Редактирование: FMO3 (раздел)

==Publications==

{{medline-entry
|title=Genetic and Nongenetic Factors Associated with Protein Abundance of Flavin-Containing Monooxygenase 3 in Human Liver.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28819071
|abstract=Hepatic flavin-containing mono-oxygenase 3 ([[FMO3]]) metabolizes a broad array of nucleophilic heteroatom (e.g., [i]N[/i] or [i]S[/i])-containing xenobiotics (e.g., amphetamine, sulindac, benzydamine, ranitidine, tamoxifen, nicotine, and ethionamide), as well as endogenous compounds (e.g., catecholamine and trimethylamine). To predict the effect of genetic and nongenetic factors on the hepatic metabolism of [[FMO3]] substrates, we quantified [[FMO3]] protein abundance in human liver microsomes (HLMs; [i]n[/i] = 445) by liquid chromatography-tandem mass chromatography proteomics. Genotyping/gene resequencing, mRNA expression, and functional activity (with benzydamine as probe substrate) of [[FMO3]] were also evaluated. [[FMO3]] abundance increased 2.2-fold (13.0 ± 11.4 pmol/mg protein vs. 28.0 ± 11.8 pmol/mg protein) from neonates to adults. After 6 years of age, no significant difference in [[FMO3]] abundance was found between children and adults. Female donors exhibited modestly higher mRNA fragments per kilobase per million reads values (139.9 ± 76.9 vs. 105.1 ± 73.1; [i]P[/i] < 0.001) and protein [[FMO3]] abundance (26.7 ± 12.0 pmol/mg protein vs. 24.1 ± 12.1 pmol/mg protein; [i]P[/i] < 0.05) compared with males. Six single nucleotide polymorphisms (SNPs), including rs2064074, rs28363536, rs2266782 (E158K), rs909530 (N285N), rs2266780 (E308G), and rs909531, were associated with significantly decreased protein abundance. [[FMO3]] abundance in individuals homozygous and heterozygous for haplotype 3 (H3), representing variant alleles for all these SNPs (except rs2066534), were 50.8% ([i]P[/i] < 0.001) and 79.5% ([i]P[/i] < 0.01), respectively, of those with the reference homozygous haplotype (H1, representing wild-type). In summary, [[FMO3]] protein abundance is significantly associated with age, gender, and genotype. These data are important in predicting [[FMO3]]-mediated heteroatom-oxidation of xenobiotics and endogenous biomolecules in the human liver.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Child
* Child, Preschool
* Cohort Studies
* Female
* Genotype
* Humans
* Infant
* Infant, Newborn
* Liver
* Male
* Middle Aged
* Oxygenases
* RNA, Messenger
* Sex Characteristics
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697103
}}