Relationship of ethanol to choline metabolism in the liver: a review

Abstract

Despite the fact that ethanol ingestion and choline deficiency appear to have related effects on the liver, no one has demonstrated a true relationship of ethanol metabolism to choline metabolism in this organ. We, in this laboratory, have developed a technique for the quantitative measurement of choline uptake by the isolated perfused liver that has served as a convenient model for studies involving hepatic ethanol-choline relationships. These studies have shown that a specific choline oxidase antagonist, 2 amino-2-methyl-1-propanol, and two nonspecific choline oxidase inhibitors depressed hepatic choline uptake indicating that this uptake is primarily a function of the choline oxidative pathway. Circulation of ethanol in liver perfusates or chronically feeding ethanol to rats was found to enhance choline uptake. Inhibition of this ethanol-induced increase by pyrazole suggests that ethanol must be metabolized to produce its effect. Investigation of the effects of two metabolic products of ethanol, acetate and NADH, demonstrated that increased NADH generation due to hepatic ethanol metabolism may be responsible for the observed increase in choline utilization. The ability of the choline oxidase inhibitor to block the effect of ethanol suggests that the increased choline requirement due to alcohol may be the result of ethanol metabolism stimulating the oxidative degradation of choline in the liver.