THE TRANSFER OF THE METHYL GROUP FROM METHIONINE TO CHOLINE AND CREATINE

Abstract

We have recently shown that homocystine (homocysteine) can replace methionine in the diet of the white rat only in the presence of choline or certain related substances," 2 and have suggested that choline enables the animal to synthesize methionine under these conditions.It was postulated that the fundamental process involved is a transfer of a methyl group from the nitrogen of choline to the sulfur of homocysteine.Furthermore it was suggested that the reaction might be reversible and thus methionine might act as a donor of methyl groups in the synthesis of choline in the body.It was realized that direct proof of the transfer of the methyl group (transmethylation) was highly desirable.We decided to attempt first to trace the migration of the methyl group from methionine to choline.A methionine was therefore synthesized containing deuterium in the methyl group.The trideuteromethyl iodide used in the synthesis3 was prepared from deuteromethyl alcohol, which had been made by reduction of CO with Dz by the method of Zanetti.4The trideuteromethionine (23.9 atom per cent D) was fed at an average daily rate of 70 mg.(2.4 mg. of deuterium) for 3 weeks to rats kept on a methionine-choline-free diet.The choline chloroplatinates isolated from the tissues contained 32.2 and 31.7 atom per cent deuterium respectively, repre-