Flavin adenine dinucleotide- and flavin mononucleotide-dependent enzymes (FAD/FMN-dependent enzymes)

Flavin adenine dinucleotide (FAD)- and flavin mononucleotide (FMN)-dependent enzymes, collectively known as flavoproteins, are a diverse group of enzymes that utilize riboflavin-derived cofactors to catalyze a wide range of essential redox reactions (UniProt, 2024). These enzymes are fundamental to cellular energy production, participating in the mitochondrial electron transport chain, the citric acid cycle, and the beta-oxidation of fatty acids (Macheroux et al., 2011). Beyond metabolic roles, specific flavoenzymes such as monoamine oxidases (MAO) and lysine-specific demethylase 1 (LSD1) are critical for the regulation of neurotransmitters and epigenetic modifications, respectively. Consequently, they serve as vital therapeutic targets in the treatment of neurological disorders like Parkinson's disease and various malignancies (Nature Reviews Drug Discovery, 2018). Pharmacological modulation of these enzymes often involves small molecules that either covalently modify the flavin cofactor or competitively inhibit substrate binding, though selectivity remains a challenge due to the ubiquity of flavin-dependent chemistry in the proteome (StatPearls, 2023).

Other names

FlavoproteinsFlavoenzymesFAD-dependent enzymesFMN-dependent enzymesYellow enzymesRiboflavin-dependent enzymes

Drugs typically act as suicide inhibitors by forming a covalent adduct with the flavin cofactor (FAD or FMN) or as reversible competitive inhibitors that block the substrate binding pocket, thereby preventing the essential redox cycle of the enzyme (StatPearls, 2023; Nature Reviews Drug Discovery, 2018).