Cellular respiration is the set of biochemical processes by which cells extract usable energy from organic molecules and convert much of that energy into ATP, the principal immediately usable energy currency of cells. In many organisms, glucose is an important starting substrate, although cells can also obtain energy from fatty acids, amino acids and other compounds.
Aerobic cellular respiration uses oxygen as the final electron acceptor in the electron transport chain and can extract a large amount of energy from reduced carbon compounds. In eukaryotic cells, major stages occur in different cellular compartments. Glycolysis takes place in the cytosol, while the citric acid cycle and oxidative phosphorylation occur primarily in mitochondria. The overall process involves controlled oxidation of fuel molecules rather than a single reaction. Energy is released through many enzyme mediated steps, allowing cells to capture a substantial proportion of it in ATP and other energy carrying molecules rather than releasing all of it as heat at once.
Glycolysis is the first major stage of glucose breakdown and occurs in the cytosol. A six carbon glucose molecule is converted through a sequence of reactions into two three carbon molecules of pyruvate. The pathway requires an initial investment of ATP but subsequently generates more ATP and produces reduced electron carriers in the form of NADH.
The net direct ATP yield from glycolysis is two ATP molecules per glucose molecule, although the exact accounting can depend on cellular conditions and the transport mechanisms involved in later stages. Glycolysis does not directly require oxygen, so it can occur under anaerobic conditions as well as aerobic ones. Its products can therefore enter different metabolic pathways depending on the organism and environmental conditions. In aerobic cells, pyruvate is normally transported into mitochondria and converted into acetyl coenzyme A before entering the citric acid cycle. Glycolysis is evolutionarily widespread and is a central metabolic pathway in organisms ranging from bacteria to humans.
The citric acid cycle, also called the Krebs cycle or tricarboxylic acid cycle, oxidises acetyl groups and transfers high energy electrons to carrier molecules. In eukaryotic cells, the cycle takes place mainly in the mitochondrial matrix. Acetyl coenzyme A enters the cycle and combines with oxaloacetate to form citrate, which is then processed through a sequence of reactions that regenerate oxaloacetate.
Per turn of the cycle, carbon atoms derived from the acetyl group are ultimately released as carbon dioxide, while NADH and FADH2 are produced. A small amount of ATP or an equivalent nucleotide triphosphate is also generated directly. Because one glucose molecule produces two pyruvate molecules and therefore two acetyl coenzyme A molecules, the cycle operates twice per glucose. The main importance of the cycle is not its small direct ATP production but its generation of reduced electron carriers that deliver electrons to the respiratory chain.
Oxidative phosphorylation is the stage that generates most ATP during aerobic respiration. Electrons from NADH and FADH2 are transferred through a series of protein complexes embedded in the inner mitochondrial membrane in eukaryotes. As electrons move through the electron transport chain, energy is used to pump protons from the mitochondrial matrix into the intermembrane space. This establishes an electrochemical proton gradient across the inner membrane.
Protons then flow back through ATP synthase, a molecular enzyme complex that uses the energy of this movement to drive ATP formation from ADP and inorganic phosphate. Oxygen serves as the terminal electron acceptor and combines with electrons and protons to form water. The coupling between electron transport, proton movement and ATP synthesis is called chemiosmosis. This mechanism converts energy stored in reduced electron carriers into a form that cells can directly use for many biochemical processes.
Cellular respiration is an oxidation reduction process. Glucose and other fuel molecules are progressively oxidised, meaning that their carbon and hydrogen atoms participate in reactions that transfer electrons to carriers such as NAD plus and FAD. These carriers become reduced to NADH and FADH2 and subsequently deliver electrons to the respiratory chain. Oxygen is reduced to water at the end of aerobic electron transport.
The overall transformation is energetically favourable because electrons move from relatively high energy donors to a strong terminal electron acceptor. The controlled nature of respiration allows energy to be captured efficiently. The complete oxidation of one glucose molecule can be represented approximately by the equation C6H12O6 plus 6 O2 produces 6 CO2 plus 6 H2O, although the biochemical process consists of many individual reactions. ATP yield varies with organism, cellular conditions and assumptions about transport costs, but aerobic respiration commonly produces roughly 30 to 32 ATP per glucose in modern textbook accounting for many mammalian cells.
Not all cellular respiration is aerobic. Anaerobic organisms can use alternative terminal electron acceptors such as nitrate, sulphate or carbon dioxide, depending on their metabolic capabilities. Fermentation is different from anaerobic respiration because fermentation does not use an external terminal electron acceptor through an electron transport chain. Instead, an organic molecule derived from the original nutrient accepts electrons so that NAD plus can be regenerated.
In human muscle cells under conditions where oxygen delivery cannot meet demand, pyruvate can be reduced to lactate, allowing glycolysis to continue temporarily. Yeast can convert pyruvate to ethanol and carbon dioxide during alcoholic fermentation. These pathways produce far less ATP per glucose than complete aerobic oxidation, but they can support ATP production when respiratory-chain operation is unavailable or when particular environmental conditions favour alternative metabolism.
Cellular respiration supports almost every major energy demanding function of living cells. ATP generated by respiration powers active transport across membranes, biosynthetic reactions, movement of molecular motors, maintenance of ion gradients, signalling processes and many forms of cellular work. Respiration is closely linked to other metabolic pathways because its intermediates can be diverted into synthesis of amino acids, lipids, nucleotides and other molecules. Conversely, fats and proteins can enter respiratory pathways at different points and contribute to ATP production.
Mitochondria are therefore not simply energy factories but central metabolic organelles involved in broader cellular regulation. Respiration also produces heat, which can contribute to temperature regulation in some animals. Reactive oxygen species can arise as byproducts of electron transfer, and cells possess antioxidant systems that control their levels. Thus respiration provides energy while simultaneously influencing redox balance, biosynthesis and cellular signalling.
The importance of cellular respiration extends from individual cells to ecosystems and the global carbon cycle. Animals obtain chemical energy by consuming organic molecules, plants use respiration to release energy from compounds they have produced by photosynthesis, and microorganisms perform diverse respiratory processes that drive nutrient cycles.
Photosynthesis and aerobic respiration are strongly interconnected: photosynthesis uses carbon dioxide and water to store energy in organic molecules, while aerobic respiration uses those molecules and oxygen to release usable chemical energy while producing carbon dioxide and water. Respiration is therefore not simply the reverse of photosynthesis because the two processes use different pathways and occur under different regulatory conditions. Cellular respiration is better understood as a coordinated network of energy transforming reactions whose details vary among organisms. Its central biological function is to make energy from chemical nutrients available in controlled forms that can support growth, maintenance, reproduction, movement and all other energy dependent cellular activities.
