Instruct: Given a question, retrieve passages that can help answer the question.
Query: Is oxidative phosphorylation new?
The field of oxidative phosphorylation began with the report in 1906 by Arthur Harden of a vital role for phosphate in cellular fermentation, but initially only sugar phosphates were known to be involved.[94] However, in the early 1940s, the link between the oxidation of sugars and the generation of ATP was firmly established by Herman Kalckar,[95] confirming the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941.[96] Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NADH linked metabolic pathways such as the citric acid cycle and the synthesis of ATP.[97] The term oxidative phosphorylation was coined by Volodymyr Belitser in 1939.[98][99]
The composition of the matrix based on its structures and contents produce an environment that allows the anabolic and catabolic pathways to proceed favorably for. The electron transport chain and enzymes in the matrix play a large role in the citric acid cycle and oxidative phosphorylation. The citric acid cycle produces NADH and FADH2 through oxidation that will be reduced in oxidative phosphorylation to produce ATP.
Kalckar was fortunate to be working at an important period in biochemistry's evolution. The biochemical community was in the process of demonstrating the chemical reactions involved in breakdown of foodstuffs essential for growth. At the same time, physiologists were demonstrating the involvement of some of these reactions various physiological processes, e.g. muscle contraction. Kalckar's breakthrough work was the demonstration that organic compounds, which were phosphorylated during metabolic processes, involved oxygen consumption; oxygen consumption was linked to organic compound phosphorylation. His key experiment demonstrated that in frog muscles where glycolysis had been inhibited with iodoacetate, muscular contraction continued for a short period using phosphocreatine as a source of energy. Kalckar referred to this process as “aerobic phosphorylation” (now called oxidative phosphorylation, a biochemical process fundamental to all living organisms). The work was the first demonstration that carbohydrate oxidation and carbohydrate phosphorylation were linked, i.e. the two pathways were directly “coupled.” Furthermore, the study helped establish the basic phenomenon of oxidative phosphorylation, opened the way for its systematic exploration, and suggested for the first time that phosphate compounds acted as a link between catabolism and anabolism.
One of the effects of exercise is an increase in fatty acid metabolism, which provides more energy for the cell. One of the key pathways in AMPK’s regulation of fatty acid oxidation is the phosphorylation and inactivation of acetyl-CoA carboxylase. Acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 (CPT-1). CPT-1 transports fatty acids into the mitochondria for oxidation. Inactivation of ACC, therefore, results in increased fatty acid transport and subsequent oxidation. It is also thought that the decrease in malonyl-CoA occurs as a result of malonyl-CoA decarboxylase (MCD), which may be regulated by AMPK. MCD is an antagonist to ACC, decarboxylating malonyl-CoA to acetyl-CoA, resulting in decreased malonyl-CoA and increased CPT-1 and fatty acid oxidation.
AMPK also plays an important role in lipid metabolism in the liver. It has long been known that hepatic ACC has been regulated in the liver by phosphorylation. AMPK also phosphorylates and inactivates 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol synthesis. HMGR converts 3-hydroxy-3-methylglutaryl-CoA, which is made from acetyl-CoA, into mevalonic acid, which then travels down several more metabolic steps to become cholesterol. AMPK, therefore, helps regulate fatty acid oxidation and cholesterol synthesis.
Two carbon atoms are oxidized to CO, the energy from these reactions is transferred to other metabolic processes through GTP (or ATP), and as electrons in NADH and QH. The NADH generated in the citric acid cycle may later be oxidized (donate its electrons) to drive ATP synthesis in a type of process called oxidative phosphorylation. FADH is covalently attached to succinate dehydrogenase, an enzyme which functions both in the CAC and the mitochondrial electron transport chain in oxidative phosphorylation. FADH, therefore, facilitates transfer of electrons to coenzyme Q, which is the final electron acceptor of the reaction catalyzed by the succinate:ubiquinone oxidoreductase complex, also acting as an intermediate in the electron transport chain.
In contrast to the general similarity in structure and function of the electron transport chains in eukaryotes, bacteria and archaea possess a large variety of electron-transfer enzymes. These use an equally wide set of chemicals as substrates.[56] In common with eukaryotes, prokaryotic electron transport uses the energy released from the oxidation of a substrate to pump ions across a membrane and generate an electrochemical gradient. In the bacteria, oxidative phosphorylation in Escherichia coli is understood in most detail, while archaeal systems are at present poorly understood.[57]
In the 1960s, ATP was known to be the energy currency of life, but the mechanism by which ATP was created in the mitochondria was assumed to be by substrate-level phosphorylation. Mitchell's chemiosmotic hypothesis was the basis for understanding the actual process of oxidative phosphorylation. At the time, the biochemical mechanism of ATP synthesis by oxidative phosphorylation was unknown.
In eukaryotes, the enzymes in this electron transport system use the energy released from the oxidation of NADH to pump protons across the inner membrane of the mitochondrion. This causes protons to build up in the intermembrane space, and generates an electrochemical gradient across the membrane. The energy stored in this potential is then used by ATP synthase to produce ATP. Oxidative phosphorylation in the eukaryotic mitochondrion is the best-understood example of this process. The mitochondrion is present in almost all eukaryotes, with the exception of anaerobic protozoa such as Trichomonas vaginalis that instead reduce protons to hydrogen in a remnant mitochondrion called a hydrogenosome.[15]
Not all inhibitors of oxidative phosphorylation are toxins. In brown adipose tissue, regulated proton channels called uncoupling proteins can uncouple respiration from ATP synthesis.[92] This rapid respiration produces heat, and is particularly important as a way of maintaining body temperature for hibernating animals, although these proteins may also have a more general function in cells' responses to stress.[93]
There are several well-known drugs and toxins that inhibit oxidative phosphorylation. Although any one of these toxins inhibits only one enzyme in the electron transport chain, inhibition of any step in this process will halt the rest of the process. For example, if oligomycin inhibits ATP synthase, protons cannot pass back into the mitochondrion.[87] As a result, the proton pumps are unable to operate, as the gradient becomes too strong for them to overcome. NADH is then no longer oxidized and the citric acid cycle ceases to operate because the concentration of NAD+ falls below the concentration that these enzymes can use.
Oxidative phosphorylation (UK /ɒkˈsɪd.ə.tɪv/, US /ˈɑːk.sɪˌdeɪ.tɪv/)[1] is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing energy which is used to produce adenosine triphosphate (ATP). In most eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. 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.
Oligomycin A is an inhibitor of ATP synthase. In oxidative phosphorylation research, it is used to prevent state 3 (phosphorylating) respiration. Oligomycin A inhibits ATP synthase by blocking its proton channel (Fo subunit), which is necessary for oxidative phosphorylation of ADP to ATP (energy production). The inhibition of ATP synthesis by oligomycin A will significantly reduce electron flow through the electron transport chain; however, electron flow is not stopped completely due to a process known as "proton leak" or "mitochondrial uncoupling". This process is due to facilitated diffusion of protons into the mitochondrial matrix through an uncoupling protein such as thermogenin, or UCP1.
In some eukaryotes, such as the parasitic worm Ascaris suum, an enzyme similar to complex II, fumarate reductase (menaquinol:fumarate oxidoreductase, or QFR), operates in reverse to oxidize ubiquinol and reduce fumarate. This allows the worm to survive in the anaerobic environment of the large intestine, carrying out anaerobic oxidative phosphorylation with fumarate as the electron acceptor.[27] Another unconventional function of complex II is seen in the malaria parasite Plasmodium falciparum. Here, the reversed action of complex II as an oxidase is important in regenerating ubiquinol, which the parasite uses in an unusual form of pyrimidine biosynthesis.[28]
Chemiosmotic phosphorylation is the third pathway that produces ATP from inorganic phosphate and an ADP molecule. This process is part of oxidative phosphorylation.
The anhydride phosphoryl difluoride oxide (POF) reacts with oxides such as UO to yield difuorophosphates. Phosphoryl difluoride oxide also reacts with alkali fluorides to yield difluorophosphates.
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 produces 26 of the 30 equivalents of ATP generated in cellular respiration by transferring electrons from NADH or FADH2 to O2 through electron carriers. The energy released when electrons are passed from higher-energy NADH or FADH2 to the lower-energy O2 is required to phosphorylate ADP and once again generate ATP. It is this energy coupling and phosphorylation of ADP to ATP that gives the electron transport chain the name oxidative phosphorylation. 
