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In a mitochondria, it makes ATP by using energy from NADH and FADH2 electron to pump H+ into the inter-membrane space then use the ATP synthase to bring the H+ back into the matrix while using the proton motive force to create ATP.

My question here is, why does mitochondria do this, I mean, in terms of energy I think it is a waste of energy. For example using energy to put water on the top, then generating energy by making to water come down should make some unneeded energy loss.

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  • $\begingroup$ Welcome to Biology SE! The answer to this question lies in the fact that, it would only be a waste if the mitochondria did not break even. Which it does, it uses energy to produce energy. Therefore, it isn't a waste $\endgroup$ – FoldedChromatin Aug 13 '16 at 6:29
  • $\begingroup$ Thank you for your answer! What I meant to say was that, for example, let's say that you use a water power plant to make electricity. Then use that electricity(energy) to pump water high so that you can use the water power plant to make electricity(energy). Each time you do that, you lose bits of energy, until you have no energy left. In terms of physics, it's known that when you transfer energy from A to B, you cannot transfer 100% of A's energy to B. You must lose some through heat, friction or whatever. $\endgroup$ – Danny Han Aug 13 '16 at 6:58
  • $\begingroup$ You are picturing the system as closed one. The cell by no means is a closed system. You convert, nutrients(glucose) into energy. In your analogy, the power plant should have an external source of water providing the basic minimum to drive this pumping of water so that it can produce more energy. Then it is an almost proper analogy. $\endgroup$ – FoldedChromatin Aug 13 '16 at 7:30
  • $\begingroup$ So what your saying is that, by pumping H+ in and out of the intermembrane, your creating additional energy? I don't think this true... Then, where is the extra energy coming from?? $\endgroup$ – Danny Han Aug 13 '16 at 7:32
  • $\begingroup$ I did not say that. Take a look at this image: en.wikipedia.org/wiki/Cellular_respiration#/media/… and article en.wikipedia.org/wiki/Cellular_respiration#Citric_acid_cycle $\endgroup$ – FoldedChromatin Aug 13 '16 at 7:36
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This question is actually very reasonable, and your premise is not wrong.

Certainly it's true that some potential energy is wasted in the process of creating the proton gradient (when electrons are transferred from NADH to O2) and then using the proton gradient to create ATP (by ATP synthase). And you're right, it would be much more efficient to somehow link NADH oxidation to ATP synthesis more directly. Physically, this is trivially true (and it's also true for every other series of reactions).

The problem is that biochemically, it's completely unclear how to actually do this! In fact, there was an enormous mystery about this in the field for a very long time. It was known that somehow electrons were transferred to oxygen, and that this was linked to ATP synthesis, but no one knew how the energy was transferred. People postulated that there was another high energy intermediate such as ATP, but no one was able to find such a molecule. The current theory, known as the chemiosmotic theory, was proposed in 1961 and eventually won Peter Mitchell the nobel prize (https://en.wikipedia.org/wiki/Chemiosmosis#The_chemiosmotic_theory).

If you want to take the water analogy, it's as if biology just doesn't have access to a water wheel to generate energy directly from the flowing water. But it has something that can generate electricity from water falling to the ground. So it pumps up the water, uses the tools it has to generate electricity, and accepts whatever small thermodynamic loss is associated. This is a common motif -- there simply aren't biological molecules that can catalyze every single possible chemical reaction.

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  • $\begingroup$ This answer is incorrect in accepting the poster’s premise that the two-step process wastes energy compared with a one-step process. The Gibbs free energy change for the reaction Xred + Yox + ADP + Pi → Xox + Yred + ATP is exactly the same as if one adds in the energy change of establishing a proton gradient on the left and an extra reaction exacty reversing this on the right. There is, of course, energy lost as heat in the overall process — complete efficiency is impossible, and one needs this to drive the oxidation of NADH (as with any other reaction or reaction series). $\endgroup$ – David Aug 15 '16 at 7:52
  • $\begingroup$ I disagree. For instance, consider proton leak across the membrane. $\endgroup$ – Victor Chubukov Aug 15 '16 at 12:28
  • $\begingroup$ I suggest that leakage per se through the lipid bilayer is insignificant, and that which does occur is regulated and used to maintain the basal metabolic rate of the organism. In any case the key question is waste, and thus whether a direct coupling mechanism would be able to convert more of the free energy to ATP. (No space to cover this in my last comment.) The problem with direct coupling is you can only release energy in ATP-size chunks — so in the real world there is a loss (the poster would call it a waste) in any case. Use of the electrochemical gradient may even be more flexible. $\endgroup$ – David Aug 15 '16 at 15:53
  • $\begingroup$ I don't dispute that there are other reasons why the proton gradient is incredibly useful. That would be a good alternative answer. $\endgroup$ – Victor Chubukov Aug 15 '16 at 16:14
  • $\begingroup$ I may add one later in the week when I have time. But that really requires changing the question from why? to does? Some people may not like that. $\endgroup$ – David Aug 15 '16 at 16:17
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Its because NADH is a powerful reducing agent. If you leave high concentrations of NADH in the cell, it would actually wreak havoc on the cell.

This is actually the reason why peroxisomes just remove FADH2s because they find no use for the extra energy and simply remove it.

So heres the simple answer. Energy is not always a good thing, because stability also matters. ATP is simply a good way to store and convert such energy.

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  • $\begingroup$ Thank you. Now I understand. Also after reading your answer I realized that lots of enzymes and stuff needs ATP as an energy source, which means that converting all the energy to ATP(although that might lose some energy) will be easier $\endgroup$ – Danny Han Aug 14 '16 at 2:04
  • $\begingroup$ This is nonsense. Mitochondria do NOT waste energy in the sense the questioner implied, but was unable to explain in response to my comment. Certainly not all of the free energy change is captured as ATP, but that's no different from anaerobic glycolysis. If there is sufficient ATP in the cell this decreases the reduction of NAD by regulating the relevant metabolic pathways. $\endgroup$ – David Aug 14 '16 at 7:35
  • $\begingroup$ @David what I took from the question was that why would mitochondrias not use NADH directly, as it does indeed has more free energy. Is it nonsense that NADH is a reducing agent, that it would reduce oxygens when not coupled to ATP synthesis and produce hydrogen peroxide? $\endgroup$ – Caprica Aug 14 '16 at 9:42
  • $\begingroup$ First, the premise of the question is incorrect, so any answer that accepts it is nonsense. Second there is an equilibrium between NAD and NADH in cells, and the reductive power of NADH can only be used in enzyme reactions that take the reaction over the activation energy barrier that prevents spontaneous reaction. Third the conversation of chemical energy into the electro chemical potential is one of the most sublime and beautiful things in biological chemistry. An answer that regards it as a device for preventing hydrogen peroxide formation is nonsense. $\endgroup$ – David Aug 14 '16 at 10:00
  • $\begingroup$ So you're telling me that by pointing out what would happen in case of the questioners premise was the case, that makes it nonsense? Equilibrium shouldn't be the case since I've made it clear if it was in high concentration, which would be the case of questioner's incorrect premise. So an answer that's not practical but points out what the questioner is not seeing is nonsense? There are a lot of nonsense out there but, I don't think someone else's beauty should matter in making someone else get out of their loophole? $\endgroup$ – Caprica Aug 14 '16 at 10:29

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