Cellular respiration is the process cells use to convert the chemical energy stored in food molecules, primarily glucose, into adenosine triphosphate (ATP). ATP provides the energy currency for almost all cellular activities, from muscle contraction to nerve impulse transmission. The overall chemical reaction shows that glucose and oxygen are consumed to produce carbon dioxide, water, and energy. This process unfolds across two main locations: the initial step occurs in the cytoplasm, while the subsequent stages take place inside the mitochondria.
Glycolysis
The first stage is Glycolysis, which literally means “splitting sugar.” This process takes place in the cytoplasm, making it a universal energy pathway across all living organisms. Glycolysis begins with a single six-carbon glucose molecule and breaks it down into two three-carbon molecules of pyruvate.
This initial breakdown requires an investment of two ATP molecules to start the reaction. Later steps generate four ATP molecules, resulting in a net gain of two ATP per glucose. Glycolysis does not require oxygen, allowing it to function under both aerobic and anaerobic conditions. The process also produces two molecules of the high-energy electron carrier NADH.
Pyruvate Oxidation
Following glycolysis, the two pyruvate molecules undergo a transition step known as Pyruvate Oxidation before entering the final stages of respiration. This occurs as pyruvate moves from the cytoplasm into the mitochondrial matrix in eukaryotic cells. The three-carbon pyruvate molecule is modified by the pyruvate dehydrogenase complex.
During this conversion, a carboxyl group is removed from each pyruvate and released as carbon dioxide. The remaining two-carbon fragment is oxidized, and the lost electrons are captured by \(\text{NAD}^+\) to form NADH. Finally, the two-carbon unit attaches to Coenzyme A, forming Acetyl-CoA, which fuels the next major cycle.
The Citric Acid Cycle
The third stage, the Citric Acid Cycle (or Krebs Cycle), operates as a closed loop within the mitochondrial matrix. The cycle begins when the two-carbon Acetyl-CoA combines with a four-carbon acceptor molecule, oxaloacetate, to form the six-carbon molecule, citrate. The oxaloacetate is regenerated at the end of the cycle to accept a new Acetyl-CoA.
The two carbons from the Acetyl-CoA are completely oxidized and released as two molecules of carbon dioxide. The primary function of the cycle is the systematic harvesting of high-energy electrons, not the direct production of ATP. Each turn generates three \(\text{NADH}\) and one \(\text{FADH}_2\) molecule, which are the cell’s main energy carriers. Only a small amount of direct energy is produced, yielding one molecule of \(\text{ATP}\) or \(\text{GTP}\) per cycle.
Oxidative Phosphorylation
Oxidative Phosphorylation is the fourth stage, yielding the vast majority of ATP, and takes place on the inner mitochondrial membrane. This stage combines two linked processes: the Electron Transport Chain (\(\text{ETC}\)) and Chemiosmosis. The \(\text{ETC}\) begins when \(\text{NADH}\) and \(\text{FADH}_2\) drop off their high-energy electrons at a series of protein complexes embedded in the membrane.
As electrons move along the chain, the released energy pumps hydrogen ions (protons) from the matrix into the intermembrane space. This active pumping establishes a powerful electrochemical gradient. Chemiosmosis harnesses this potential energy when protons flow back into the matrix through the channel-forming enzyme \(\text{ATP}\) Synthase. The flow of protons causes \(\text{ATP}\) Synthase to rotate, providing the mechanical energy to attach a phosphate group to \(\text{ADP}\), generating large amounts of \(\text{ATP}\). The process is termed “oxidative” because oxygen is the final electron acceptor at the end of the \(\text{ETC}\), combining with electrons and protons to form water.
Net Energy Production and Regulation
The four stages of cellular respiration work together to achieve an efficient conversion of chemical energy. Fully oxidizing one glucose molecule through the aerobic pathway yields approximately 30 to 32 \(\text{ATP}\) molecules. This estimate relies heavily on the large yield from oxidative phosphorylation, far exceeding the two net \(\text{ATP}\) molecules generated by anaerobic respiration (glycolysis alone).
The entire metabolic pathway is tightly controlled to maintain cellular energy balance. Regulation is achieved through feedback inhibition. For example, a high concentration of \(\text{ATP}\) signals the process to slow down. Conversely, a buildup of \(\text{ADP}\), which indicates high energy demand, signals the enzymes to speed up \(\text{ATP}\) production.