Should We Teach FAD(H 2 ) Is an Electron Carrier or a Cocatalyst, and Why Does It Matter?

High Resolution Image Download MS PowerPoint Slide Students of biochemistry are routinely taught that there are two primary electron carriers in catabolism: nicotinamide adenine dinucleotide (NAD + /NADH) and flavin adenine dinucleotide (FAD/FADH 2 ). In fact, the latter is not at all a “carrier” in the sense of a diffusible coenzyme that “carries” electrons. Rather, it is a tightly bound cofactor that catalyzes intraenzyme electron transfers. Yet we persist in presenting FADH 2 as an intermediate in aerobic respiration, and overuse of this approximation, coupled with ambiguous diagrams and descriptions, can lead to propagation of serious misconceptions about respiration. I discuss the appeal and limitations of the narrative that FAD(H 2 ) is an electron carrier, contrast it with an alternate conception that disposes of FADH 2 “yields” entirely, and suggest a hybrid conceptualization of aerobic respiration that emphasizes the various multienzyme pathways that supply the electron transport chain via FAD(H 2 ). This latter model preserves the notion of FADH 2 “yields” and the simplicity of two classes of electrons, while minimizing the risk of misconceptions associated with treating FAD(H 2 ) as a reactant or product.