Nonoxidative alcohol metabolism catalyzed by fatty acid ethyl ester (FAEE) synthases may contribute to extrahepatic injury resulting from alcohol abuse. Unlike rabbit myocardial FAEE synthase, that from human heart has a satellite minor synthase (I) eluting from DEAE cellulose at a conductivity of 5 mS. Synthase I was purified 1,118-fold to homogeneity by sequential gel permeation, hydrophobic interaction, and Superose-12 fast-protein liquid chromatographies. SDS-PAGE showed a single polypeptide with a molecular mass of 26 kD and gel permeation chromatography indicated a molecular mass of 52 kD for the active enzyme. Homogeneous synthase I catalyzed ethyl ester synthesis at highest rates with unsaturated octadecanoic fatty acid substrates. The amino acid composition of synthase I was highly homologous to that of human myocardial major synthase, recently identified as an acidic glutathione (GSH) S-transferase. Antibody raised against homogeneous human heart major synthase cross-reacted with the 26-kD synthase I. FAEE synthase co-chromatographed with GSH S-transferase on DEAE cellulose, Sephadex G-100 and S-hexylglutathione agarose, and also displayed GSH S-transferase activity in catalyzing the conjugation of GSH with nitrobenzene-containing carcinogens. Thus, human myocardium contains a satellite peak of FAEE synthase activity and it is a neutral GSH S-transferase.
P S Bora, C A Spilburg, L G Lange
Title and authors | Publication | Year |
---|---|---|
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Biochemical and Biophysical Research Communications | 2003 |
Effects of L-carnitine on the formation of fatty acid ethyl esters in brain and peripheral organs after short-term ethanol administration in rat
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Neurochemical Research | 1999 |
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Progress in Lipid Research | 1998 |
Fatty acid ethyl esters: nonoxidative metabolites of ethanol
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Addiction Biology | 1998 |
Cardiac Metabolism in Health and Disease
S Abdel-Aleem, JE Lowe |
1998 | |
Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells
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Journal of lipid research | 1998 |
Mutagenesis and characterization of specific residues in fatty acid ethyl ester synthase: a gene for alcohol-induced cardiomyopathy
P S Bora, D D Miller, B R Chaitman |
Molecular and Cellular Biochemistry | 1998 |
Fatty acid ethyl ester synthesis by the isolated perfused rat heart
W Chang, C Waltenbaugh, J Borensztajn |
Metabolism | 1997 |
Human fatty acid ethyl ester synthase-III gene: genomic organization, nucleotide sequencing and chromosomal localization
P S Bora, B L Guruge, D D Miller, B R Chaitman, W Fortson |
Molecular and Cellular Biochemistry | 1997 |
Myocardial Cell Damage by Fatty Acid Ethyl Esters
PS Bora, MA Farrar, DD Miller, BR Chaitman, BL Guruge |
Journal of Cardiovascular Pharmacology | 1996 |
Identification of fatty acid methyl ester as naturally occurring transcriptional regulators of the members of the peroxisome proliferator-activated receptor family
A Schmidt, RL Vogel, KM Witherup, SJ Rutledge, SM Pitzenberger, M Adam, GA Rodan |
Lipids | 1996 |
Fatty acid ethyl ester synthesis by human liver microsomes
T Treloar |
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | 1996 |
Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis
ZM Szczepiorkowski, GR Dickersin, M Laposata |
Gastroenterology | 1995 |
Comparison of the induction of rat glutathione S-transferase and fatty acid ethyl ester synthase activities
GP Carlson, AM Chaney, F Jiang |
Toxicology | 1995 |
Fatty acid conjugates of xenobiotics
GA Ansari, BS Kaphalia, MF Khan |
Toxicology Letters | 1995 |
Advances in Pharmacology
B Drenger, Y Ginosar, Y Gozal |
Advances in Pharmacology | 1994 |
Molecular Mechanism of Ethanol Metabolism by Human Brain to Fatty Acid Ethyl Esters
PS Bora, LG Lange |
Alcoholism, clinical and experimental research | 1993 |
Evidence against a relationship between fatty acid ethyl ester synthase and the Pi class glutathione S-transferase in humans
P Board, S Smith, J Green, M Coggan, T Suzuki |
The Journal of biological chemistry | 1993 |
Nonoxidative ethanol metabolism: Expression of fatty acid ethyl ester synthase-III in cultured neural cells
KE Isenberg, PS Bora, X Zhou, X Wu, BW Moore, LG Lange |
Biochemical and Biophysical Research Communications | 1992 |
Site-specific mutagenesis of two histidine residues in fatty acid ethyl ester synthase-III
PS Bora, X Wu, LG Lange |
Biochemical and Biophysical Research Communications | 1992 |
Purification and characterization of fatty acid ethyl ester synthase-II from human myocardium
PS Bora, X Wu, CA Spilburg, LG Lange |
The Journal of biological chemistry | 1992 |
Mechanism of Fatty Acid Ethyl Ester Formation and Biological Significance
LG Lange |
Annals of the New York Academy of Sciences | 1991 |
Homogeneous Synthase I from Human Myocardium is a Glutathione S-Transferase
PS Bora, LG Lange |
Annals of the New York Academy of Sciences | 1991 |
Independent segregation of glutathione S-transferase and fatty acid ethyl ester synthase from pancreas and other human tissues
R Sharma, S Gupta, SS Singhal, H Ahmad, A Haque, YC Awasthi |
Biochemical Journal | 1991 |
Purification and characterization of glutathione S-transferases from rat pancreas
SS Singhal, S Gupta, M Saxena, R Sharma, H Ahmad, GA Ansari, YC Awasthi |
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | 1991 |
Liver Pathology and Alcohol
RR Watson |
1991 | |
The Genetic Basis of Alcohol and Drug Actions
JC Crabbe, RA Harris |
1991 | |
Molecular cloning, sequencing, and expression of human myocardial fatty acid ethyl ester synthase-III cDNA
PS Bora, NS Bora, XL Wu, LG Lange |
The Journal of biological chemistry | 1991 |
Do the major human glutathione S-transferases have fatty acid ethyl ester synthase activity?
T Suzuki, MS Kovacs, PG Board |
FEBS Letters | 1990 |