Cellular respiration is the complex set of metabolic reactions that living organisms use to convert chemical energy stored in food molecules into a usable form of energy called adenosine triphosphate (ATP). ATP powers nearly all cellular activities, from muscle contraction to the synthesis of new molecules. The complete breakdown of glucose in the presence of oxygen can be summarized by the equation: Glucose plus Oxygen yields Carbon Dioxide, Water, and Energy. This controlled release of energy occurs through a series of four interconnected stages, which efficiently harvest the energy stored in the chemical bonds of glucose.
Glycolysis: Starting the Breakdown
Glycolysis is the first stage of glucose breakdown and takes place outside the mitochondria, within the cell’s cytoplasm. This initial set of reactions is considered an anaerobic process because it does not require oxygen to proceed. The main action involves the splitting of a single six-carbon glucose molecule into two separate three-carbon molecules known as pyruvate.
The process begins with an investment of two ATP molecules to destabilize the glucose structure, which primes the molecule for splitting. A small energy payoff is then generated through substrate-level phosphorylation, a mechanism that directly transfers a phosphate group to adenosine diphosphate (ADP). This generates a net total of two ATP molecules and two molecules of nicotinamide adenine dinucleotide in its reduced form, or NADH. In aerobic conditions, the resulting pyruvate molecules must next enter the mitochondria.
Pyruvate Oxidation: The Transition Step
The two pyruvate molecules generated during glycolysis must undergo a preparatory step before they can fully enter the main energy-generating cycle. This transitional stage, known as pyruvate oxidation, occurs as the pyruvate is actively transported from the cytoplasm into the mitochondrial matrix. The conversion is carried out by a large enzyme complex, which facilitates a series of reactions.
During this process, a carboxyl group is removed from each pyruvate and released as a molecule of carbon dioxide. The remaining two-carbon unit is then combined with a molecule called Coenzyme A, forming Acetyl-CoA. This reaction also produces another molecule of NADH. Acetyl-CoA now serves as the primary fuel input for the subsequent cyclical pathway inside the mitochondrion.
The Citric Acid Cycle
The Citric Acid Cycle, also widely known as the Krebs cycle, occurs within the mitochondrial matrix. This sequence of eight reactions is cyclical because the final product is the same molecule that accepts the incoming Acetyl-CoA at the beginning of the cycle. The Acetyl-CoA combines with a four-carbon compound, oxaloacetate, to form the six-carbon molecule citrate, which gives the cycle its name.
The primary function of this cycle is not to produce large amounts of ATP directly, but rather to systematically extract high-energy electrons from the breakdown products of glucose. As the citrate molecule is progressively oxidized through the cycle, its chemical energy is transferred to electron carrier molecules. For every turn of the cycle, three molecules of NADH and one molecule of FADH2 are produced.
Each two-carbon Acetyl-CoA that enters the cycle is completely oxidized, resulting in the release of two molecules of carbon dioxide. The cycle also yields one molecule of ATP or a related energy molecule, GTP, per turn, which is another example of substrate-level phosphorylation. Since two molecules of Acetyl-CoA are formed from the initial glucose molecule, the cycle turns twice. The true energy yield of the cycle is stored almost entirely within the numerous NADH and FADH2 molecules, which will proceed to the final stage.
Oxidative Phosphorylation: Maximum Energy Yield
Oxidative phosphorylation is the final stage of cellular respiration and is responsible for generating the majority of the cell’s ATP. This process takes place on the inner membrane of the mitochondrion and is dependent on the presence of oxygen. It consists of two tightly coupled components: the Electron Transport Chain (ETC) and chemiosmosis.
The electron carriers, NADH and FADH2, harvested from the previous stages, donate their high-energy electrons to the protein complexes embedded in the inner mitochondrial membrane. As these electrons are passed down the chain from one complex to the next, energy is released in a stepwise manner. This released energy is used to actively pump hydrogen ions, or protons, from the mitochondrial matrix into the intermembrane space.
The continuous pumping of protons creates a high concentration gradient across the inner membrane, similar to water building up behind a dam. This electrochemical gradient represents a form of potential energy that the cell can harness. At the end of the ETC, oxygen serves as the terminal electron acceptor, combining with the electrons and protons to form water.
The stored energy in the proton gradient is then used in the process of chemiosmosis. Protons flow back into the matrix through a specialized enzyme complex called ATP synthase. The force of the proton flow causes the ATP synthase enzyme to rotate, physically driving the synthesis of ATP from ADP and inorganic phosphate. This mechanism produces approximately 30 to 32 ATP molecules per glucose, representing the maximum energy yield from cellular respiration.