FATTY-ACID ETHYL-ESTERS AND HEPG2 CELLS - INTRACELLULAR SYNTHESIS ANDRELEASE FROM THE CELLS

Fatty acid ethyl eaters (FAEE), esterification prodlucts of fatty acid and ethanol, have been implicated as mediators of ethanol-induced org an damage. To understand the molecular and cellular events in FAEE syn thesis and secretion, we developed a system in which HepG2 cells synth esize and release FAEE into the culture medium upon incubation with et hanol. The synthesis of FAEE was observed within 5 min of the addition of ethanol, with a plateau for FAEE synthesis after 2 h of incubation , It was also observed that FAEE are synthesized by both a microsomal FAEE synthase, which preferentially uses fatty acyl-CoA as a substrate , and a cytosolic FAEE synthase, which accepts both unesterified fatty acid and fatty acyl-CoA as substrates with a slight preference for fa tty acyl-CoA. Although the kinetics of cellular FAEE synthesis await f urther characterization, the intracellular fatty acid substrate appear s to be derived principally from glycerolipids and other esters, FAEE were released into the culture medium by a mechanism independent of th e vesicular transport pathway. Lipoprotein particles and albumin were found to be carriers of FAEE after FAEE secretion from the cell.