Characterization of enzymes involved in formation of ethyl esters of long-chain fatty acids in humans

Elevated fatty acid ethyl ester (FAEE) concentrations have been detected in postmortem organs from alcoholics and patients acutely intoxicated by alco hol, and FAEE have been implicated as mediators of ethanol-induced organ da mage, The formation of FAEE is catalyzed by acyl-coenzyme A:ethanol O-acylt ransferase (AEAT) and by FAEE synthase, which utilize acyl-CoA and free fat ty acids, respectively, as substrates, Because little is known about the ca pacity of various human tissues to synthesize and hydrolyze FAEE, we invest igated formation of FAEE by AEAT and FAEE synthase in tissue homogenates fr om human gastric ventricular and duodenal mucosa, pancreas, liver, heart, l ung, and adipose tissue, gallbladder mucosa, and in serum. Liver, duodenal mucosa, and pancreas were found to have the highest capacities to synthesiz e FAEE, mainly due to AEAT. FAEE hydrolyzing activity was highest in liver and pancreas, but hardly detectable in adipose tissue or heart.jlr Because fatty acids and alcohol are absorbed by the intestinal mucosa, intestine ma y be a major site of FAEE synthesis, and FAEE may be delivered via the circ ulation to other organs and taken up by lipoprotein receptor-mediated uptak e. h very low rate of FAEE hydrolysis was detected in heart and adipose tis sue, which probably accounts for the previously observed accumulation of FA EE in these organs.