Flavin Adenine Dinucleotide (FADH2) is a molecule that plays a central role in the energy generation process of cells. It acts as a temporary carrier, storing high-energy electrons harvested from the breakdown of nutrients. These captured electrons are then transported to the final stage of cellular respiration, where their energy is converted into adenosine triphosphate (ATP), the cell’s primary energy currency.
Defining Flavin Adenine Dinucleotide
The molecule FADH2 is the reduced form of the coenzyme Flavin Adenine Dinucleotide (FAD). This coenzyme is derived from riboflavin, which is commonly known as Vitamin B2, an essential nutrient that humans must obtain through their diet. FAD consists of two main parts: an adenine nucleotide and a flavin mononucleotide, which are linked together by phosphate groups.
FAD functions as a cofactor, meaning it must be present for certain enzymes to carry out their reactions. In its oxidized state (FAD), the molecule is ready to accept two high-energy electrons and two protons (hydrogen ions). Once it accepts these particles, it becomes chemically reduced, transforming into its active, high-energy form, FADH2. This reduction process makes FADH2 a temporary storage unit for the energy released during the catabolism of carbohydrates and fats.
The Metabolic Pathways that Produce FADH2
The primary source of FADH2 production occurs within the mitochondrial matrix during the Citric Acid Cycle. This cycle is a central metabolic hub that processes the remnants of carbohydrates, fats, and proteins. During the conversion of the molecule succinate to fumarate within this cycle, the enzyme succinate dehydrogenase is responsible for the transfer of electrons and protons.
The FAD molecule is actually an integral part of the succinate dehydrogenase enzyme complex, where it is covalently bound. When the reaction occurs, the FAD is reduced to FADH2, capturing the energy from the succinate molecule. FADH2 is also generated during the beta-oxidation of fatty acids, a process that breaks down fats into smaller units.
Delivering Electrons for ATP Synthesis
The purpose of FADH2 is to deliver its stored high-energy electrons to the Electron Transport Chain (ETC), a series of protein complexes located in the inner mitochondrial membrane. This transfer is the first step in a process called oxidative phosphorylation, which generates nearly all of the cell’s ATP. FADH2 deposits its electrons at Complex II of the ETC, which is the same succinate dehydrogenase enzyme that produced it.
As FADH2 transfers its electrons to Complex II, they are passed along to other carriers within the membrane, such as ubiquinone, also known as Coenzyme Q. The movement of these electrons through the subsequent complexes of the ETC releases energy. This energy is used to pump protons (hydrogen ions) from the mitochondrial matrix into the intermembrane space, creating a high concentration gradient. This proton gradient is similar to water building up behind a dam, representing a powerful form of stored energy. The flow of these protons back into the matrix through a turbine-like enzyme called ATP synthase directly drives the synthesis of ATP.
Key Differences Between FADH2 and NADH
FADH2 often works alongside a more abundant electron carrier, Nicotinamide Adenine Dinucleotide (NADH), but they differ in three important ways.
Production and Source
The first difference is their primary source and production levels. While FADH2 is largely restricted to the Citric Acid Cycle and beta-oxidation, NADH is produced in greater quantities throughout glycolysis, the Citric Acid Cycle, and the preparatory step before the cycle. This means a cell typically generates more NADH than FADH2.
ETC Entry Point
The second distinction is their entry point into the Electron Transport Chain. NADH deposits its electrons at Complex I, which is the very beginning of the chain. FADH2, however, deposits its electrons later at Complex II, effectively bypassing Complex I. This difference in entry point is significant because Complex I is one of the ETC complexes that actively pumps protons across the membrane.
ATP Yield
This earlier entry allows NADH’s electrons to drive the pumping of protons at three different complexes, while FADH2’s electrons only drive proton pumping at the two later complexes (Complexes III and IV). The final difference is the resulting ATP yield: because FADH2 enters later and misses the proton-pumping action of Complex I, it generates less usable energy. Specifically, each molecule of FADH2 typically yields about 1.5 molecules of ATP, whereas each molecule of NADH can generate approximately 2.5 molecules of ATP.