All living cells require a constant supply of energy to function. The primary source of this fuel for your body is glucose, a simple sugar from the carbohydrates you eat. However, the energy in glucose isn’t in a form that cells can use directly and must be converted into a molecule called Adenosine Triphosphate, or ATP.
Think of ATP as the universal energy currency for the cell. Just as you can’t use a foreign currency at a local store, your cells cannot directly “spend” glucose; it must be exchanged into ATP. This molecule carries energy in its phosphate bonds, which can be broken to release energy that powers nearly every activity within the cell.
Glycolysis: The Initial Breakdown of Glucose
The journey of converting glucose into usable energy begins with glycolysis. This initial phase takes place in the cell’s cytoplasm and does not require oxygen. During glycolysis, a single six-carbon molecule of glucose is broken down through a sequence of ten enzyme-catalyzed reactions, a pathway found in nearly all living organisms.
The process starts by investing two ATP molecules to destabilize the glucose, preparing it to be split into two smaller, three-carbon molecules known as pyruvate. As the glucose is rearranged, the energy released is captured, resulting in a net production of two ATP molecules and two molecules of an electron carrier called NADH. While the energy yield is modest, glycolysis is a rapid way for cells to generate ATP.
The Krebs Cycle: Preparing for the Big Payoff
Following glycolysis, the two pyruvate molecules are transported into the mitochondria. Here, the next stage of energy extraction occurs: the Krebs Cycle, also known as the citric acid cycle. Before the cycle can begin, each pyruvate molecule is converted into a two-carbon compound called acetyl-CoA, releasing one molecule of carbon dioxide and generating another NADH molecule.
The acetyl-CoA then enters the Krebs Cycle, a series of eight reactions that dismantles it. The primary purpose of this cycle is not to produce a large quantity of ATP directly; only two ATP are generated per original glucose molecule. Instead, the main function is harvesting high-energy electrons. These are transferred to carrier molecules, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2).
These carriers act like rechargeable batteries, becoming “charged” with the high-energy electrons. For every glucose molecule that started this journey, the Krebs Cycle produces six NADH molecules and two FADH2 molecules. These loaded electron carriers hold the vast majority of the energy originally stored in the glucose molecule, and they transport this energy to the final stage of cellular respiration.
Oxidative Phosphorylation: The ATP Powerhouse
The final and most productive stage in energy conversion is oxidative phosphorylation, which takes place on the inner membrane of the mitochondria. Here, the energy carried by NADH and FADH2 from the Krebs cycle is used to generate a large amount of ATP. The process consists of two components, the electron transport chain and chemiosmosis, and it requires oxygen.
The electron transport chain is a series of protein complexes in the inner mitochondrial membrane. NADH and FADH2 molecules arrive and “drop off” their high-energy electrons to the first protein complex. As these electrons are passed from one protein to the next, they move to lower energy states. The energy released pumps protons across the inner membrane, creating a high concentration of protons in the space between the inner and outer membranes.
This accumulation of protons creates an electrochemical gradient, similar to water building up behind a dam. The only place for these protons to flow back into the matrix is through a protein channel called ATP synthase. As protons rush through this channel, they cause it to spin like a molecular turbine. This rotational energy drives the synthesis of ATP, producing approximately 32 to 34 ATP molecules per glucose molecule. At the end of the chain, the low-energy electrons are accepted by an oxygen molecule, which also picks up protons to form water.
Energy Production Without Oxygen
When oxygen is not available, the electron transport chain halts because there is no final electron acceptor, and the production of ATP via oxidative phosphorylation ceases. Cells must then rely on a less efficient method to produce energy known as anaerobic respiration. This process falls back on glycolysis as the sole source of ATP production.
To keep glycolysis running, the cell needs a steady supply of NAD+, the “uncharged” version of the electron carrier NADH. In aerobic conditions, NAD+ is regenerated during oxidative phosphorylation. Without oxygen, cells must use fermentation to regenerate NAD+ from the NADH produced during glycolysis. In human muscle cells during strenuous exercise, this involves converting pyruvate into lactic acid.
This conversion allows the cell to continue producing the two ATP molecules from glycolysis, providing a rapid but limited energy supply. The buildup of lactic acid is associated with the burning sensation in muscles during intense exertion. This anaerobic pathway is a short-term solution, but it is unsustainable as it extracts only a fraction of the energy available in glucose compared to the aerobic pathway.