The energy required for every function in the body is stored in adenosine triphosphate (ATP). Converting chemical energy from food into this usable cellular currency relies on a system of molecular couriers. Nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) serve this purpose as rechargeable cellular power packs. These coenzymes capture and transport high-energy electrons released during nutrient breakdown. They deliver the vast majority of the energy needed to power the cell’s main ATP production pathway.
Defining the High-Energy Cargo Carriers
The fundamental job of these molecules is rooted in a redox reaction, which involves the transfer of electrons between substances. Nicotinamide adenine dinucleotide exists in an oxidized, or “empty,” state known as NAD+, while its partner, flavin adenine dinucleotide, is “empty” as FAD. When these molecules accept high-energy electrons released from metabolic reactions, they become reduced, transforming into their “loaded” forms: NADH and FADH2.
The oxidized form, NAD+, gains two electrons and a hydrogen ion to become NADH. FAD accepts two electrons and two hydrogen ions to become FADH2. In their reduced states, NADH and FADH2 are chemically unstable, meaning the electrons they carry are held at a high energy level and are ready to be released. This cycling between oxidized and reduced forms allows them to continuously shuttle energy through the cell.
Acquiring Electrons Through Cellular Metabolism
Loading these coenzymes begins as food molecules are broken down inside the cell. The initial stage, glycolysis, occurs in the cytosol and involves splitting a six-carbon glucose molecule into two three-carbon pyruvate molecules. Glycolysis generates a small amount of ATP directly, but its main contribution is the production of NADH.
Pyruvate then moves into the mitochondria, where it undergoes further modification. Each pyruvate is converted into acetyl-CoA (a two-carbon molecule) during pyruvate oxidation, reducing another NAD+ to NADH. Acetyl-CoA then feeds into the next major stage of metabolism.
Acetyl-CoA enters the Citric Acid Cycle (or Krebs Cycle), which completes the breakdown of the food molecule. The cycle systematically removes electrons from acetyl-CoA, oxidizing it to carbon dioxide. With each turn, multiple molecules of NAD+ are reduced to NADH, and FAD is reduced to FADH2. The cumulative output from these three metabolic stages—glycolysis, pyruvate oxidation, and the Citric Acid Cycle—is a large collection of “loaded” NADH and FADH2 molecules, holding the vast majority of the chemical energy.
Powering ATP Production in the Electron Transport Chain
The final job of NADH and FADH2 is to deliver their high-energy cargo to the electron transport chain (ETC), a sequence of protein complexes embedded in the inner mitochondrial membrane. Here, the energy stored in the electrons is converted into ATP. Delivery begins when NADH releases its electrons directly to Complex I, the first major component.
As electrons move through the protein complexes, they gradually release energy. Complexes I, III, and IV harness this energy to act as pumps, actively moving hydrogen ions (protons) from the inner mitochondrial space to the intermembrane space. This establishes a massive concentration difference, creating a high-energy proton gradient across the membrane.
FADH2 performs the same function but takes a different route, delivering its electrons to Complex II and bypassing Complex I. Since Complex II does not function as a proton pump, electrons from FADH2 move fewer protons across the membrane than those from NADH. This difference means each NADH molecule ultimately results in the production of more ATP than each FADH2 molecule.
The potential energy stored in the proton gradient is used to synthesize ATP through oxidative phosphorylation. Protons flow back into the inner space through the specialized enzyme ATP synthase, which acts like a molecular turbine. The force of the proton flow causes the enzyme to spin, driving the reaction that combines adenosine diphosphate (ADP) and inorganic phosphate to produce ATP.