| ALT_DEFINITION
| - The body gets energy through the oxidation of food such as glucose and fatty acids. The chemical energy contained in these foods is extracted and converted until it reaches a common form, the high-energy phosphate bonds of ATP. The hydrolysis of ATP is highly favorable and is coupled to a variety of energetically unfavorable processes to drive them forward. Most of the energy of glucose or fatty acids is extracted through oxidation to produce the reduced high-energy electron carriers NADH and FADH2. From there, the energy is transferred next to the electron transport system associated with the mitochondrial inner membrane. This chain includes a series of protein complexes and non-membrane cofactors that transfer the electrons from NADH and FADH2 in a series of redox reactions from carrier to carrier. Oxygen is the final electron acceptor at the end of the chain, resulting in the production of water. The oxygen we breathe, and which is transported by hemoglobin in the blood to all of the tissues, serves this purpose and allows electron transport to occur. As the electrons pass through the chain, they transfer their energy to the complexes, which use the energy to pump protons out of the mitochondrial matrix, creating a proton gradient across the inner mitochondrial membrane. The chemical energy that started with glucose, and was transferred to NADH and FADH2, is then converted to the energy of a concentration gradient. The inner mitochondrial membrane is impermeable to protons on its own, so the energy of the proton gradient is stable, waiting to be recaptured. The energy is recaptured by ATP synthase in the inner mitochondrial membrane. This enzyme allows protons to flow back down their concentration gradient across the membrane, and in the process uses the energy of the gradient to drive ATP synthesis. The movement of the electrons through electron transport, the proton gradient and ATP synthesis are all coupled processes that require each other to occur. The cell does not store energy as ATP, but only has enough ATP on hand for its immediate energy needs. If electron transport ceases or is inhibited, then ATP synthesis also rapidly halts. This regulation ensures that ATP production closely matches the needs of the cell. Glycolysis and the Krebs cycle are also closely linked to the energy needs of the cell. The abundance of ATP, NADH and pathway intermediates regulates key steps in these pathways so that they are activated when energy is required to feed the electron transport system and they are inhibited when not needed to save metabolic energy. If oxygen is absent, electron transport and the Krebs cycle rapidly halt, leaving glycolysis and fermentation as the main means of energy production. During aerobic exercise, the rapid consumption of ATP leads to use of the proton gradient to make more ATP, increased electron transport to regenerate the proton gradient, increased oxygen consumption, and increased activity of the Krebs cycle and glycolysis to supply high energy electrons to drive electron transport. Uncoupling agents allow protons to flow across the mitochondrial membrane without producing ATP. The chemical compound dinitrophenol (DNP), for example, can transport protons across the inner mitochondrial membrane without ATP synthase. In the presence of dinitrophenol, energy is consumed to pump protons out of mitochondria, but this energy is not recaptured in chemical form in ATP. Instead, this energy is released as heat. Dinitrophenol was once used as diet remedy to lose weight without exercise or diet, but this compound is a metabolic poison and resulted in deaths in when purposefully given to humans. Proteins also can act as uncoupling agents in the mitochondria. A mitochondrial uncoupling protein is found in brown adipose tissue. An increase in the activity of uncoupling proteins increases heat production by allowing protons to flow down their gradient without making ATP and may serve as protection against cold, as well as a potential means of obesity control.BIOCARTA
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