Oxidative+Phosphorylation

During oxidative phosphorylation, electrons are transferred from [|electron donors] to [|electron acceptors] such as [|oxygen], in [|redox reactions]. These redox reactions release energy, which is used to form ATP. In [|eukaryotes], these redox reactions are carried out by a series of [|protein complexes] within [|mitochondria] , whereas, in [|prokaryotes] , these proteins are located in the cells' inner membranes. These linked sets of proteins are called [|electron transport chains]. In eukaryotes, five main protein complexes are involved, whereas in prokaryotes many different enzymes are present, using a variety of electron donors and acceptors. The energy released by electrons flowing through this electron transport chain is used to transport protons across the [|inner mitochondrial membrane], in a process called// [|chemiosmosis] //. This generates [|potential energy] in the form of a [|pH] gradient and an [|electrical potential] across this membrane. This store of energy is tapped by allowing protons to flow back across the membrane and down this gradient, through a large [|enzyme] called [|ATP synthase]. This enzyme uses this energy to generate ATP from [|adenosine diphosphate] (ADP), in a [|phosphorylation] reaction. This reaction is driven by the proton flow, which forces the [|rotation] of a part of the enzyme; the ATP synthase is a rotary mechanical motor. Although oxidative phosphorylation is a vital part of [|metabolism], it produces [|reactive oxygen species] such as [|superoxide] and [|hydrogen peroxide] , which lead to propagation of [|free radicals] , damaging cells and contributing to [|disease] and, possibly, [|aging] ( [|senescence] ). The enzymes carrying out this metabolic pathway are also the target of many drugs and poisons that [|inhibit] their activities.
 * Oxidative phosphorylation** (or OXPHOS in short) is a [|metabolic pathway] that uses energy released by the [|oxidation] of [|nutrients] to produce [|adenosine triphosphate] (ATP). Although the many forms of life on earth use a range of different nutrients, almost all [|aerobic organisms] carry out oxidative phosphorylation to produce ATP, the molecule that supplies energy to [|metabolism] . This pathway is probably so pervasive because it is a highly efficient way of releasing energy, compared to alternative [|fermentation] processes such as anaerobic [|glycolysis].



The [|NADH] and [|FADH2] formed in glycolysis, fatty acid oxidation, and the citric acid cycle are energy-rich molecules because each contains a pair of electrons having a high transfer potential. When these electrons are used to reduce molecular oxygen to water, a large amount of free energy is liberated, which can be used to generate [|ATP]. //Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH// //2// //to O// //2// //by a series of electron carriers.// This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms ( [|Figure 18.1] ). For example, oxidative phosphorylation generates 26 of the 30 molecules of ATP that are formed when glucose is completely oxidized to CO 2 and H 2 O. Oxidative phosphorylation is conceptually simple and mechanistically complex. Indeed, the unraveling of the mechanism of oxidative phosphorylation has been one of the most challenging problems of biochemistry. The flow of electrons from [|NADH] or [|FADH2] to O 2 through protein complexes located in the mitochondrial inner membrane leads to the pumping of protons out of the mitochondrial matrix. The resulting uneven distribution of protons generates a pH gradient and a transmembrane electrical potential that creates a //proton-motive force//. [|ATP] is synthesized when protons flow back to the mitochondrial matrix through an enzyme complex. Thus, //the oxidation of fuels and the phosphorylation of [|ADP] are coupled by a proton gradient across the inner mitochondrial membrane// ( [|Figure 18.2] ). //Oxidative phosphorylation is the culmination of a series of energy transformations// that are called //cellular respiration// or simply//respiration// in their entirety. First, carbon fuels are oxidized in the citric acid cycle to yield electrons with high transfer potential. Then, this electron-motive force is converted into a proton-motive force and, finally, the proton-motive force is converted into phosphoryl transfer potential. The conversion of electron-motive force into proton-motive force is carried out by three electron-driven proton pumps— [|NADH] - [|Q] oxidoreductase, Q-cytochrome //c// oxidoreductase, and cytochrome //c// oxidase. These large transmembrane complexes contain multiple oxidation-reduction centers, including quinones, flavins, iron-sulfur clusters, hemes, and copper ions. The final phase of oxidative phosphorylation is carried out by // [|ATP] synthase,// an ATP-synthesizing assembly that is driven by the flow of protons back into the mitochondrial matrix. Components of this remarkable enzyme rotate as part of its catalytic mechanism. Oxidative phosphorylation vividly shows that //proton gradients are an interconvertible currency of free energy in biological systems.//