FADH2

FADH2 is the reduced form of flavin adenine dinucleotide (FAD), a redox-active cofactor derived from riboflavin (vitamin B2). In cellular respiration, FADH2 serves as an electron carrier that delivers electrons to the mitochondrial electron transport chain.

FADH2 is produced by several enzymes. In the citric acid cycle, succinate dehydrogenase catalyzes the oxidation of succinate to fumarate with simultaneous reduction of FAD to FADH2. In fatty acid beta-oxidation, acyl-CoA dehydrogenases generate FADH2 as they introduce a double bond into the fatty acyl chain; the electrons from FADH2 are transferred via the ETF/ETF-QO system to ubiquinone. FADH2 donates its electrons to the electron transport chain at the level of ubiquinone (coenzyme Q), via Complex II in mitochondria; this pathway bypasses Complex I.

The electrons ultimately reach Complex III and Complex IV, driving proton pumping and ATP synthesis through oxidative phosphorylation. Because FADH2 enters the chain later than NADH, its oxidation yields fewer ATP molecules—roughly 1.5 ATP per FADH2 under standard conditions, compared with about 2.5–3 ATP per NADH, though exact yields vary with cell conditions and measurement methods.

Flavin adenine dinucleotide is normally bound to specific enzymes as a prosthetic group in many FAD-dependent oxidoreductases, including succinate dehydrogenase and various acyl-CoA dehydrogenases, where it cycles between oxidized and reduced states during catalysis.