TY - JOUR
T1 - Flavin-containing monooxygenase activity in camel tissues
T2 - Comparison with rat and human liver enzymes
AU - Raza, Haider
AU - Bhagwat, Shripad V.
AU - John, Annie
N1 - Funding Information:
The authors wish to acknowledge the support from the FMHS Research Committee Fund and the UAE Terry Fox Cancer Research Fund (to HR). Authors also wish to acknowledge the support from the laboratory of Dr N.G. Avadhani (NIH Grant GM 49683) University of Pennsylvania, Philadelphia, USA.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Camel tissues
KW - Cytochrome P450
KW - Human and rat livers
KW - Methimazole
KW - Microsomal flavin-containing monooxygenase
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U2 - 10.1016/j.cca.2004.12.004
DO - 10.1016/j.cca.2004.12.004
M3 - Article
C2 - 15683840
AN - SCOPUS:15944375892
SN - 1532-0456
VL - 139
SP - 289
EP - 293
JO - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
JF - Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
IS - 4
ER -