کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2479399 | 1113444 | 2009 | 8 صفحه PDF | دانلود رایگان |

Summary:Human flavin-containing monooxygenase 3 (FMO3)-mediated microsomal oxygénation activity, levels of FMO3 protein and FMO3 mRNA and modifications were investigated in Japanese livers genotyped for the FMO3 gene. Significant correlations were observed for benzydamine N-oxygenation or methyl p-tolyl sulfide S-oxygenation activity (in the range of ~ 20-to ~ 40-fold) and FMO3 levels determined immunochemically in liver microsomes (r2 = 0.73-0.75, p< 0.0001, n = 16). Preincubation with the reducing agent ascorbate revealed that FMO3 activity in some liver samples is suppressed. Microsomal FMO3 protein content (~ 40-fold) was correlated with FMO3 mRNA levels (r2 = 0.55, p = 0.0010, n= 16), but FMO3 haplotypes did not affect FMO3 mRNA expression (~ 100-fold) under the conditions used. FMO3 mRNA levels were multivariately correlated with trans-acting factors, i.e. hepatic nuclear factor 4 (HNF-4) mRNA and nuclear factor Y box-binding protein (NF-Y) mRNA (r2 = 0.31, p = 0.0017, n = 37). These results suggest that considerable individual differences in FMO3 levels may exist in Japanese livers. The liver-enriched transcription factor HNF-4 appears to be a determinant of FMO3 expression in livers, as well as the ubiquitous factor NF-Y.
Journal: Drug Metabolism and Pharmacokinetics - Volume 24, Issue 3, 2009, Pages 218-225