title: Hepatic cytochrome P450 enzymes belonging to the CYP2C subfamily from an Australian marsupial, the koala (Phascolarctos cinereus).
abstract: Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a diverse array of xenobiotics and endogenous substrates. We have previously reported that the obligate Eucalyptus feeder koala (Phascolarctos cinereus) exhibits a higher hepatic CYP2C activity as compared to non-Eucalyptus feeders human or rat, with stimulation of CYP2C activity by cineole. In the present study, we examine CYP2C expression by immunohistochemistry and describe the identification and cloning of koala CYP2Cs. Utilising anti-rat CYP2C6 antibody, the expression of CYP2C was found to be uniform across the hepatic sections, being consistent with that observed in human and rat. Two 1647 and 1638 bp koala liver CYP2C complete cDNAs, designated CYP2C47 and CYP2C48 respectively, were cloned by cDNA library screening. The koala CYP2C cDNAs encode a protein of 495 amino acids. Three additional partial CYP2C sequences were also identified from the koala, indicating the multiplicity of the CYP2C subfamily in this unique marsupial species. The results of this study demonstrate the presence of koala hepatic CYP2Cs that share several common features with other published CYP2Cs; however CYP2C47 and CYP2C48 contain four extra amino acid residues at the NH2-terminal, a transmembrane anchor which was reported being a fundamentally conserved structure core of all eukaryote CYP enzymes.
authors.affiliation: Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Jones
authors.forename: Adaweyah
authors.initials: A
authors.lastname: El-Merhibi
authors.forename: Suong N T
authors.initials: SN
authors.lastname: Ngo
authors.forename: Ieva
authors.initials: I
authors.lastname: Stupans
authors.forename: Ross A
authors.initials: RA
authors.lastname: McKinnon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification*; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D048368:Phascolarctidae; D051381:Rats; D017208:Rats, Wistar
chemical_list: C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System