What Is the Role of NADH and FADH2 in Cellular Respiration?

Understanding Electron Carriers

Cellular respiration is a fundamental process where cells convert nutrients, such as glucose, into adenosine triphosphate (ATP), the primary energy currency of the cell. This complex series of reactions powers various cellular activities. Within this intricate process, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) play significant roles, central to efficiently harvesting energy from food breakdown.

NADH and FADH2 function as coenzymes, assisting enzymes in biochemical reactions. They act as molecular shuttles, accepting high-energy electrons and hydrogen ions (protons) from various metabolic pathways. These carriers exist in two forms: an oxidized form (NAD+ and FAD) that accepts electrons, and a reduced form (NADH and FADH2) that carries them. Their ability to switch forms allows them to pick up and donate electrons, making them indispensable for cellular energy production.

Formation of NADH and FADH2

The generation of NADH and FADH2 occurs at specific stages during the breakdown of glucose and other fuel molecules. Glycolysis, the initial stage of glucose metabolism, takes place in the cytoplasm. During this process, a small amount of NADH is formed as glucose is partially broken down, representing an early step in energy conservation.

Following glycolysis, pyruvate undergoes oxidation before entering the citric acid cycle. During pyruvate oxidation, more NADH is produced as pyruvate is converted into acetyl-CoA. This reaction occurs within the mitochondrial matrix, preparing carbon molecules for further oxidation.

The citric acid cycle, also known as the Krebs cycle, operates within the mitochondrial matrix and represents a major hub for nutrient oxidation. In this cyclical series of reactions, acetyl-CoA is completely broken down. The extensive oxidation of carbon atoms in this cycle generates substantial quantities of both NADH and FADH2, capturing energy as high-energy electrons.

Powering the Electron Transport Chain

NADH and FADH2 deliver their high-energy electrons to the electron transport chain (ETC), a series of protein complexes embedded within the inner mitochondrial membrane. This delivery is crucial, as the ETC is where the majority of ATP is generated during cellular respiration. Electrons from NADH are passed to Complex I, while those from FADH2 enter at Complex II.

As electrons move through the protein complexes of the ETC, they release energy. This released energy pumps protons (hydrogen ions) from the mitochondrial matrix into the intermembrane space. This active transport creates a high concentration of protons in the intermembrane space, establishing an electrochemical gradient across the inner mitochondrial membrane.

The proton gradient represents stored potential energy, similar to water behind a dam. Protons then flow back into the mitochondrial matrix through ATP synthase, moving down their concentration gradient like water through a turbine. This proton flow drives ATP synthesis from adenosine diphosphate (ADP) and inorganic phosphate. This process, oxidative phosphorylation, produces approximately 28 to 34 ATP molecules per glucose molecule, vastly exceeding amounts generated in earlier stages. The direct contribution of NADH and FADH2 to this process maximizes energy yield from nutrients.

The Central Role in Cellular Energy

While glycolysis and the citric acid cycle generate some ATP directly through substrate-level phosphorylation, the majority of cellular energy is produced indirectly. This extensive ATP production relies on NADH and FADH2 within the electron transport chain. These electron carriers bridge nutrient breakdown with large-scale ATP synthesis.

Without the efficient electron-carrying capacity of NADH and FADH2, cells could not fully extract chemical energy from food molecules. Their role ensures energy from metabolic reactions is channeled into the highly efficient process of oxidative phosphorylation. This maintains the continuous ATP supply required to sustain all life processes.