Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics

Norbert P. Gorski, Hazem Nouraldin, David M. Dube, Frederic I. Preffer, David M. Dombkowski, Ellen M. Villa, Kent B. Lewandrowski, Roger D. Weiss, Cathryn Hufford, Michael Laposata

Research output: Contribution to journalArticle

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Abstract

Purpose: Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol- induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol. Materials and Methods: Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity. Results: We observed that the FAEE synthase activity is present in whole blond, primarily within white blond cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained ~3.5-fold higher activity than granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/106 cells) was the natural killer (NK) cell population. B cells contained ~40% of the enzyme activity found in NK cells, and the B- cell activity was slightly greater than that found in CD4+ and CD8+ T cells. Having shown that FAEE synthase 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 ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned 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 cells. 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. It the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse.

Original languageEnglish (US)
Pages (from-to)268-274
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume20
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Alcoholics
Leukocytes
Blood
Ethanol
Fatty Acids
Cells
Esters
Eating
Enzyme activity
Natural Killer Cells
Detoxification
Enzymes
B-Lymphocytes
Diatrizoate
fatty acyl ethyl ester synthase
Ficoll
Plasmas
Esterification
T-cells
Lymphocytes

Keywords

  • Alcohol
  • Alcoholism
  • Ethanol
  • Fatty Acids
  • Natural Killer Cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics. / Gorski, Norbert P.; Nouraldin, Hazem; Dube, David M.; Preffer, Frederic I.; Dombkowski, David M.; Villa, Ellen M.; Lewandrowski, Kent B.; Weiss, Roger D.; Hufford, Cathryn; Laposata, Michael.

In: Alcoholism: Clinical and Experimental Research, Vol. 20, No. 2, 1996, p. 268-274.

Research output: Contribution to journalArticle

Gorski, NP, Nouraldin, H, Dube, DM, Preffer, FI, Dombkowski, DM, Villa, EM, Lewandrowski, KB, Weiss, RD, Hufford, C & Laposata, M 1996, 'Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics', Alcoholism: Clinical and Experimental Research, vol. 20, no. 2, pp. 268-274. https://doi.org/10.1111/j.1530-0277.1996.tb01639.x
Gorski, Norbert P. ; Nouraldin, Hazem ; Dube, David M. ; Preffer, Frederic I. ; Dombkowski, David M. ; Villa, Ellen M. ; Lewandrowski, Kent B. ; Weiss, Roger D. ; Hufford, Cathryn ; Laposata, Michael. / Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics. In: Alcoholism: Clinical and Experimental Research. 1996 ; Vol. 20, No. 2. pp. 268-274.
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abstract = "Purpose: Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol- induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol. Materials and Methods: Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity. Results: We observed that the FAEE synthase activity is present in whole blond, primarily within white blond cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained ~3.5-fold higher activity than granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/106 cells) was the natural killer (NK) cell population. B cells contained ~40{\%} of the enzyme activity found in NK cells, and the B- cell activity was slightly greater than that found in CD4+ and CD8+ T cells. Having shown that FAEE synthase 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 ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned 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 cells. 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. It the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse.",
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T1 - Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics

AU - Gorski, Norbert P.

AU - Nouraldin, Hazem

AU - Dube, David M.

AU - Preffer, Frederic I.

AU - Dombkowski, David M.

AU - Villa, Ellen M.

AU - Lewandrowski, Kent B.

AU - Weiss, Roger D.

AU - Hufford, Cathryn

AU - Laposata, Michael

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N2 - Purpose: Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol- induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol. Materials and Methods: Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity. Results: We observed that the FAEE synthase activity is present in whole blond, primarily within white blond cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained ~3.5-fold higher activity than granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/106 cells) was the natural killer (NK) cell population. B cells contained ~40% of the enzyme activity found in NK cells, and the B- cell activity was slightly greater than that found in CD4+ and CD8+ T cells. Having shown that FAEE synthase 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 ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned 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 cells. 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. It the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse.

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