Ask about this productRelated genes to: FMO3 Blocking Peptide
- Gene:
- FMO3 NIH gene
- Name:
- flavin containing monooxygenase 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-10-16
- Date modifiied:
- 2018-05-03
Related products to: FMO3 Blocking Peptide
Related articles to: FMO3 Blocking Peptide
- Pharmacological and toxicological assessments of a wide array of chemicals typically involve estimating human clearance through allometric extrapolation of in vivo animal data, using empirical compartmental and physiologically based pharmacokinetic (PBPK) models. Parameters for pharmacokinetic absorption, distribution, and metabolic clearance can be calculated and applied to models that replicate observed plasma drug concentration-time profiles. In patients with genetically impaired cytochrome P450 (P450) enzymes who are prescribed only certain drugs, moderate plasma exposure should be noted as a precaution on drug labels, as genetic variants can cause changes in blood concentrations similar to those caused by drug-drug interactions. For new approach methodologies that do not rely on experimental data, human PBPK model input parameters for various compounds have been effectively estimated using in silico-generated chemical descriptors and machine learning tools to assess internal exposure in humans. Many drug oxidations are facilitated by species-dependent and polymorphic P450s and flavin-containing monooxygenases (FMOs). For instance, in rats, the main oxidation product of thalidomide was deactivated 5'-hydroxythalidomide, along with sulfate and glucuronide conjugates. However, the species-specific teratogen thalidomide induces human P450 3A and is activated by P450 3A through the primary human metabolite 5-hydroxythalidomide, leading to its conjugation with nonspecific proteins. The metabolic capacity of polymorphic FMO3 was evaluated based on urine tests for food-derived trimethylamine N-oxide levels. This pharmacokinetic modeling approach, incorporating polymorphic drug-metabolizing enzyme information, could be applied in clinical settings and during computational data-driven evaluations of potential risks associated with a broad spectrum of chemicals. - Source: PubMed
Yamazaki Hiroshi - To characterize protein expression of NLRP3 inflammasome pathway components (NLRP3, TXNIP, ASC, IL-1β, IL-18, Caspase-1) in failing myocardium alongside exploratory mRNA profiling, elucidate their correlation with gut microbiota 16S rRNA gene profiles and the metabolite trimethylamine N-oxide (TMAO), and evaluate how dietary protein restriction and probiotic intervention modulate these pathways to influence heart failure progression. - Source: PubMed
Publication date: 2026/08/18
Li XiaopengYang ChenNie MengmengZhang Yong - Human cells utilize gut microbiota-derived metabolites to control systemic metabolism. Trimethylamine N-oxide (TMAO) is traditionally considered a hepatocyte-derived metabolite from microbial trimethylamine. Here we show that pancreatic β-cells also produce TMAO as an autocrine and intracellular metabolite to maintain β-cell function. β-cells synthesize TMAO via flavin-containing monooxygenase 3 (FMO3), but this machinery deteriorates in humans and rodents under diabetic and ageing conditions. β-cell-specific deletion of FMO3 depletes intracellular TMAO, leading to senescence, inflammation, and defective glucose-stimulated insulin secretion, causing age-dependent glucose intolerance in mice. Loss of FMO3 triggers nuclear factor kappa-B (NF-κB) activation, promoting senescent and inflammatory responses. Mechanistically, TMAO binds to inhibitor of kappa B alpha (IκBα), which inhibits IκBα degradation and NF-κB nuclear translocation, thereby blocking NF-κB-mediated transcription of senescent and inflammatory programs. Replenishment of FMO3 reduces NF-κB activation and senescence in aged human islets. Our findings reveal a protective role of β-cell-derived TMAO against ageing-related β-cell dysfunction. - Source: PubMed
Publication date: 2026/07/27
Wang BaominYang YumeiHo Yuen ManLin HuigeYuan JuntaoLong KekaoCheng Kenneth King YipLi Xiaomu - Diabetes mellitus type 2 (T2DM) is now considered an immunometabolic condition with a long-term low-grade inflammatory state, insulin resistance, and host-microbiome interactions. Emerging evidence suggests that gut microbiota-derived trimethylamine (TMA), its hepatic metabolite trimethylamine N-oxide (TMAO), and IRAK4-mediated innate immune signaling may contribute to metabolic inflammation and insulin resistance. However, direct mechanistic evidence linking these components remains limited, and most available data originate from preclinical studies. Gut microbiota produces TMA based on the nutrients present in the diet, such as choline, betaine, and l-carnitine, which are then oxidized in the liver to trimethylamine N-oxide (TMAO), a metabolite linked to inflammation, metabolic maladaptation, and cardiovascular issues. IRAK4, a signaling mediator of Toll-like receptor and interleukin-1 receptor, may induce NF- kB and MAPK signaling, which may contribute to metaflammation and defective insulin signaling. This overview highlights existing evidence of the TMAIRAK4 axis in the pathogenesis and insulin resistance in T2DM. We discuss current evidence suggesting that TMA/TMAO may influence innate immune signaling and inflammatory pathways associated with insulin resistance. Special attention is given to the interference with the IRSPI3KAkt-pathway by inflammatory signaling mediated by IRAK4. We also consider new treatment approaches, such as IRAK4 inhibitors, control of microbial TMA synthesis, and FMO3-based interventions. Lastly, we underscore important translational issues, such as inconsistency in the evidence about TMAO biology, microbiome diversity, insufficient human validation, and the necessity of multi-omics-based precision methods in patient stratification and personalized treatment. - Source: PubMed
Publication date: 2026/08/13
Sarma Arnabjyoti DevaDevi MoitrayeeKumar DineshChoudhary Neeraj - Metabolic bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective treatment for obesity, yet the molecular mechanisms remain incompletely defined. This study aims to explore the role of hepatic flavin monooxygenase 3 (FMO3) in the metabolic improvements of VSG. - Source: PubMed
Publication date: 2026/08/05
Yan HaiCao ChongTan XiaozhuoHuang XianjueLiu YanyangChu YuxiaoHe MengchengYao QiyuanHua RongShao Yikai