Aerobic FAD-dependent dehydrogenases

Aerobic FAD-dependent dehydrogenases (and the closely related oxidases) represent a broad class of flavoenzymes that utilize flavin adenine dinucleotide (FAD) as a redox-active cofactor to catalyze the oxidation of various biological substrates [UniProt, Wikipedia]. These enzymes are characterized by their operation within aerobic environments, where they either utilize molecular oxygen as a terminal electron acceptor—often producing hydrogen peroxide as a byproduct—or transfer electrons directly to the mitochondrial electron transport chain via ubiquinone [PubMed]. This group includes several high-profile therapeutic targets, most notably the monoamine oxidases (MAO-A and MAO-B), which are central to the regulation of neurotransmitters like dopamine and serotonin, and lysine-specific demethylase 1 (LSD1), an epigenetic regulator frequently overexpressed in various cancers [UniProt, NIH]. Clinically, inhibitors of these enzymes are used to treat conditions ranging from depression and Parkinson's disease to acute myeloid leukemia [DrugBank, PubMed]. However, therapeutic intervention must carefully manage risks such as off-target effects on other essential flavoenzymes and the potential for significant drug-food interactions, such as the hypertensive 'cheese effect' associated with traditional MAO inhibitors [StatPearls].

Other names

FAD-dependent oxidoreductasesFlavoprotein dehydrogenasesFAD-dependent amine oxidasesFAD-dependent oxidasesFlavoenzymesGlycerol-3-phosphate dehydrogenase (aerobic)L-lactate dehydrogenase (aerobic)

Inhibition of the FAD-dependent catalytic cycle, preventing the oxidation of specific substrates (e.g., monoamines, methylated histones) and the subsequent reduction of the FAD cofactor [PubMed, DrugBank].