Glycolysis is a foundational metabolic pathway that begins the breakdown of glucose to extract energy for the cell. Although often mistakenly associated with the mitochondria due to its connection to cellular respiration, glycolysis does not occur there. It is the initial step in energy production that takes place in a different cellular compartment.
Where Glycolysis Actually Occurs
Glycolysis occurs exclusively in the cytosol, the fluid that fills the interior of the cell outside of the organelles. The ten enzymes required for glycolysis are freely dissolved within this cellular space. Since all necessary components are present in the cytosol, the process occurs without needing to cross any organelle membranes.
The process begins with one six-carbon molecule of glucose. The cell must first invest two molecules of \(\text{ATP}\) to destabilize the glucose molecule and prepare it for cleavage. This initial investment traps the glucose inside the cell and makes it chemically ready for subsequent reactions.
The pathway then breaks the six-carbon sugar into two three-carbon molecules called pyruvate. In this phase, the pathway generates four \(\text{ATP}\) molecules and two molecules of \(\text{NADH}\), an electron-carrying molecule. This results in a net gain of two \(\text{ATP}\) and two \(\text{NADH}\) per glucose molecule.
Glycolysis is an anaerobic process, meaning it does not require oxygen to proceed. This capability allows cells to quickly generate a small amount of energy even when oxygen supplies are low. Due to its location and independence from oxygen, glycolysis is considered an evolutionarily ancient metabolic pathway.
The Fate of Pyruvate
The two pyruvate molecules produced in the cytosol proceed down one of two paths, depending on the availability of oxygen. If oxygen is scarce, such as during intense muscle exertion, the cell switches to fermentation. This anaerobic pathway converts pyruvate into lactate in humans, which regenerates the \(\text{NAD}^{+}\) needed to keep glycolysis running.
If oxygen is plentiful, the pyruvate is actively transported into the mitochondrial matrix. This transport links the cytosolic process of glycolysis to the energy systems inside the mitochondrion. Once inside the matrix, pyruvate undergoes pyruvate oxidation, sometimes called the link reaction.
In this reaction, a large enzyme complex removes a carbon dioxide molecule from each three-carbon pyruvate. The remaining two-carbon unit attaches to Coenzyme A, forming acetyl-CoA. This step also produces another molecule of \(\text{NADH}\), which contributes to later energy generation. The acetyl-CoA is then ready to enter the core energy-producing cycle of the mitochondria.
Generating Maximum Energy
The mitochondrial matrix, where the acetyl-CoA resides, is the location for the Citric Acid Cycle, also known as the Krebs Cycle. This cyclical pathway oxidizes the two-carbon acetyl-CoA, releasing two carbon dioxide molecules. The cycle’s function is not to produce large amounts of \(\text{ATP}\) directly, as it only generates one molecule of \(\text{ATP}\) (or \(\text{GTP}\)) per turn.
The main yield of the Krebs Cycle is the capture of high-energy electrons onto carrier molecules. The cycle produces several molecules of \(\text{NADH}\) and \(\text{FADH}_{2}\), which are loaded with electrons extracted from the acetyl-CoA. These molecules serve as the energy currency for the next, most productive phase of cellular respiration.
The \(\text{NADH}\) and \(\text{FADH}_{2}\) deliver their electrons to the Electron Transport Chain (\(\text{ETC}\)), a series of protein complexes in the inner mitochondrial membrane. As electrons pass down the chain, their energy pumps hydrogen ions into the space between the inner and outer membranes, creating a concentration gradient. This gradient represents stored potential energy.
The flow of these hydrogen ions back into the matrix through \(\text{ATP}\) synthase drives the synthesis of a large quantity of \(\text{ATP}\) via oxidative phosphorylation. This final stage is strictly aerobic, requiring oxygen to act as the final electron acceptor, forming water. The small net yield of two \(\text{ATP}\) from glycolysis is dwarfed by the approximately 32 \(\text{ATP}\) molecules generated by mitochondrial processes.