FADdependent

FADdependent, also written FAD-dependent, is an adjective used to describe enzymes or reactions that require flavin adenine dinucleotide (FAD) as a cofactor. FAD is a redox-active nucleotide derived from riboflavin (vitamin B2) and functions in flavoproteins as a prosthetic group or tightly bound cofactor. In these enzymes, FAD cycles between oxidized FAD and reduced FADH2 states as it shuttles electrons during catalysis. FAD can participate in one-electron and two-electron transfers, enabling diverse chemistry including dehydrogenation, hydroxylation, and oxidative demethylation. In many cases, FAD is bound tightly to the enzyme, sometimes covalently, stabilizing reactive intermediates and enabling rapid electron transfer to downstream acceptors such as ubiquinone, molecular oxygen, or NAD+.

Typical examples include the flavoprotein oxidoreductases and monooxygenases. In the citric acid cycle, succinate dehydrogenase (Complex II) uses FAD as its initial electron acceptor. Fatty acid beta-oxidation employs acyl-CoA dehydrogenases that transfer electrons to the electron-transferring flavoprotein via FAD. Flavoprotein monooxygenases, such as flavin-containing monooxygenases, utilize FAD to activate O2 for substrate hydroxylation. Other FAD-dependent enzymes include monoamine oxidases, some amino acid oxidases, and various oxidases involved in detoxification.

Biosynthesis of FAD proceeds from riboflavin in cells through riboflavin kinase, which forms FMN, followed by FAD synthetase. Diet and metabolic state influence flavoprotein activity, and impairment of FAD-dependent enzymes can contribute to metabolic disorders.