Target intelligence / Profile preview

Dimethylaniline monooxygenase [N-oxide-forming] 4 (FMO4)

Target
FMO4
Molecular classification
Enzyme, Flavin-containing monooxygenase family, NADPH-dependent flavoenzyme
01

Overview

Dimethylaniline monooxygenase [N-oxide-forming] 4 (FMO4) is a member of the flavin-containing monooxygenase family of NADPH-dependent enzymes found predominantly in the adult liver and involved in the oxidative metabolism of xenobiotics, drugs, and dietary compounds, especially those featuring nucleophilic nitrogen or sulfur centers[1][5]. It facilitates the N-oxidation of trimethylamine and similar substrates, converting them into more hydrophilic compounds for excretion[1]. FMO4 is closely related to other FMOs (such as FMO2 and FMO3) but has distinct expression and substrate preferences. It participates in cellular processes relevant to cancer progression, oxidative stress response, and calcium homeostasis (shown in model organisms)[1][2][4]. Downregulation of FMO4 is associated with cancer, and its expression profile is under investigation both as a prognostic marker and as a potential therapeutic target in oncology[4]. The family, including FMO4, can impact variability in drug metabolism and propensity for adverse drug reactions due to individual differences in gene expression and activity[3][5].

Other names
Flavin-containing monooxygenase 4Dimethylaniline oxidase 4Hepatic flavin-containing monooxygenase 4FMO 4Dimethylaniline monooxygenase [N-oxide-forming] 4FMO2 (note: FMO2 is technically a distinct family member, sometimes confused)Flavin containing monooxygenase 4
02

Mechanism of action

NADPH-dependent oxidation of substrates at nucleophilic heteroatom centers (N or S), generating N-oxides or S-oxides and facilitating their excretion. Stabilizes C4a-hydroperoxyflavin intermediate for oxygenation reactions.

03

Biological functions

Xenobiotic metabolismN-oxidation of drugs and dietary compounds (e.g., trimethylamine)Detoxification of soft nucleophilic heteroatom centers (nitrogen, sulfur)Regulation of oxidative stress responseCalcium homeostasis (in C. elegans orthologs)Modulation of longevity and stress resistance (evidence from model organisms)
04

Disease associations

Cancer (particularly hepatocellular carcinoma and uterine cervical preneoplastic lesions; implicated as a prognostic biomarker and potential therapeutic target)Trimethylaminuria (fish odor syndrome, via related FMO3 deficiency)Other: Implicated in drug metabolism–related diseases due to variability in metabolic capacity
05

Safety considerations

Variability in FMO expression and activity may influence drug response and toxicityGenetic polymorphisms (paralleling FMO3) can lead to metabolic insufficiencies (e.g., fish odor syndrome); not specifically documented for FMO4 but plausible for family membersRole in reactive oxygen species (ROS) generation–potential for oxidative stress
06

Interacting drugs

Drugs and xenobiotics with “soft nucleophile” atoms (nitrogen or sulfur), such as trimethylamine, drugs metabolized in the liver

1 more in the full profile.

07

Biomarkers

Decreased FMO4 expression is a negative prognostic biomarker for hepatocellular carcinomaDownregulation in HPV-positive cervical lesions suggests a marker for progressionNo standardized patient selection biomarker for drugs based solely on FMO4

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