title: Influence of lipid imbalance on butyrylcholinesterase activity and biotransformation efficiency.
abstract: Butyrylcholinesterase (EC 3.1.1.8, BChE) is highly active in plasma, skin and lung, the tissues that first contact xenobiotics, supporting a role for BChE in detoxication of xenobiotics including medicaments. A possible involvement of BChE in lipid metabolism has been suggested. Elevated BChE activity in obese individuals correlates with some parameters of lipid metabolism including increased levels of triacylglycerols (TAG) and cholesterol. The aim of this study was to estimate the BChE activity in rats on subcellular and inter-organ levels under the conditions of untreated and treated primary hypertriacylglycerolemia with the TAG lowering agent fenofibrate. No changes in BChE activity were observed in obese animals. However fenofibrate administration led to significant increase of BChE activity in all examined tissues (plasma, liver, white adipose tissue). The impact of lipid metabolic imbalance on BChE biotransformation ability was tested by measuring the rate of hydrolysis of 0,1 to 8 mM concentrations of the antimicrobial agent N-(2-benzoyloxyethyl)-ethyldimethylammonium bromide (BCH2). The results revealed a complete shift in the BChE kinetics in all studied models. In animals with hypertriacylglycerolemia the Km value of liver BChE rised 4,6-fold, but the total enzyme efficiency expressed as Vmax/Km dropped 40% comparing to control. In contrast, in animals treated with fenofibrate the BChE efficiency increased in liver 1,6-fold. We conclude here that BChE detoxification capacity is essentially altered under conditions of disturbed lipid metabolism. Clinically, this knowledge could be important in a view of xenobiotic elimination, especially when routinely prescribed medicaments are concerned.
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic. katarina.siskova@gmail.com
authors.forename: K
authors.initials: K
authors.lastname: Sisková
authors.forename: F
authors.initials: F
authors.lastname: Bilka
authors.forename: A
authors.initials: A
authors.lastname: Adameová
authors.forename: A
authors.initials: A
authors.lastname: Balazová
authors.forename: M
authors.initials: M
authors.lastname: Mydla
authors.forename: I
authors.initials: I
authors.lastname: Pauliková
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001588:Benzoylcholine / Q000378:metabolism; D001711:Biotransformation; D001835:Body Weight / Q000502:physiology; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004032:Diet; D011345:Fenofibrate / Q000494:pharmacology; D006949:Hyperlipidemias / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000960:Hypolipidemic Agents; D014280:Triglycerides; D001588:Benzoylcholine; D012313:RNA; D002091:Butyrylcholinesterase; D011345:Fenofibrate