ATP synthesis by oxidative phosphorylation

Wall Piece IV (1985), a kinetic sculpture by George Rhoads. This complex meehanieal art form can be viewed as a metaphor for the molecular apparatus underlying electron transport and ATP synthesis by oxidative phosphorylation. (1985 ty George Rhoaeh)... 

Vance, J.E., eds.), pp. 116-142, Benjamin/Cummings Publishing Co., Menlo Park, California. Senior, A.E. (1988). ATP synthesis by oxidative phosphorylation. Physiological Rev. 68, 177-230. Senior, A.E. (1990). The proton-translocating ATPase of Esherichia colt. Ann. Rev. Biophys. Chem. 19,7- 1. 

Many enzymes in the mitochondria, including those of the citric acid cycle and pyruvate dehydrogenase, produce NADH, aU of which can be oxidized in the electron transport chain and in the process, capture energy for ATP synthesis by oxidative phosphorylation. If NADH is produced in the cytoplasm, either the malate shuttle or the a-glycerol phosphate shuttle can transfer the electrons into the mitochondria for delivery to the ETC. Once NADH has been oxidized, the NAD can again be used by enzymes that require it. 

The electron transport chain is present in the inner mitochondrial membrane and is the final common pathway by which electrons derived from different fuels of the body flow to oxygen. Electron transport and ATP synthesis by oxidative phosphorylation proceed continuously in all tissues that contain mitochondria. 

A) the mitochondrial proton pump slows down, preventing ATP synthesis by oxidative phosphorylation... 

How does brown fat generate heat and burn excess calories For the answer we must turn to the mitochondrion. In addition to the ATP synthase and the electron transport system proteins that are found in all mitochondria, there is a protein in the inner mitochondrial membrane of brown fat tissue called thermogenin. This protein has a channel in the center through which the protons (H ) of the intermembrane space could pass back into the mitochondrial matrix. Under normal conditions this channel is plugged by a GDP molecule so that it remains closed and the proton gradient can continue to drive ATP synthesis by oxidative phosphorylation. 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eukaryotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessary for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphorylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eukaryotes, the mitochondrion is the site of most energy-yielding... 

Binding Change Mechanism for ATP Synthesis by Oxidative Phosphorylation and Photophosphorylation Richard L. Cross, David Cunmngjwm, and James K. Tamura... 

Glycolysis and the citric acid cycle (to be discussed in Chapter 20) are coupled via phosphofructokinase, because citrate, an intermediate in the citric acid cycle, is an allosteric inhibitor of phosphofructokinase. When the citric acid cycle reaches saturation, glycolysis (which feeds the citric acid cycle under aerobic conditions) slows down. The citric acid cycle directs electrons into the electron transport chain (for the purpose of ATP synthesis in oxidative phosphorylation) and also provides precursor molecules for biosynthetic pathways. Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated. 

Phenolic compounds naturally occurring in plants have induced many physiological responses that duplicate those reported for ozone and/or peroxyacetylnitrate (PAN). Chlorogenic acid is a competitive inhibitor of lAA-oxidase (35) and plant growth is adversely affected by increased concentrations of auxins (36). Concentrations of chlorogenic acid are increased in tobacco tissue exposed to ozone ( ) Phenols inhibit ATP synthesis (37), oxidative phosphorylation ( ) and SH enzyme activity (27) they increase respiration (38), reduce CO2 fixation (22), modify both membrane permeability (40) and oxidation rate of reduced NADH... 

The overabundance of NADH also inhibits fatty acid oxidation. The metabolic purpose of fatty acid oxidation Is to generate NADH for ATP generation by oxidative phosphorylation, but an alcohol consumer s NADH needs are met by ethanol metabolism. In fact, the excess NADH signals that conditions are right for fatty acid synthesis. Hence, triacylglyc-erols accumulate in the liver, leading to a condition known as Tatty liver."... 

The acetyl-CoA molecules produced by fatty acid oxidation are converted via the citric acid cycle to C02 and H20 as additional NADH and FADH2 are formed. A portion of the energy released as NADH and FADH2 are oxidized by the ETC is later captured in ATP synthesis via oxidative phosphorylation. The complete oxidation of acetyl-CoA is discussed in Chapter 10. The calculation of total number of ATP that can be generated from palmitoyl is reviewed next. 

