Adenosine triphosphate (ATP) is the cell’s primary mechanism for fueling nearly all its activities. Known as the energy currency of the cell, ATP stores readily available chemical energy within its bonds. Cellular respiration is a fundamental metabolic process that systematically breaks down nutrient molecules, most often glucose, converting the stored chemical energy into usable ATP. This complex process is broadly categorized into three interconnected stages: glycolysis, the citric acid cycle, and oxidative phosphorylation. These stages function sequentially, each step extracting energy from the initial glucose molecule to maximize the final yield.
The Initial Energy Investment: Glycolysis
Glycolysis, the first stage, takes place within the cytosol outside the mitochondria. This metabolic pathway begins with a single six-carbon glucose molecule, which is broken down into two molecules of a three-carbon compound called pyruvate. The process involves an initial energy-spending phase, consuming two ATP molecules to destabilize the glucose and prepare it for splitting.
Following this investment, the pathway enters an energy-generating phase, producing a total of four ATP molecules. This direct synthesis of ATP is known as substrate-level phosphorylation, involving the transfer of a phosphate group directly to adenosine diphosphate (ADP). The result is a net gain of two ATP molecules per glucose molecule. Additionally, glycolysis generates two molecules of the high-energy electron carrier NADH, which holds electrons for greater ATP production later in the process.
Fueling the Cycle: The Citric Acid Cycle
The two pyruvate molecules generated by glycolysis are transported into the mitochondrial matrix. Here, each pyruvate is converted into acetyl coenzyme A (acetyl-CoA) in a transitional step that produces one molecule of NADH and releases carbon dioxide. Acetyl-CoA then enters the citric acid cycle, also known as the Krebs cycle.
The cycle’s primary function is to completely oxidize the carbon atoms from acetyl-CoA, harvesting their energy in the form of high-energy electron carriers. Since there are two turns per glucose molecule, the cycle generates six molecules of NADH and two molecules of FADH₂. The cycle also produces one molecule of ATP directly through substrate-level phosphorylation per turn. The energy stored in these electron carriers represents the vast majority of the glucose molecule’s remaining usable energy.
The Major Production Line: Oxidative Phosphorylation
Oxidative phosphorylation, the final and most productive stage, takes place on the inner mitochondrial membrane. This process consists of two coupled components: the electron transport chain (ETC) and chemiosmosis. The ETC is a series of protein complexes that accept high-energy electrons from the NADH and FADH₂ carriers produced earlier.
As electrons pass along the chain, the released energy pumps hydrogen ions (protons) from the mitochondrial matrix into the intermembrane space. This continuous pumping establishes a high concentration of protons, creating an electrochemical gradient. This gradient stores significant potential energy, which is then utilized by chemiosmosis.
The protons flow back into the matrix through ATP synthase, a molecular machine embedded in the inner membrane. The proton flow causes the ATP synthase to rotate, providing the energy needed to catalyze the phosphorylation of ADP, synthesizing large quantities of ATP. This process accounts for approximately 90% of all ATP produced from glucose oxidation. The spent electrons are finally accepted by oxygen, resulting in the formation of water, which is why this stage is strictly aerobic.
Total Energy Accounting
Oxidative phosphorylation is the primary source of cellular energy. The initial two stages, glycolysis and the citric acid cycle, contribute a total of four ATP molecules directly via substrate-level phosphorylation. The remaining ATP is generated indirectly by the electron carriers, which power the final stage.
The estimated total ATP yield from the complete oxidation of one glucose molecule falls within a range of 30 to 32 ATP molecules. This range exists because the energy yield of the electron carriers is not fixed and varies depending on how electrons are transported into the mitochondria. Furthermore, some of the proton gradient’s energy is used for other cellular activities, slightly reducing the maximum theoretical output. The indirect production from oxidative phosphorylation is responsible for approximately 26 to 28 ATP molecules, demonstrating its dominant role in energy generation.