Drug and xenobiotic metabolising enzymes in camel liver: multiple forms and species specific expression.
1. Previous studies have demonstrated the presence of phase I mixed-function oxidases (cytochrome P450-dependent) and phase II conjugation (glutathione S-transferase) enzymes in camel liver. This study represents further characterisation of these drug metabolising enzyme systems in camel liver by comparing their catalytic and immunochemical properties with enzymes of rat and mouse liver. 2. Using the specific P450 substrate aniline, the microsomal aniline hydroxylase activity of camel liver was found to be significantly lower than that of rat and mouse. The Km values of the enzyme for aniline was similar in rat and camel liver; however, the Vmax for camel liver enzyme was 50% of the rat liver enzyme. Aminopyrene N-demethylase activity in camel liver, was lower than that of rat but higher than in mouse. Microsomal NADPH cytochrome C-reductase and NADPH-supported lipid peroxidation activities were similar in all three species. 3. The cytosolic phase II conjugation enzyme glutathione S-transferase and glutathione peroxidase activities in camel liver were markedly lower than those of rat and mouse enzymes. However, GSH concentration was similar in all three species. 4. Immunodot blot and Western blot analysis of liver cytosols, using antibodies to specific GST isoenzymes, have shown that camel liver like mouse and rat, expresses predominantly the Alpha and Mu classes of GST. GST Pi on the other hand, was abundant in mouse liver and was underexpressed in camel and rat liver. 5. Our results demonstrate that there are multiple forms of phase I (P450) and phase II (GST) enzymes in camel liver and that they are comparable with the drug metabolising enzymes of rat and mouse.(ABSTRACT TRUNCATED AT 250 WORDS)
Raza
H
H
Department of Biochemistry, Faculty of Medicine and Health Sciences, U.A.E. University, Al Ain, United Arab Emirates.
Montague
W
W
D000818:Animals; D002162:Camelus / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats / Q000378:metabolism*; D013045:Species Specificity; D015262:Xenobiotics / Q000378:metabolism*
D007527:Isoenzymes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase