ATP synthase location

These protons can pass back into the cytoplasm via ATP synthases located in the same membrane with their catalytic centers in the cytosol (see Figs. 18-5 and 18-14). 

Oxidative phosphorylation is ATP synthesis linked to the oxidation of NADH and FADH2 by electron transport through the respiratory chain. This occurs via a mechanism originally proposed as the chemiosmotic hypothesis. Energy liberated by electron transport is used to pump H+ ions out of the mitochondrion to create an electrochemical proton (H+) gradient. The protons flow back into the mitochondrion through the ATP synthase located in the inner mitochondrial membrane, and this drives ATP synthesis. Approximately three ATP molecules are synthesized per NADH oxidized and approximately two ATPs are synthesized per FADH2 oxidized. 

Oxidative phosphorylation is the name given to the synthesis of ATP (phosphorylation) that occurs when NADH and FADH2 are oxidized (hence oxidative) by electron transport through the respiratory chain. Unlike substrate level phosphorylation (see Topics J3 and LI), it does not involve phosphorylated chemical intermediates. Rather, a very different mechanism was proposed by Peter Mitchell in 1961, the chemiosmotic hypothesis. This proposes that energy liberated by electron transport is used to create a proton gradient across the mitochondrial inner membrane and that it is this that is used to drive ATP synthesis. Thus the proton gradient couples electron transport and ATP synthesis, not a chemical intermediate. The evidence is overwhelming that this is indeed the way that oxidative phosphorylation works. The actual synthesis of ATP is carried out by an enzyme called ATP synthase located in the inner mitochondrial membrane (Fig. 3). 

The proton gradient drives ATP synthesis via an ATP synthase located in the thylakoid membrane (photophosphorylation). Since the electron transport involves a linear array of electron carriers, the system is called noncyclic photophosphorylation. 

ATP is produced from ADP and phosphate by an enzyme, ATP synthase, located in the inner mitochondrian or chloroplast membrane. The energy is delivered from a current of H+ ions into the mitochondrian matrix. Some important pesticides inhibit this enzyme, leading to a halt in ATP production. 

A Membrane-Located ATP Synthase Functions as a Rotary Motor to Form ATP... 

The electrochemical potential difference is used to drive a membrane-located ATP synthase which in the presence of P + ADP forms ATP (Figure 12-8). Scattered over the surface of the inner membrane are the phos-phorylating complexes, ATP synthase, responsible for the production of ATP (Figure 12-1). These consist of several protein subunits, collectively known as F, which project into the matrix and which contain the phosphorylation mechanism (Figure 12-8). These sub-... 

Electron microscopy of sectioned chloroplasts shows ATP synthase complexes as knoblike projections on the outside (stromal or N) surface of thylalcoid membranes these complexes correspond to the ATP synthase complexes seen to project on the inside (matrix or N) surface of the inner mitochondrial membrane. Thus the relationship between the orientation of the ATP synthase and the direction of proton pumping is the same in chloroplasts and mitochondria. In both cases, the Fl portion of ATP synthase is located on the more alkaline (N) side of the membrane through which protons flow down their concentration gradient the direction of proton flow relative to Fi is the same in both cases P to N (Fig. 19-58). 

These complexes are usually named as follows I, NADH-ubiquinone oxidoreductase II, succinate-ubiquinone oxidoreductase III, ubiquinol-cytochrome c oxidoreductase IV, cytochrome c oxidase. The designation complex V is sometimes applied to ATP synthase (Fig. 18-14). Chemical analysis of the electron transport complexes verified the probable location of some components in the intact chain. For example, a high iron content was found in both complexes I and II and copper in complex IV. 

ATP synthase, whose knobs also protrude into the stroma. A photosynthetic unit can also be defined chemically by the number of various types of molecules present in a chloroplast membrane for each four manganese atoms (Table 23-2). Separate units contain PSI and PSII. These reaction centers appear to have a different distribution within the thylakoids, the PSI units being located principally in the unstacked membranes and the PSII units in the grana stacks.255 259... 

In many laboratories attempts were made to discover a high-energy intermediate consisting of a respiratory enzyme or coenzyme and ATP-synthase component. Though this intermediate is located at the central place in the chemical scheme, nobody succeeded in either observing or extracting a compound of this type. 

According to the concept discussed in Refs [24, 25], the F0 factor is responsible for H+ translocation between the environment (in relation to mitochondrion), aqueous phase and the membrane, where fixed proton-acceptor groups X are located. If H+/ATP stoichiometry equals 2, they may be absorbed in the ATP-synthase reaction ... 

ATP synthase is located in the inner mitochondrial membrane. It consists of two major components, F, ATPase [seen as spheres under the electron microscope and with a subunit structure of (aP ySe] attached to component F0 (coupling factor 0) which is a proton channel spanning this membrane. Hence, ATP synthase is also known as F0F, ATPase. In mitochondria, this complete complex uses the energy released by electron transport to drive ATP synthesis but, in isolation, F ATPase hydrolyzes ATP. During ATP hydrolysis, and presumably also during ATP synthesis, subunit y of F, ATPase rotates relative to (aP)3 and is the smallest rotatory engine known in nature. 

The developed H+ concentration gradient plus an electric potential across the membrane supply the driving force for ATP synthesis from ADP and Pi, a thermodynamically unfavorable reaction catalyzed by ATP synthase (Karrasch and Walker, 1999). The latter is a mitochondrial enzyme located on, and spanning, the inner mitochondrial membrane. At least when in submitochondrial particles, ATP synthase saturation kinetics involve ADP positive site-site interactions in catalysis. One group has proposed that ADP saturation in vivo also shows site-site interactions ( , the interaction or Hill coefficient increasing from 1, meaning no interaction, to 2) however, others have not found this, so this issue at this time must be considered to remain unresolved. 

This pathway, also located in the mitochondria, generates acetylCoA which is then completely metabolized by the Krebs cycle, the ETS, and ATP synthase. The overall equation for fatty acid oxidation, using palmitate as an example, can be written as ... 

Approximately 1000 proteins comprise the mitochondrion the majority are encoded on genes located on nuclear DNA. In fact, as seen in Figure 8-5, the mtDNA encodes only 13 proteins. These mtDNA-encoded proteins are the seven subunits (ND1,2,3,4,4L, 5, and 6) of the NADH-dehydrogenase (RC I) one subunit (cytochrome b) of RC III three subunits (CO I, II, and III) of cytochrome c oxidase (RC IV) and two subunits (A6 and A8) of the ATP synthase (RC V).A11 of these proteins are components of the ETC or the ATP synthase involved in OXPHOS. In addition to these 13 proteincoding genes, the mtDNA encodes 22 mitochondrial transfer ribonucleic acids (tRNAs) and two ribosomal RNA (rRNA) molecules (the large 16S rRNA and the small 12S rRNA). 

The genes for the y and 8 subunits of CFj and for CFq subunit II are most likely located in nuclear DNA, but they have not yet been isolated. Each of these polypeptides has been shown to be synthesized as a larger precursor form on translation of poly(A) RNA in vitro [142,146]. The isolation and characterization of the nuclear genes for these three subunits of ATP synthase is urgently required. 

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