In addition to powering ATP synthesis, the proton-motive force across the inner mitochondrial membrane also powers the exchange of ATP formed by oxidative phosphorylation inside the mitochondrion for ADP and Pj in the cytosol. This exchange, which is required for oxidative phosphorylation to continue, is mediated by two proteins in the inner membrane a phosphate transporter (HP04 /OH antiporter) and an ATP/ADP antiporter (Figure 8-28). 

The thylakoid lumen is the part of the chloroplast enclosed by the thylakoid membrane (Figure 17.15). During photosynthesis, electrons are pumped into the thylakoid lumen from the stroma, forming a proton gradient. Movement of the protons out of the thylakoid lumen through the CFO-CFl complex back to the stroma provides the driving force for photophosphorylation, the process of making ATP in photosynthesis. A similar mechanism is responsible for ATP synthesis in oxidative phosphorylation. 

The electrochemical gradient couples the rate of the electron transport chain to the rate of ATP synthesis. Because electron flow requires proton pumping, electron flow cannot occur faster than protons are used for ATP synthesis (coupled oxidative phosphorylation) or returned to the matrix by a mechanism that short circuits the ATP synthase pore (uncoupling). 

After 10 h, the second phase was characterised by a gradual increase in heat flow rate that was restored to its former value by 13 h (see Figure 35A) This was entirely due to anaerobic processes (Figure 35B). The carbon flux was found to be double the level in phase 1. This was presumably due to the much lower yield of ATP by such processes that would be dominated by the reduction of pyruvate to lactate in substrate phosphorylation, with the net synthesis of 2 mol ATP per mol Glc The increased glycolytic flux would result in a decreased pH as seen in Figure 35A. It was not possible of course to monitor the viability of the cells over the 20-h period but one would imagine that the accumulation of toxic lactate [53] would have a profound effect on the cells. Indirectly, this may be supposed from the fact that the heat flow rate during this phase was approximately at the same level as in phase 1, despite the fact that I5x more carbon is required to produce the same quantity of ATP as by oxidative phosphorylation. For the purpose of this speculation, the reliable number calculated by Beavis [62] for the stoichiometric yield of ATP per glc of 33 has been chosen, but there are many other values to be found in the literature (see Section 3.2.8). 

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

Under these conditions, what is the maximum ratio of [ATP]/[ADP] attainable by oxidative phosphorylation when [PJ = 1 mM (Assume AG° for ATP synthesis = +30.5 kj/mol.)... 

The individual steps of the multistep chemical reduction of COj with the aid of NADPHj require an energy supply. This supply is secured by participation of ATP molecules in these steps. The chloroplasts of plants contain few mitochondria. Hence, the ATP molecules are formed in plants not by oxidative phosphorylation of ADP but by a phosphorylation reaction coupled with the individual steps of the photosynthesis reaction, particularly with the steps in the transition from PSII to PSI. The mechanism of ATP synthesis evidently is similar to the electrochemical mechanism involved in their formation by oxidative phosphorylation owing to concentration gradients of the hydrogen ions between the two sides of internal chloroplast membranes, a certain membrane potential develops on account of which the ATP can be synthesized from ADP. Three molecules of ATP are involved in the reaction per molecule of COj. 

How Many Protons in a Mitochondrion Electron transfer translocates protons from the mitochondrial matrix to the external medium, establishing a pH gradient across the inner membrane (outside more acidic than inside). The tendency of protons to diffuse back into the matrix is the driving force for ATP synthesis by ATP synthase. During oxidative phosphorylation by a suspension of mitochondria in a medium of pH 7.4, the pH of the matrix has been measured as 7.7. 

Chemolithotrophic organisms often grow slowly, making study of their metabolism difficult.310 Nevertheless, these bacteria usually use electron transport chains similar to those of mitochondria. ATP is formed by oxidative phosphorylation, the amount formed per electron pair depending upon the number of proton-pumping sites in the chain. This, in turn, depends upon the electrode potentials of the reactions involved. For example, H2, when oxidized by 02, leads to passage of electrons through the entire electron transport chain with synthesis of 3 molecules of ATP per electron pair. On the other hand, oxidation by 02 of nitrite, for which E° (pH 7) = +0.42 V, can make use only of the site III part of the chain. Not only is the yield of ATP less than in the oxidation of H2 but also there is another problem. Whereas reduced pyridine... 

Nitrate respiration can support the synthesis of ATP, while proton pumping has been quantified for several physiological substrates. Stoichiometries of about 4H+/NO, and 2H+/N03" have been found for L-malate and formate, and succinate, D-lactate and glycerol respectively. There is evidence that about one mole of ATP is synthesized by oxidative phosphorylation per mole of nitrate reduced.1440... 

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