Nonoxidative ethanol metabolism in human leukocytes: detection of fatty acid ethyl ester synthase activity |
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Authors: | M Wright K J Bieser P M Kinnunen L G Lange |
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Affiliation: | 1. Department of Biotechnology, School of Biosciences, Periyar University, Salem 636011, India;2. Department of Botany, School of Life Sciences, Periyar University, Salem 636011, India;3. Department of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli 620024, India;1. Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, 211007, India;2. Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, 454008, Russia;3. Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, 10000, Croatia;4. Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unayzah, 56264, Saudi Arabia;5. Natural Product Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, 211007, India;6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, 110062, India;1. University of Science and Technology Beijing, Beijing 100083, China;2. Jiangsu University of Science and Technology, Zhenjiang 212100, China;1. Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Bühlstrasse 20, 3012 Bern, Switzerland;2. Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland;3. Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, c/o Theodor Kocher Institute, Freiestrasse 1, 3012 Bern, Switzerland;1. Surface Engineering Division, Council of Scientific and Industrial Research - National Aerospace Laboratories, Bangalore, India;2. Department of Physics and Nanotechnology, SRM Institute of Science and Technology, Tamil Nadu 603203, India;3. Department of Mechanical Engineering, School of Engineering & Applied Sciences, SRM University, AP – Amaravati, Andhra Pradesh 522502, India;1. Pharmacognosy Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Department of Biochemistry, Faculty of Agriculture, Minia University, Minia 61519, Egypt;3. Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt;4. Department of Biology, University of Iowa, Iowa City, IA 52242-1324, USA;5. Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia |
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Abstract: | Oxidative pathways of alcohol metabolism such as alcohol dehydrogenase usually are not present in human blood and therefore clinical studies correlating ethanol metabolism with alcohol abuse syndromes have not been performed. To assess the activity of nonoxidative ethanol metabolism in blood, we assayed for the activity of fatty acid ethyl ester synthase, a pathway recently described as abundant in the human organs most commonly damaged by alcohol. Indeed, peripheral human leukocytes contain detectable fatty acid ethyl ester synthase activity: 1.2 X 10(6) leukocytes from 10 ml blood catalyze the synthesis of ethyl oleate at 1.4 nmol/4 hr. The reaction is linear with respect to cell number and expended time; Km oleate = 600 microM, Km ethanol = 600 mM. DEAE cellulose chromatography partially purifies synthase activity into a minor and major form (activity ratio = 10/1). Thus, gene products exist in human blood that recognize ethanol and whose biological activity is conveniently assayable for clinical investigations of alcohol metabolism and abuse. |
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