Possible role of long chain fatty acid ethyl esters in organ injury and as short-term markers of ethanol intake in humans

Abstract

Ingested ethanol is mainly oxidized to acetaldehyde and acetate in the liver and oxidative metabolites of ethanol have been implicated in organ injury. More recently, fatty acid ethyl esters (FAEEs), non-oxidative metabolites of ethanol, have been shown to be present in blood and in a number of organs with low or no capacity to oxidize ethanol, after alcohol intake. As such esters may have detrimental effects on subcellular structures, they have been proposed as possible mediators of injury in organs lacking oxidative ethanol metabolism. Two enzyme activities, acyl-CoA; ethanol O-acyltransferase (AEAT) and fatty acid ethyl ester (FAEE) synthase have the ability to esterify fatty acids to ethanol. We have characterized these two activities in rat and human liver microsomes and measured the activities in various human organs. Our data strongly suggest that AEAT is of major importance for the formation of FAEEs both in rat and in humans. Of the human tissues tested, liver had the clearly highest FAEE-synthesizing activity, but high activity was also found in intestinal mucosa. Pancreas contained relatively low capacity to synthesize FAEEs (with AEAT and FAEE synthase activities being comparable). Liver and pancreas contained very high FAEE hydrolyzing activity, while it was very low in intestine. Considering the central role of the intestine in uptake and esterification of fatty acids, and uptake of ingested alcohol, intestine is likely to be an important site for the synthsis of FAEEs. In addition, human serum contains very low FAEE hydrolyzing activity which can account for the observed elevation of FAEEs in blood during alcohol intake. In a controlled alcohol intake experiment we found that FAEEs appeared rapidly in the blood, with increased levels being detectable several hours after disappearence of blood ethanol. These data suggest that FAEEs may be used as a short term marker for ethanol intake.KeywordsLiver MicrosomeOrgan InjuryHuman Liver MicrosomeEthanol IntakeMicrosomal ProteinThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.