Flavin-containing monooxygenase activity in camel tissues: comparison with rat and human liver enzymes.
We previously reported the occurrence of multiple forms of drug metabolizing enzymes in camel tissues. In this study, we demonstrated for the first time, flavin-containing monooxygenase (FMO)-dependent metabolism of two model substrates methimazole (MEM) and N,N'-dimethylaniline (DMA) by camel liver, kidney, brain and intestine. FMO-catalyzed metabolism in the microsomes of camel tissues was independent of cytochrome P450 (CYP) activity and exhibited a pH and temperature dependence characteristic of FMO enzymes. Use of inhibitors of CYP activities, SKF525A, octylamine or antibody against NADPH-P450 reductase, did not significantly alter the FMO-dependent substrate metabolism. Using MEM as a model substrate for FMO activity, we show that camel liver has an activity similar to that in rat and human livers. MEM metabolism in extrahepatic tissues in camels was significantly lower (60%-80%) than that in liver. Our results suggest occurrence of FMO in camel tissues, with catalytic properties similar to those in rat and human livers. These results may help in better understanding the effects of pharmacologically and toxicologically active compounds administered to camels.
Raza
Haider
H
Department of Biochemistry, Faculty of Medicine and Health Sciences, P.O. Box 17666, UAE University, Al Ain, United Arab Emirates. h.raza@uaeu.ac.ae
Bhagwat
Shripad V
SV
John
Annie
A
D000328:Adult; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002162:Camelus / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000814:Aniline Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D009249:NADP; D008713:Methimazole; C015157:N,N-dimethylaniline; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases