Metabolism of ethanol by human brain to fatty acid ethyl esters

Although the most prominent acute and chronic effect of alcohol ingestion in man is alteration of brain function, metabolism of ethanol by human brain has not been documented. This study was designed to detect and localize a new family of nonoxidative ethanol metabolites, fatty acid ethyl esters, in human brain and characterize their synthetic pathways. Fatty acid ethyl ester synthase activity was present in 10 different locations in human brain, with gray matter containing more activity than white matter (0.53 nmol of ethyl oleate/mg of protein/h and 0.25 nmol of ethyl oleate/mg of protein/h, respectively). Two forms of this synthase, present in cytosol or loosely bound to membrane fractions, were isolated from human gray and white matter and then partially purified by ion-exchange chromatography. Both were active at low ethanol concentrations easily attained in vivo in man. Importantly, fatty acid ethyl esters were also detected in brains of individuals dying while intoxicated; only small amounts were present in control subjects at autopsy. Thus, alcohol metabolism in human brain has been documented for the first time by identifying both fatty acid ethyl esters and their synthases in this important target-organ of alcohol abuse.