The Hydrolysis of Fatty Acid Ethyl Esters in Low-Density Lipoproteins by Red Blood Cells, White Blood Cells and Platelets

Abstract

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been implicated as toxic mediators of ethanol ingestion. In this study, we investigated the in vitro hydrolysis of FAEE reconstituted in low-density lipoproteins (LDL) when incubated with human blood, cell free plasma, red blood cells, white blood cells, and platelets. We also determined the metabolic fate of the fatty acid originally incorporated in the FAEE following FAEE hydrolysis. When FAEE were incubated with human red blood cells, white blood cells, or platelets, at physiologic cell counts, 80% of the FAEE were hydrolyzed at 2 h. The FAEE-derived fatty acid was predominantly found in phospholipid and free fatty acid fractions. Cell free plasma contained minimal FAEE hydrolytic activity. These studies demonstrate that FAEE are degraded to free fatty acids and ethanol by the cellular elements in the blood. The generation of free fatty acids from extensive hydrolysis of FAEE adds support to the growing concept that at least some of the toxic effects of FAEE are mediated by the free fatty acids generated upon hydrolysis of the ethyl esters.