Synthesis and degradation of fatty acid ethyl esters by cultured hepatoma cells exposed to ethanol

• Published in: The Journal of biological chemistry Vol. 265; no. 17; pp. 9688 - 9693
• Main Authors: LAPOSATA, E. A, HARRISON, E. H, HEDBERG, E. B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.06.1990
• Subjects: Animal cells; Animals; Biological and medical sciences; Cell cultures. Hybridization. Fusion; Cell Line; Esters; ethanol; Ethanol - metabolism; Fundamental and applied biological sciences. Psychology; hepatoma; Kinetics; Lipid Metabolism; Lipids - biosynthesis; Liver - metabolism; Liver Neoplasms, Experimental - metabolism; Molecular and cellular biology; Oleic Acid; Oleic Acids - metabolism; Phospholipids - biosynthesis; Rats; Triglycerides - biosynthesis; Cell culture; Ethanol; Rat; Enzyme; Liver; Rodentia; Lysosome; Biosynthesis; Alcohol dehydrogenase; Microsome; Metabolism; Fatty acids; Cholesterol; Esterification; Vertebrata; Mitochondria; Mammalia; Liver cell carcinoma
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)38725-3

Fatty acid ethyl esters are a family of neutral lipids that are the products of esterification of fatty acids with ethanol. Unlike other pathways of ethanol metabolism, ethyl esters are present in numerous human organs which are the targets of ethanol-induced damage. In the present study, we have shown that fatty acid ethyl esters are synthesized by a hepatoma cell line in tissue culture when exposed to ethanol concentrations easily attained by man during social drinking. Unlike alcohol dehydrogenase, the enzyme(s) responsible for synthesis of ethyl esters are membrane-bound and concentrated in the microsomal fraction of rat hepatocytes. In addition, fatty acid ethyl esters are hydrolyzed to free fatty acids and ethanol by membrane-bound enzyme(s) that are enriched in the microsomal and mitochondrial-lysosomal fractions. Intracellular hydrolysis of fatty acid ethyl esters release free fatty acids which are preferentially incorporated into cellular cholesterol esters. Thus, we have shown that a hepatocellular line exposed to concentrations of ethanol easily achieved in man by social drinking utilize endogenous fatty acids to form long-lived ethanol metabolites, fatty acid ethyl esters. Importantly, this family of neutral lipids may act as biochemical mediators of ethanol-induced cell damage, including the changes in cholesterol metabolism noted in chronic alcoholics.