Abstract
Ingested ethanol is mainly oxidized to acetaldehyde and acetate in the liver and oxidative metabolites of ethanol have been implicated in organ injury. More recently, fatty acid ethyl esters (FAEEs), non-oxidative metabolites of ethanol, have been shown to be present in blood and in a number of organs with low or no capacity to oxidize ethanol, after alcohol intake. As such esters may have detrimental effects on subcellular structures, they have been proposed as possible mediators of injury in organs lacking oxidative ethanol metabolism. Two enzyme activities, acyl-CoA; ethanol O-acyltransferase (AEAT) and fatty acid ethyl ester (FAEE) synthase have the ability to esterify fatty acids to ethanol. We have characterized these two activities in rat and human liver microsomes and measured the activities in various human organs. Our data strongly suggest that AEAT is of major importance for the formation of FAEEs both in rat and in humans. Of the human tissues tested, liver had the clearly highest FAEE-synthesizing activity, but high activity was also found in intestinal mucosa. Pancreas contained relatively low capacity to synthesize FAEEs (with AEAT and FAEE synthase activities being comparable). Liver and pancreas contained very high FAEE hydrolyzing activity, while it was very low in intestine. Considering the central role of the intestine in uptake and esterification of fatty acids, and uptake of ingested alcohol, intestine is likely to be an important site for the synthsis of FAEEs. In addition, human serum contains very low FAEE hydrolyzing activity which can account for the observed elevation of FAEEs in blood during alcohol intake. In a controlled alcohol intake experiment we found that FAEEs appeared rapidly in the blood, with increased levels being detectable several hours after disappearence of blood ethanol. These data suggest that FAEEs may be used as a short term marker for ethanol intake.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Abbreviations
- AEAT:
-
acyl-coenzyme A:ethanol O-acyltransferase
- FAEE:
-
fatty acid ethyl ester
- ES-4 and ES-10:
-
rat liver microsomal carboxylesterases
- BNPP:
-
bis-(4-nitrophenyl) phosphate
- p-HMB:
-
p-hydroxymercu-ribenzoic acid.
References
Alexson S. E. H., Mentlein R., Wernstedt C. and Hellman U. 1993 Isolation and characterization of microsomal acyl-CoA thioesterase: A member of the rat liver microsomal carboxylesterase multi-gene family. Eur. J. Biochem. 214, 719–727.
Berge R. K. 1979 Purification and characterization of a long-chain acyl-CoA hydrolase from rat liver microsomes. Biochim. Biophys. Acta 574, 321–333.
Björkhem I. 1976 On the mechanism of regulation of ω-oxidation of fatty acids. J. Biol. Chem. 251, 5259–5266.
Bora P. S., Guruge D. G., Miller D. D., Chaitman B. R. and Ruyle M. S. 1996 Purification and characterization of human heart fatty acid ethyl ester synthase/carboxylesterase. J. Mol. Cell Cardiol. 28, 2027–2032.
Bora P. S., Spilburg C. A. and Lange L. G. 1989 Metabolism of ethanol and carcinogens by glutathione transferases. Prot. Natl. Acad. Sci. USA 86, 4470–4473.
Bradford M. M. 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein/dye binding. Anal. Biochem. 72, 248–254.
Chang W., Waltenbaugh C. and Borensztajn J. 1997 Fatty acid ethyl ester synthesis by isolated perfused rat heart. Metabolism 46, 926–929.
Dan L. and Laposata M. 1997 Ethyl palmitate and ethyl oleate are the predominant fatty acid ethyl esters in the blood after ethanol ingestion and their synthesis is differentially influenced by the extracellular concentrations of their corresponding fatty acids. Alcohol. Clin. Exp. Res. 21; 2, 286–292.
Diczfalusy M. A., Björkhem I., Einarsson C. and Alexson S. E. H. 1999 Formation of fatty acid ethyl esters in rat liver microsomes. Evidence for a key role of acyl-CoA: ethanol O-acyltransferase. Eur. J. Biochem. 259, 404–411.
