THE ROLE OF DIMETHYL- AND MONOMETHYLAMINO- ETHANOL IN TRANSMETHYLATION REACTIONS IN v1vo*

An investigation of the metabolic behavior of dimethyland monomethylaminoethanol was undertaken as a further study of members of the general class of N-methyl compounds. l It was hoped, however, that in the study of these particular compounds some clue might be uncovered as to the mechanism by which choline is synthesized and degraded in the course of participating in transmethylation reactions (1, 2). In our first exploratory experiments, the growth-promoting properties of both monomethyland dimethylaminoethanol were studied. The monomethyl compound proved to be so toxic that its activity could not be adequately tested. In addition to the growth studies on dimethylaminoethanol, data were also obtained on its effect on fatty livers and hemorrhagic kidneys. Finally, the labeling of the methyl groups with deuterium was resorted to in order to gain a closer insight into the fate of the methyl groups of these compounds. After the feeding of the labeled compounds, the tissue choline and tissue creatine were isolated and their deuterium content was determined. For the preparation of deuteriomonomethylaminoethanol, deuteriomethyl iodide, prepared from deuteriomethyl alcohol (l), was used as the methylating agent of N-p-toluenesulfonylaminoethanol. For the preparation of deuteriodimethylaminoethanol, direct methylation with deuteriomethyl iodide could not be employed.’ Therefore, advantage was taken of the procedure of Clarke, Gillespie, and Weisshaus (4) for the methylation of amines with formic acid and formaldehyde. Deuterioformic acid, obtained by pyrolysis of deuteriooxalic acid (5), was used with ordinary formaIdehyde to methyIate aminoethanol. In this way, the methyl group is labeled by the partial replacement of 1 hydrogen atom by deuterium. This synthesis has the advantage of using a readily available source of the