By controlling the amount of available reducing equivalents generated by the Krebs cycle, Oxoglutarate dehydrogenase has a downstream regulatory effect on oxidative phosphorylation and ATP production. Reducing equivalents (such as NAD+/NADH) supply the electrons that run through the electron transport chain of oxidative phosphorylation. Increased Oxoglutarate dehydrogenase activation levels serve to increase the concentrations of NADH relative to NAD+. High NADH concentrations stimulate an increase in flux through oxidative phosphorylation.
In eukaryotes, oxidative phosphorylation occurs in the mitochondrial cristae. It comprises the electron transport chain that establishes a proton gradient (chemiosmotic potential) across the boundary of inner membrane by oxidizing the NADH produced from the Krebs cycle. ATP is synthesized by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP. The electrons are finally transferred to exogenous oxygen and, with the addition of two protons, water is formed.
It was subsequently deduced that PLS3 is an effector for the redistribution of cardiolipin from the inner to outer mitochondrial membrane. Thus, when PLS3 flips cardiolipin across the inner to outer membrane of the mitochondria, the oxidative phosphorylation induced is greatly disturbed. It was deduced experimentally that a lack of proper oxidative phosphorylation is directly linked with mitochondrial apoptosis. Thus, this PLS3-induced redistribution of cardiolipin during apoptosis has major effects on mitochondrial function.
The encoded protein (PHC) catalyzes the transport of phosphate from the cytosol into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. In the final steps of oxidative phosphorylation, this protein catalyzes the uptake of a phosphate ion with a proton across the mitochondrial inner membrane. The availability of inorganic phosphate for oxidative phosphorylation is mainly dependent on PHC activity. To substantially affect oxidative phosphorylation, PHC depletion must be severe, exceeding 85%. This protein may be involved in regulation of the mitochondrial permeability transition pore (mPTP). 
Sulfide oxidation can proceed under aerobic or anaerobic conditions. Aerobic sulfide-oxidizing bacteria usually oxidize sulfide to sulfate and are obligate or facultative chemolithoautotrophs. The latter can grow as heterotrophs, obtaining carbon from organic sources, or as autotrophs, using sulfide as the electron donor (energy source) for CO fixation. The oxidation of sulfide can proceed aerobically by two different mechanisms: substrate-level phosphorylation, which is dependent on adenosine monophosphate (AMP), and oxidative phosphorylation independent of AMP, which has been detected in several "Thiobacilli" ("T. denitrificans", "T. thioparus, T. novellus" and "T. neapolitanus"), as well as in "Acidithiobacillus ferrooxidans". The archaeon "Acidianus ambivalens" appears to possess both an ADP-dependent and an ADP independent pathway for the oxidation of sulfide. Similarly, both mechanisms operate in the chemoautotroph "Thiobacillus denitrificans", which can oxidize sulfide to sulfate anaerobically using nitrate as terminal electron acceptor which is in turn reduced to dinitrogen (N). Two other anaerobic strains that can perform a similar process were identified as similar to "Thiomicrospira denitrificans" and "Arcobacter".
The main difference between eukaryotic and prokaryotic oxidative phosphorylation is that bacteria and archaea use many different substances to donate or accept electrons. This allows prokaryotes to grow under a wide variety of environmental conditions.[58] In E. coli, for example, oxidative phosphorylation can be driven by a large number of pairs of reducing agents and oxidizing agents, which are listed below. The midpoint potential of a chemical measures how much energy is released when it is oxidized or reduced, with reducing agents having negative potentials and oxidizing agents positive potentials.
ATP, the "high-energy" exchange medium in the cell, is synthesized in the mitochondrion by addition of a third phosphate group to ADP in a process referred to as oxidative phosphorylation. ATP is also synthesized by substrate-level phosphorylation during glycolysis.
ATP is synthesized at the expense of solar energy by photophosphorylation in the chloroplasts of plant cells.
The table below describes the reactions involved when one glucose molecule is fully oxidized into carbon dioxide. It is assumed that all the reduced coenzymes are oxidized by the electron transport chain and used for oxidative phosphorylation.