Lipotropic Action of Certain Compounds Related to Choline Chloride. ∗

The hypothesis that choline chloride functions lipotropically by virtue of supplying an essential component of lecithin and possibly other lipid complexes appears particularly worthy of consideration. In this connection many compounds related to choline chloride have been subjected to examination, using the mouse method described in the previous paper. Two of these compounds, the arsenic analogue of betaine hydrochloride and α-methyl-β-phenyleholine chloride have apparently not been prepared hitherto; the preparation of these and other compounds will be described in a later publication. It is desired to list the results obtained with the various substances but to reserve the larger part of the interpretation at present.

The writers believe that statements concerning the precise activity of various compounds in terms of choline chloride are unwise unless a large number of experiments have ken done in that dosage range where the relation between size of dose and lipotropic effect is most significant. Preliminary observations indicate, however, that N-betaine aldehyde chloride, N-Maine hydrochloride, and the P and As analogues of choline chloride are more than one-half as active as choline chloride.

It will be noted that the P and As betaines are not liptropic in action. This indicates that the P and As analogues of choline chloride act per se (or as the corresponding aldehydes) and suggests, therefore, that N-betaine hydrochloride acts by virtue of its conversion by the organism into choline chloride (or the corresponding aldehyde) and not per se.

The testing of the As analogue of betaine aldehyde chloride would appear to be the next step in the investigation of the mechanism of action of choline chloride. The synthesis of this compuond will be attemped in the near future. Other lines of investigation now in progress have suggested, however, that the oxidation of choline chloride to betaine aldehyde and betaine 1 which occurs in the liver and kidney of certain species (rats; 2 mouse and dog, recent observations of the writers) is probably not directly concerned with the mechanism by which choline chloride and its related compounds influence the deposition of fat in the liver.