Cellular respiration is the fundamental process organisms use to convert chemical energy stored in nutrient molecules, such as glucose, into a usable form of energy called adenosine triphosphate (ATP). While the initial breakdown of food yields a small amount of this cellular energy currency, the vast majority of ATP is produced through a complex sequence of events. This process relies entirely on two coenzymes: Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (\(\text{FADH}_{2}\)). These molecules serve as the central components required to harvest and deliver the energy that powers nearly all life functions.
NADH and \(\text{FADH}_{2}\): High-Energy Electron Shuttles
These two molecules function as rechargeable batteries within the cell’s energy production pathways, specifically designed to temporarily hold and transport high-energy electrons. Nicotinamide Adenine Dinucleotide, known by its oxidized form \(\text{NAD}^{+}\) and its reduced form NADH, is derived from the B vitamin niacin. When \(\text{NAD}^{+}\) accepts two electrons and one proton from a food molecule, it becomes the high-energy carrier NADH.
Flavin Adenine Dinucleotide, which exists as FAD in its oxidized state, is derived from the B vitamin riboflavin. FAD accepts two electrons and two protons to become its reduced, high-energy form, \(\text{FADH}_{2}\).
NADH and \(\text{FADH}_{2}\) are considered high-energy because the electrons they carry still possess significant potential energy. They are electron carriers that shuttle the energy harvested from the breakdown of carbon-based fuel molecules. This ability to cycle between their oxidized and reduced states allows them to repeatedly participate in the energy transfer process, bridging the gap between fuel breakdown and energy generation.
Generating the Carriers: Production During Early Respiration
The initial phases of cellular respiration are dedicated to stripping electrons from the original fuel molecules and collecting them onto the \(\text{NAD}^{+}\) and FAD carriers. This collection process occurs across three metabolic stages located in both the cell’s cytoplasm and the internal compartment of the mitochondria.
The first stage, glycolysis, breaks down glucose and produces a small yield of NADH molecules in the cytoplasm. The next step, pyruvate oxidation, prepares the broken-down carbon fuel for entry into the main cycle by capturing more electrons onto \(\text{NAD}^{+}\), converting it to NADH inside the mitochondria.
The majority of the electron carriers are generated during the third stage, the Citric Acid Cycle, which fully oxidizes the remaining carbon fuel. Each turn of this cycle yields multiple NADH molecules and one \(\text{FADH}_{2}\) molecule. The accumulated NADH and \(\text{FADH}_{2}\) molecules, loaded with high-energy electrons, represent the bulk of the energy harvested from the food source, setting the stage for the final, most productive phase of cellular respiration.
Delivering Power: The Electron Transport Chain
The definitive function of \(\text{FADH}_{2}\) and NADH is to deliver their stored energy to the Electron Transport Chain (ETC), a series of protein complexes embedded in the inner membrane of the mitochondrion. NADH initiates the energy release by depositing its two high-energy electrons at Complex I, which sits at the beginning of the chain. These electrons are at a higher energy level than those carried by \(\text{FADH}_{2}\).
\(\text{FADH}_{2}\), which holds its electrons at a slightly lower energy level, enters the chain later by delivering its electrons to Complex II. Once transferred, the electrons are passed sequentially from one protein complex to the next along the chain, moving toward the final electron acceptor, oxygen. This movement is energetically favorable, as the electrons fall from a higher to a lower energy state.
The energy released at each major drop in the electron’s energy level is harnessed by Complexes I, III, and IV, which are specialized proton pumps. These pumps use the released energy to actively transport hydrogen ions (protons) from the inner mitochondrial space (the matrix) into the intermembrane space. This continuous pumping action creates a high concentration of protons, establishing a steep electrochemical gradient across the inner membrane. The ETC itself does not synthesize ATP; its sole purpose is to create this high-energy proton gradient, which is the potential energy source for the final step. The electrons are finally accepted by oxygen, which simultaneously combines with protons from the matrix to form water.
The Final Step: ATP Synthesis
The potential energy stored in the proton gradient is converted into chemical energy through a process called chemiosmosis, which is executed by the enzyme ATP synthase. This enzyme is embedded in the inner mitochondrial membrane, spanning the barrier between the high-proton concentration in the intermembrane space and the low-proton concentration in the matrix. The high concentration of protons creates a powerful driving force, causing them to rush back across the membrane and into the matrix, following their concentration gradient.
The only path for these protons to re-enter the matrix is by passing through the channel within the ATP synthase enzyme. The flow of protons through the enzyme causes a portion of the ATP synthase to physically rotate, acting like a molecular turbine. This kinetic energy from the spinning motion is harnessed by the enzyme’s catalytic sites. The mechanical energy forces an inorganic phosphate group onto an adenosine diphosphate (ADP) molecule, successfully synthesizing the high-energy ATP molecule. This final, gradient-driven synthesis of ATP directly utilizes the potential energy established by the electron carriers \(\text{FADH}_{2}\) and NADH.