CHOLINE 



13. FUNCTION OF CHOLINE 



Reference has already been made to the prevention and cure of 

 fatty livers in rats by administration of choline, betaine or methionine 

 and to the fact that the compounds are not completely biologically 

 equivalent. 



Before discussing the part that choline plays in the economy of the 

 animal body, it is necessary to examine more closely the relationship 

 between choline, betaine and methionine. 



Methionine 



Methionine is a sulphur-containing amino acid with the formula (I) . 



CHgS . CH2 . CH2 . CH . COOH HS . CH^ . CH2 . CH . COOH 



I I 



NH2 NH2 



(I) (11) 



HS.CH2.CH COOH 



(HI) 



Like choline, it has the property of preventing fatty liver forma- 

 tion in rats fed a high fat, low choline diet.^ This property was 

 not possessed by its demethyl derivative, homocysteine (II), the 

 higher homologue of cysteine (HI),^ and this striking difference 

 indicated that the lipotropic action of methionine was probably 

 associated with the labile methyl group. This was confirmed, and 

 additional light thrown on the connection between methionine and 

 choline, when W. C. Rose and E. E. Rice ^ showed that homocysteine 

 was lipotropic when given at the same time as tiki tiki or a milk 

 concentrate to supply the vitamin B complex. It was inferred from 

 this that these supplements contained an unknown factor necessary 

 for the methylation of homocysteine. Du Vigneaud et al.^ showed 

 that the factor was choline {a) by acetylating the concentrates and 

 demonstrating pharmacologically the presence of acetylcholine ; 

 {b) by actually isolating choline as the reineckate ; and (c) by showing 

 that homocysteine and choline chloride produced the same increase 

 in weight as methionine and also — ^what is more significant perhaps — 

 prevented the formation of fatty livers in precisely the same way as 

 methionine. They therefore concluded that one of the functions of 

 the methyl group of methionine was to make possible the synthesis 

 of choline in the body. 



In order to obtain direct evidence in support of this hypothesis 

 methionine in which the hydrogen atoms of the methyl group had been 

 replaced by deuteriimi atoms was fed to rats maintained on a diet 



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