Energy from oxidative phosphorylation

Two ATPs are used in glycolysis and four ATPs are synthesized for each molecule of glucose so that the net yield is two ATPs per glucose. Under aerobic conditions, the two NADH molecules arising from glycolysis also yield energy via oxidative phosphorylation. 

H.M. Kalckar. 1991. 50 years of biological research From oxidative phosphorylation to energy requiring transport regulationRev. Biochem. 60 1-37. (PubMed)... 

At the time I was in graduate school, it was recognized that living cells capture energy from oxidation of foodstuffs by making adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate. The ATP is then used in a myriad of functions — muscle contraction, nerve, brain, and kidney function, metabolic syntheses, and solute transport. How this oxidative phosphorylation occurrs remained for many years a major unsolved problem in biochemistry. 

DNP is a lipophilic molecule that binds reversibly with protons. It dissipates that proton gradient in mitochondria by transferring protons across the inner membrane. The uncoupling of electron transport from oxidative phosphorylation causes the energy from food to be dissipated as heat. DNP causes liver failure because of insufficient ATP synthesis in a metabolically demanding organ. 

Under ordinary circumstances in mammalian brain, the extracellular Na" " and K" " concentrations are 145 and 3 mM, respectively the intracellular concentrations 12 and 155 mM. However, because the resting membrane potential is a composite of a variety of factors (see earlier section), neither the Na nor the K" " gradient is at equilibrium with the electrical potential spanning the membrane. Hence, even at rest there is a small inward drift of Na+ and a small outward drift of. The Na + -K+ ATPase pump therefo -e maintains this gradient by utilizing energy derived from oxidative phosphorylation of the neuron. 

See also ATP as Free Energy Currency, Oxidative Phosphorylation (from Chapter 18)... 

Energy Yields from Oxidative Phosphorylation (Reactions)... 

In the TCA cycle, the 2-carbon acetyl group of acetyl CoA is oxidized to 2 CO2 molecules (see Fig. 20.1). The function of the cycle is to consawe the energy from this oxidation, which it accomplishes principally by transferring electrons from intermediates of the cycle to NAD and FAD. The eight electrons donated by the acetyl group eventually end up in three molecules of NADH and one of FAD(2H) (Fig. 20.2). As a consequence, ATP can be generated from oxidative phosphorylation when NADH and FAD(2H) donate these electrons to O2 via the electron transport chain. 

Otto Shape had difficulty losing weight because human fuel utilization is too efficient. His adipose tissue fatty acids are being converted to acetyl CoA, which is being oxidized in the TCA cycle, thereby generating NADH and FAD(2H). The energy in these compounds is used for ATP synthesis from oxidative phosphorylation. If his fuel utilization were less efficient and his ATP yield were lower, he would have to oxidize much greater amounts of fat to get the ATP he needs for exercise. 

Energy from fuel oxidation is converted to the high-energy phosphate bonds of adenosine triphosphate (ATP) by the process of oxidative phosphorylation. Most of the energy from oxidation of fuels in the TCA cycle and other pathways is conserved in the form of the reduced electron-accepting coenzymes, NADH and FAD(2H). The electron transport chain oxidizes NADH and FAD(2H), and donates the electrons to O2, which is reduced to H2O (Fig. 21.1). Energy from reduction 0/O2 is used for phosphorylation of adenosine diphosphate (ADP) to ATP by ATP synthase (FgFjATPase). The net yield of oxidative phosphorylation is approximately 2.5 moles of ATP per mole of NADH oxidized, or 1.5 moles of ATP per mole of FAD(2H) oxidized. 

The oxidation of fatty acids to acetyl CoA in the p-oxidation spiral conserves energy as FAD(2H) and NADH. FAD(2H) and NADH are oxidized in the electron transport chain, generating ATP from oxidative phosphorylation. Acetyl CoA is oxidized in the TCA cycle or converted to ketone bodies. 

The organism utilizes this energy in part as heat—to maintain its body temperature—and partly as chemical energy in the form of ATP gained from oxidative phosphorylation. The net result is ... 

Several possibilities exist to explain or rationalize the cessation of growth after a doubling in mass. However, the most likely seem to be either a loss of efficiency of energy production from oxidative phosphorylation due to the decrease in the lipid contents of the membrane, or perhaps most likely, the reduction of the cell s ability to concentrate particular molecules essential for biosynthesis or energy production because of defects in the permeation systems themselves, or increased leakiness of the membrane. In the case of glycerol auxotrophs of S. aureus, it has been found that the specific activity of glycine transport diminishes with time, indicating either a lack of new synthesis of the permeation system or a loss in its efficiency. ... 

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

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