Cellular respiration is the process by which living organisms extract usable energy from nutrient molecules, primarily the sugar glucose. This complex biochemical pathway fuels nearly all cellular activities, from muscle contraction and nerve impulses to the synthesis of new proteins and DNA. It converts the potential energy stored in the chemical bonds of food into a universal energy currency called adenosine triphosphate (ATP). The capture of this energy is managed through a sequence of smaller, controlled chemical reactions that maximize efficiency.
Glycolysis in the Cytoplasm
The energy extraction process begins with glycolysis, a sequence of ten reactions that occur in the cytosol of the cell. This initial step is anaerobic, meaning it does not require the presence of oxygen to proceed. During glycolysis, a single six-carbon glucose molecule is broken down into two three-carbon molecules known as pyruvate.
This pathway requires an energy investment of two ATP molecules to prime the glucose structure. Subsequent reactions generate four ATP molecules, resulting in a net gain of two ATP molecules directly produced. This stage also captures high-energy electrons by reducing two molecules of the carrier \(\text{NAD}^+\) into \(\text{NADH}\), which will be utilized later.
Pyruvate Conversion in the Mitochondrion
Following glycolysis, the two molecules of pyruvate move from the cytosol into the mitochondrion. This transition phase, sometimes called pyruvate oxidation, acts as a bridge connecting the first stage to the main energy-generating cycles. Pyruvate must cross the inner and outer mitochondrial membranes to reach the matrix, the innermost compartment of the organelle.
Once inside the matrix, an enzyme complex catalyzes a three-step reaction to convert each three-carbon pyruvate molecule into a two-carbon compound called Acetyl-CoA. This conversion involves the removal of a carboxyl group, which is released as a molecule of carbon dioxide. The remaining two-carbon fragment is oxidized, reducing one \(\text{NAD}^+\) to \(\text{NADH}\), before being attached to Coenzyme A to form Acetyl-CoA.
The Citric Acid Cycle
The Acetyl-CoA molecules enter the Citric Acid Cycle, a metabolic loop that takes place entirely within the mitochondrial matrix. This cycle, also known as the Krebs cycle, completes the systematic oxidation of the carbon atoms that were originally part of the glucose molecule. Acetyl-CoA joins with the four-carbon molecule oxaloacetate to form citrate, initiating the cycle.
Through a series of eight enzyme-catalyzed steps, the citrate molecule is progressively dismantled. The primary purpose of this cycle is to harvest high-energy electrons. For each turn, two molecules of carbon dioxide are released, accounting for the complete breakdown of Acetyl-CoA. The process reduces three \(\text{NAD}^+\) molecules to \(\text{NADH}\) and one \(\text{FAD}\) molecule to \(\text{FADH}_2\), which carry the chemical energy needed for the final stage.
Oxidative Phosphorylation and ATP Production
The final and most productive stage of cellular respiration is oxidative phosphorylation, situated on the inner mitochondrial membrane. This stage consists of two coupled processes: the Electron Transport Chain (ETC) and chemiosmosis. The electron carriers \(\text{NADH}\) and \(\text{FADH}_2\), generated in the previous steps, deposit their high-energy electrons at protein complexes embedded in the membrane.
As electrons are passed sequentially down the chain, the energy released is used to actively pump protons (\(\text{H}^+\) ions) from the mitochondrial matrix into the intermembrane space. This pumping action establishes a high concentration of protons, creating an electrochemical gradient across the inner membrane. This gradient stores potential energy.
The protons then flow back into the matrix, moving down their concentration gradient through a specialized enzyme complex called ATP synthase. The flow of protons couples the energy of the gradient to the phosphorylation of ADP, synthesizing large amounts of ATP in a process known as chemiosmosis. Oxygen acts at the end of the chain as the final electron acceptor, combining with the electrons and protons to form water, which is why this entire process is strictly aerobic.
Net Energy Output Summary
The total energy yield from the complete breakdown of one glucose molecule is the sum of the small amounts generated directly and the large amount produced indirectly. Glycolysis provides a net of two ATP molecules through substrate-level phosphorylation. The Citric Acid Cycle also directly yields two ATP molecules, or the equivalent GTP, per glucose molecule.
The vast majority of the energy is produced during oxidative phosphorylation, where the \(\text{NADH}\) and \(\text{FADH}_2\) molecules power the proton gradient. Due to the energy stored in these carriers, oxidative phosphorylation generates approximately 30 to 34 ATP molecules. The overall process converts the potential chemical energy of glucose into a total of about 30 to 38 ATP molecules.