In cell biology, respiration is defined as the process of liberating energy from fuel molecules then storing it in a more accessible form, namely the high-energy phosphate bonds of the molecule ATP (adenosine triphosphate). This process can occur anaerobically (without oxygen), as with many bacteria; however, in multicellular organisms, respiration is primarily aerobic (requiring oxygen). This article will explore respiration, with an emphasis on how the organelles called mitochondria actually work like tiny proton-powered batteries.
In chemistry fuel molecules, including sugars, proteins and fats, burn in the presence of oxygen to yield carbon dioxide, water and heat. Scientists term this process combustion. In living cells, the overall objective of respiration remains the same as combustion, i.e., to convert carbon containing compounds into CO2, water and energy. The main difference, of course, is that cells utilize a highly regulated series of enzymes and ion pumps to accomplish this task.
Cellular respiration consists of three stages: glycolysis (fermentation), the Krebs Cycle and the electron transport chain/oxidative phosphorylation. In glycolysis, sugars (usually glucose) are coverted to pyruvate in ten steps. During certain enzymatic steps of glycolysis, ADP is directly phosphorylated to form ATP as part of a coupled chemical reaction.
Many unicellular organisms, most notably bacteria, can produce enough ATP by anaerobic respiration alone to meet their energy needs. Multicellular organisms, however, must rely on a process called oxidative phosphorylation for the bulk of ATP production. As the name implies, oxidative phosphorylation requires the presence of oxygen to take place.
In aerobic respiration, the pyruvate generated in glycolysis enters an organelle called the mitochondrion. Here a protein complex called pyruvate dehydrogenase irreversibly turns pyruvate into carbon dioxide and a two-carbon compound called acetyl-CoA. Acetyl CoA then enters an oxygen-dependent series of reactions in the mitochondrial matrix called the Krebs Cycle.
The Krebs Cycle itself generates two ATP equivalents. The main energy yield from the Krebs Cycle occurs when Acetyl CoA is metabolized to carbon dioxide. These reactions generate high-energy electrons in the form of NADH and FADH2. These two energy carriers, derived from B vitamins, promptly deliver these electrons to a membrane-bound complex of iron containing proteins called cytochromes. The cytochromes and their cofactors comprise the electron transport chain, which shuttles the electrons like hot potatoes until they reach the final electron acceptor, molecular oxygen.
The electron transport chain somehow harnesses the energy of the electrons to pump protons into the intermembrane space between the inner and outer mitochondrial membranes. This creates an electrochemical gradient that the mitochondria use to drive ATP production. Until 1961, biologists did not know how the proton gradient was coupled to the synthesis of ATP. That year, Peter Mitchell proposed that the flow of protons through special protein complexes on the inner mitochondrial membrane provided the free energy necessary to convert ADP to ATP. Essentially, mitochondria act as tiny proton batteries, perpetually charged by the electron transport chain.
In the decades following Mitchell’s hypothesis, scientists have largely figured out how these ATP synthase complexes work. Although the exact mechanism is unclear, it seems that ATP synthase works as a rotor-driven pump powered by proton flow. As the diagram shows, a single proton causes the rotor segment to rotate 120 degrees. Each time three protons spin the rotor a full 360 degrees, the complex releases an ATP molecule.
The thermodynamic efficiency of aerobic respiration (the conversion of one glucose to 36 ATP molecules) is estimated to be around 38 percent. At first glance this may seem low, but keep in mind, most engines run at a far lower efficiency when they burn gasoline. In the case of cellular respiration, the energy lost as heat helps keep your body temperature at 98.6 degrees F.
Sometimes, it becomes necessary for the body to generate even more heat, for example during prolonged exposure to cold. In addition to muscle contractions, human bodies contain a specialized form of fat tissue surrounding certain arteries called brown adipose tissue. Like other cells, these fat cells break down fatty acids to generate a proton gradient, but this time the protons are not used to produce ATP.
Instead, the mitochondria within these adipocytes contain a special protein called thermogenin. Thermogenin (which literally means heat generator) short circuits the mitochondrial proton battery by allowing protons to reenter the mitochondrial matrix without passing through an ATP synthase complex. The end result is that fuel molecules are burned for heat rather than to generate ATP. Certain plants such as skunk cabbage also contain thermogenin. This allows them to warm their leaves, which in turn scatter more odorants to attract insects to pollinate the plant.