Utilization of the Arsenic Analogue of Choline Chloride in the Bio-Synthesis of Phospholipid

Abstract

The mechanism by which choline chloride influences the deposition of fat in the liver is by no means clear. Best, Channon and others have shown that this nitrogenous component of lecithin is capable of preventing or curing the fatty infiltration of the liver which is produced in the rat on a high fat diet or in the dog on a lean meat-sucrose diet. The finding that diets essentially free of choline cause an infiltration of fat into the livers of rats, a condition curable by the addition of choline chloride to the diets, led Best, et al., to suggest that choline may be an essential dietary factor.

The most obvious hypothesis as regards the manner in which choline produces its “lipotropic” effect would involve perhaps the formation of lecithins and other choline-containing phospholipids from fat, phosphate and ingested choline, thus favoring the transport of lipid materials. There are obstacles to the immediate acceptance of such a view, of possible significance among which is the lipotropic inactivity of aminoethanol, the nitrogenous constituent of the phospholipid cephalin. Of greater import is the finding (Best, et al.) that betaine, the naturally occurring acid corresponding to choline, is lipotropically active. This substance is incapable of entering into the formation of phospholipids unless it is first reduced to choline by the organism, a conversion which would be of considerable biochemical interest.

Pharmacological investigations of the phosphorus and arsenic analogues of choline and acetylcholine, 1 , 2 molecules in which arsenic replaces nitrogen as the nuclear element, suggested that the arsenic analogue of choline chloride (“arsenocholine” chloride) might prove useful in furnishing essentially a “tagged molecule” the assimilation of which by the organism might be followed.