Bilirubin Degradation system in Yeast Microsomes: Role of Cytochrome 2A6

Arthur, D., Wong, W., Ng, J. C., Moore, M. R. and Abu Bakar, A. (2007). Bilirubin Degradation system in Yeast Microsomes: Role of Cytochrome 2A6. In: C G Sobey and S Smid, 41st Annual Scientific Meeting of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists. SEAWP-RMP Joint meeting 10th Southeast Asian Western Pacific Regional Meeting of Pharmacologists with HBPRCA, Adelaide Hilton, Adelaide, S A, (). December 2 - 6, 2007.

Author Arthur, D.
Wong, W.
Ng, J. C.
Moore, M. R.
Abu Bakar, A.
Title of paper Bilirubin Degradation system in Yeast Microsomes: Role of Cytochrome 2A6
Conference name SEAWP-RMP Joint meeting 10th Southeast Asian Western Pacific Regional Meeting of Pharmacologists with HBPRCA
Conference location Adelaide Hilton, Adelaide, S A
Conference dates December 2 - 6, 2007
Proceedings title 41st Annual Scientific Meeting of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists
Place of Publication Victoria, Australia
Publisher ASCEPT
Publication Year 2007
Year available 2007
Sub-type Poster
ISSN 1322-4530
Editor C G Sobey
S Smid
Volume 12
Language eng
Abstract/Summary Oxidative metabolism of bilirubin (BR), a breakdown product of haem with cytoprotective and toxic properties, is an important route of detoxification in addition to glucuronidation. Bilirubin oxidases in this alternative disposal mechanism have been suggested and were shown to exist in the hepatic microsomal fractions of rats and mice. Previously, we have demonstrated that the mouse hepatic cytochrome P450 2a5 (Cyp2a5) is predominantly responsible for microsomal oxidation of bilirubin (Abu-Bakar et. al., 2005). In the present study we explore the potential of CYP2A6 (the human orthologue of the mouse Cyp2a5) to catalyse the oxidation of bilirubin in vitro. To achieve the aim we used microsomal fractions from the wild type-yeast and recombinant yeast expressing the human CYP2A6. Western blot analysis and coumarin hydroxylase activity assay showed that CYP2A6 is present in the microsomal fractions of the recombinant yeast but not the wild-type yeast. We also observed moderate difference in bilirubin oxidation rates between the wild type and recombinant yeast microsomes. The rates of bilirubin oxidation for wild type yeast were slower at 59 pmol bilirubin/min/nmol cytochrome P450 compared to that of the recombinant yeast expressing the human CYP2A6 protein at 84.6 pmol bilirubin/min/nmol cytochrome P450. The result suggests that cytochrome P450 isozyme(s) other than the CYP2A6 may contribute to the bilirubin oxidation in vitro. Currently, identification of the oxidative products formed from this reaction is being explored.
Subjects 270100 Biochemistry and Cell Biology
730299 Public health not elsewhere classified
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Q-Index Code EX

 
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Created: Wed, 14 May 2008, 15:20:45 EST by Marie-Louise Moore on behalf of National Res Centre For Environmental Toxicology