28 CHOLINE 



ments. The conversion of carbon 2 of histidine into choline methyls, pre- 

 sumably by way of formate, is supported by the finding of Soucy and 

 Bouthillier^"^ that approximately one-fourth of the radioactivity of an hy- 

 drolyzate of liver protein svas in the form of serine after feeding rats labeled 

 histidine. The reverse reaction, the synthesis of histidine from precursors 

 that include formate, has been demonstrated by Coon and Levy.^^^' i""* 

 These observations are not unexpected in view of the earlier discovery by 

 Edlbacher^"^' ^^^ of the enzyme, histidase, in liver and its disruption of the 

 imidazole ring to give a product yielding formate on acid hydrolysis. 



It is significant that satisfactory proof is lacking for a methyl donor 

 function for mono- and dimethylaminoethanol.** As in the case of the re- 

 ported transmethylation of methyl from sarcosine,^''^ unequivocal proof 

 would require double labeling of the methyl to rule out intermediary 

 formate formation, i.e., oxidation and reduction of the carbon in question. 

 Du Vigneaud^'** has shown that deuterium-methyl-labeled dimethylamino- 

 ethanol is converted in the rat into choline. This final methylation, yield- 

 ing choline, is apparently an irreversible reaction, inasmuch as Muntz^"^ 

 found dimethylglycine rather than dimethylaminoethanol after the incu- 

 bation of rat liver homogenate with added choline and homocysteine. Sub- 

 stantial support for the conclusion that oxidation of choline to betaine 

 is necessary before transmethylation occurs is provided by the observa- 

 tions of Dubnoff"" and others on choline oxidase (Section IV, p. 33). 



The methylation m vivo of homocysteine, following its administration 

 as such or as homocystine, is discussed in Section IV, p. 19. Similarly, the 

 reciuirement of methionine in chicks is satisfied by homocystine plus 

 choline'" or betaine."^ These metabolic reactions undoubtedly spare the 

 requirement of methionine, and there is no reason to doubt that the methio- 

 nine-homocysteine reaction may account for repeated transfers of intact 

 methyl. Nevertheless, it is pertinent to emphasize the fact that homo- 

 cysteine and its disulfide form are not known to occur naturally and that 

 their presence in the body is dependent on the methionine intake except in 



102 R. Soucy and L. P. Bouthillier, Rev. can. biol. 10, 290 (1951). 



"^ M. J. Coon and L. Levy, Federation Proc. 10, 174 (1951). 



10^ L. Levy and M. J. Coon, J. Biol. Chem. 192, 807 (1951). 



">5 s. Edlbacher and J. Kraus, Hoppe-Seyler's Z. physiol. Chem. 191, 225 (1930); 195, 



267 (1931). 

 106 S. Edlbacher, Ergeh. Enztjmforsch. 9, 131 (1943). 

 10' V. du Vigneaud, S. Simmonds, and M. Cohn, /. Biol. Chem. 166, 47 (1946). 



108 V. du Vigneaud, J. P. Chandler, S. Simmonds, A. W. Moyer, and M. Cohn, J. Biol. 

 Chem. 164, 603 (1946). 



109 J. A. Muntz, J. Biol. Chem. 182, 489 (1950). 



110 J. W. Dubnoff, Arch. Biochem. 24, 251 (1949). 



111 A. A. Klose and H. J. Almquist, /. Biol. Chem. 138, 467 (1941). 



112 H. J. Almquist and C. R. Grau, J. Nutrition 27, 263 (1944). 



