Aerobic respiration is the primary process by which cells generate energy, in the form of adenosine triphosphate (ATP), from glucose in the presence of oxygen. This complex, multi-step process is fundamental to life, powering nearly all cellular activities. While glucose and oxygen are recognized as key inputs, two often-overlooked molecules, nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), are central to this energy production.
NAD and FAD Explained
NAD and FAD are coenzymes, non-protein organic molecules that assist enzymes in catalyzing various biochemical reactions. NAD is derived from niacin (vitamin B3), while FAD originates from riboflavin (vitamin B2). Their fundamental role involves acting as electron carriers, much like rechargeable batteries. They accept high-energy electrons and hydrogen ions from metabolic reactions, becoming reduced in the process.
NAD exists in an oxidized form, NAD+, and a reduced form, NADH. When NAD+ accepts two electrons and one hydrogen ion, it transforms into NADH, releasing the other hydrogen ion into solution. Similarly, FAD, in its oxidized state, accepts two hydrogen atoms, each with one electron, to become FADH2. These reduced forms, NADH and FADH2, temporarily store the potential energy carried by the electrons, which is crucial for subsequent energy-generating steps.
Electron Carriers in Glycolysis and the Krebs Cycle
NAD+ and FAD begin their electron-collecting journey in the initial stages of aerobic respiration, glycolysis and the Krebs cycle. Glycolysis, the first stage, occurs in the cytoplasm of the cell. During this process, glucose is broken down into smaller molecules. A key step in glycolysis involves the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, where NAD+ accepts electrons and a hydrogen ion, becoming NADH. For each molecule of glucose processed, glycolysis yields two molecules of NADH.
Following glycolysis, the products enter the Krebs cycle, also known as the citric acid cycle, which takes place within the mitochondrial matrix. Here, the carbon compounds derived from glucose are further broken down. As these compounds are oxidized, amounts of NAD+ and FAD are reduced, forming NADH and FADH2. For each turn of the Krebs cycle, three molecules of NADH and one molecule of FADH2 are produced. Since one glucose molecule leads to two turns of the Krebs cycle, a total of six NADH and two FADH2 molecules are generated from this stage.
Powering the Electron Transport Chain
The NADH and FADH2 molecules generated in earlier stages play a crucial role in the final and most energy-yielding phase of aerobic respiration: the electron transport chain (ETC). This system is located within the inner mitochondrial membrane. NADH and FADH2 deliver their high-energy electrons to the protein complexes embedded in this membrane.
As these electrons move sequentially through the series of protein complexes in the ETC, energy is progressively released. This released energy is harnessed to pump protons (hydrogen ions) from the mitochondrial matrix into the intermembrane space. This action creates a high concentration of protons in the intermembrane space, establishing an electrochemical gradient known as the proton motive force. The potential energy stored in this gradient is then utilized by an enzyme called ATP synthase. Protons flow back into the mitochondrial matrix through ATP synthase, and this movement drives the enzyme to synthesize large quantities of ATP through a process called oxidative phosphorylation.
NADH typically donates its electrons at an earlier point in the ETC (Complex I) compared to FADH2 (Complex II). Because NADH’s electrons enter at an earlier stage, they contribute to the pumping of more protons across the membrane than FADH2’s electrons. Consequently, each NADH molecule generally leads to the production of approximately 2.5 ATP molecules, while each FADH2 molecule yields about 1.5 ATP molecules.
The Indispensable Role of NAD and FAD
NAD and FAD are essential for aerobic respiration. These coenzymes act as intermediaries, collecting high-energy electrons during glucose breakdown. Without the continuous cycling of NAD+ to NADH and FAD to FADH2, and their subsequent delivery of electrons to the electron transport chain, most ATP produced during aerobic respiration would not be possible. Their role as the link between the initial stages of glucose breakdown and the final energy generation means that cellular energy production depends on their presence and function.