REDUCED FATTY-ACID ETHYL-ESTER SYNTHASE ACTIVITY IN THE WHITE BLOOD-CELLS OF ALCOHOLICS

Purpose: Fatty acid ethyl esters (FAEEs), esterification products of e thanol and fatty acids, have been implicated as mediators of ethanol-i nduced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the o rgans commonly damaged by ethanol abuse. Recently, we have made the ob servation that FAEEs are also present in the serum after ethanol inges tion. The current study was performed to determine whether cellular el ements of the blood and/or plasma are capable of synthesizing FAEEs fr om fatty acids and ethanol. Materials and Methods: Heparinized blood s amples were collected from 10 healthy volunteers, and the red blood ce lls, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subject s and individuals admitted to an alcoholic detoxification unit at a lo cal hospital were also assayed for FAEE synthase activity. Results: We observed that the FAEE synthase activity is present in whole blood, p rimarily within white blood cells. Fractionation of the white blood ce lls revealed that the lymphocyte-monocyte fraction isolated using Fico ll-hypaque contained similar to 3.5-fold higher activity than the gran ulocyte fraction. The cell type that contained the highest FAEE syntha se activity (1220 pmol/hr/10(6) cells) was the natural killer (NK) cel l population. B cells contained similar to 40% of the enzyme activity found in NK cells, and the B-cell activity was slightly greater than t hat found in CD4(+) and CD8(+) T cells. Having shown that FAEE synthas e exists in a blood cell, we subsequently demonstrated that alcoholic individuals have approximately half the white blood cell FAEE synthase activity of that found in normal controls. We also demonstrated that white blood cell FAEE synthase could be induced nearly 2-fold upon ing estion of 2 oz of scotch whiskey for 6 days. The enzyme activity retur ned to baseline levels despite ingestion of 2 oz of scotch whiskey/day for 3 additional days. Conclusions: These data indicate that ethanol ingestion results in increased FAEE production, particularly by NK cel ls. FAEE synthesis after ethanol ingestion may explain the presence of FAEE in the serum. The lower enzyme activity observed in white blood cells of alcoholics from a detoxification center may be the result of years of ethanol abuse or it may be that alcoholics congenitally have low levels of FAEE synthase. If the latter is true, this finding may e xplain in part the genetic predisposition of many alcoholic individual s to ethanol abuse.