Journal article
An in Vivo Pilot Study Characterizing the New CYP2A67, 8, and 10 Alleles
Biochemical and biophysical research communications, Vol.290(1), pp.318-324
01/11/2002
Handle:
https://hdl.handle.net/2376/117687
PMID: 11779172
Abstract
We developed genotyping assays for CYP2A6*7 (Ile471Thr) and CYP2A6*8 (Arg485Leu). We found higher allelic frequencies in Japanese and Chinese versus Caucasians and identified an allele in which both substitutions occur together (CYP2A6*10). We created a homology model for predicting the impact of allelic variants on enzymatic activity and subsequently tested this in vivo in a pilot kinetic study. Consistent with our homology model predictions, we found (i) that CYP2A6*7 produces an enzyme that has decreased (not inactive) activity for metabolizing nicotine and coumarin; (ii) that CYP2A6*8 is unlikely to affect catalytic activity in vivo; and (iii) that having both substitutions together on an allele (CYP2A6*10) dramatically reduces function and may be fully inactive for some substrates. In conclusion, this study identifies, at relatively high frequency in Asians, an allele with decreased activity (may be substrate selective), a fully functional allele, and an allele containing both substitutions in which function is dramatically reduced.
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Details
- Title
- An in Vivo Pilot Study Characterizing the New CYP2A67, 8, and 10 Alleles
- Creators
- C Xu - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8Y.S Rao - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8B Xu - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8E Hoffmann - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8J Jones - Department of Chemistry, Washington State University, Pullman, Washington, 99163E.M Sellers - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8R.F Tyndale - Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada, M5S 1A8
- Publication Details
- Biochemical and biophysical research communications, Vol.290(1), pp.318-324
- Academic Unit
- Chemistry, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900548015701842
- Language
- English
- Resource Type
- Journal article