol .^"'^^^ More recently, successful 

 ligation of the pancreatic duct has been reported to result in fatty livers 

 in rats on a choline-deficient diet.-^- As in the experiments on dogs to be 

 discussed later, this result appears due to the lack of a proteolytic factor 

 in the external secretion of the pancreas that normally releases a choline 

 precursor, presumably methionine, from dietary protein. Choline and the 

 anti-fatty liver factor of the pancreas were reported to have opposing effects 

 on the excretion of urinary ketones. ^-^ 



Rats fed a protein-free diet showed an accumulation of liver glycogen 

 and fat after one month, and the increase in lipid was only partially pre- 



2»3 J. W. Dubnoff, Arch. Biochem. and Biophys. 37, 37 (1952). 



210 W. Shive, Ann. N. Y. Acad. Sci. 52, 1272 (1950). 



211 C.-T. Ling and B. F. Chow, Federation Proc. 11, 249 (1952). 



212 L. R. Dragstedt, /. Am. Med. Assoc. 114, 29 (1940); 115, 454 (1940). 



213 F. X. Aylward and L. E. Holt, Jr., /. Biol. Chem. 121, 61 (1937). 



21* E. M. MacKay and R. H. Barnes, Proc. Soc. Exptl. Biol. Med. 38, 410 (1938). 



215 C. H. Best and J. H. Ridout, Am. J. Phijsiol. 122, 67 (1938). 



216 A. N. Wick and E. Laurence, Arch. Biochem. 20, 113 (1949). 



2" H. J. Channon, J. V. Loach, and G. R. Tristram, Biochem. J. 32, 1332 (1938). 



218 G. Gavin, J. M. Patterson, and E. W. McHenry, J. Biol. Chem. 148, 275 (1943). 



219 D. E. Clark, M. L. Eilert, and L. R. Dragstedt, Am. J. Physiol. 144, 620 (1945). 



220 M. L. Eilert and L. R. Dragstedt, Am. J. Physiol. 147, 346 (1946). 



221 M. J. Raymond and C. R. Treadwell, Proc. Soc. Exptl. Biol. Med. 70, 43 (1949). 



222 G. H. A. Clowes, Jr. and L. B. Macpherson, Am. J. Physiol. 165, 628 (1951). 



223 V. Baccari and A. Guerritore, Boll. soc. Hal. biol. sper. 24, 842 (1948). 