Doyle K. M., Bird D. A., Al-Salihi S., Hallaq J., Cluette-Brown J. E., Goss K. A. and Laposata M. 1994 Fatty acid ethyl esters are present in human serum after ethanol ingestion. J. Lipid Res. 35, 428–437.
Doyle K. M., Cluette-Brown J. E., Dube D. M., Bernhard T. G., Morse C. R. and Laposata M. 1996 Fatty acid ethyl esters in the blood as markers for ethanol intake. J.AM.A. 276, 1152–1156.
Einarsson K., Benthin L., Ewerth S., Hellers G., Stahlberg D. and Angelin B. 1989 Studies on acylcoenzyme Axholesterol acyltransferase activity in human liver microsomes. J. Lipid Res. 30, 739–746.
Haber P. S., Wilson J. S., Apte M. V. and Pirola R. C. 1993 Fatty acid ethyl esters increase rat pancreatic lysosomal fragility. J. Lab. Clin. Med. 121, 759–764.
Kabakibi A., Morse C. R. and Laposata M. 1998 Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells. J. Lipid Res. 39, 1568–1582.
Kaphalia B. S., Fritz R. R. and Ansari G. A. S. 1997 Purification and characterization of rat liver microsomal fatty acid ethyl and 2-chloroethyl ester synthase and their relationship with carboxylesterase (pI 6.1). Chem. Res. Toxicol. 10, 211–218.
Lange L. G. and Sobel B. 1983 Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol. J. Clin. Invest. 72, 724–731.
Laposata E. A. and Lange L. G. 1986 Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 231, 497–499.
Lieber C. S. 1985 Alcohol and the liver: metabolism of ethanol, metabolic effects and pathogenesis of injury. ActaMed. Scand. Suppl. 703, 11–55.
Mentlein R., Suttorp M. and Heymann E. 1984 Specificity of purified monoacylglycerol lipase, palmitoyl-CoA hydrolase, palmitoyl-carnitine hydrolase, and nonspecific carboxylesterase from rat liver microsomes. Arch. Biochem. Biophys. 228, 230–246.
Polokoff M. A. and Bell R. M. 1978 Limited palmitoyl-CoA penetration into microsomal vesicles as evidenced by a high latent ethanol acyltransferase activity. J. Biol. Chem. 253, 7173–7178.
Riley D. J. S., Kyger E. M., Spilburg C. A. and Lange L. G. 1990 Pancreatic cholesterol esterases. 2. Purification and characterization of human pancreatic fatty acid ethyl ester synthase. Biochemistry 29, 3848–3852.
Soderberg B. L., Sicinska E. T., Blodget E., Cluette-Brown J. E., Suter P. M., Schuppisser T., Vetter W. and Laposata M. 1999 Preanalytical variables affecting the quantification of fatty acid ethyl esters in plasma and serum samples. Clin. Chem. 45, 2183–2190.
Szczypiorkowski Z. M., Dickersin G. R. and Laposata M. 1995 Fatty acid ethyl esters decrease human hopatoblastoma cell proliferation and protein synthesis. Gastroenterology 108, 515–522.
Tsujita T. and Okuda H. 1992 Fatty acid ethyl ester synthase in rat adipose tissue and its relationship to carboxylesterase. J. Biol. Chem. 267, 23489–23494.
Tsujita T. and Okuda H. 1994 The synthesis of fatty acid ethyl ester by carboxylester lipase. Eur. J. Biochem. 224, 57–62.
Wada F., Usami M, Goto M. and Hayashi T. 1971 Studies on the physiological significance of fatty acid ω-oxidation. J. Biochem. 70, 1065–1067.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Steinkopff Verlag Darmstadt
About this paper
Cite this paper
Diczfalusy, M.A., von Wachenfeldt, M., Holmberg, I., Alexson, S.E.H. (2001). Possible role of long chain fatty acid ethyl esters in organ injury and as short-term markers of ethanol intake in humans. In: Wurst, F.M. (eds) New and Upcoming Markers of Alcohol Consumption. Steinkopff. https://doi.org/10.1007/978-3-642-96008-6_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-96008-6_2
Publisher Name: Steinkopff
Print ISBN: 978-3-642-96010-9
Online ISBN: 978-3-642-96008-6
eBook Packages: Springer Book Archive