| [{"text": "[SQUEAKING]", "start": 0.0, "duration": 1.98}, {"text": "[RUSTLING]", "start": 1.98, "duration": 1.485}, {"text": "[CLICKING]", "start": 3.465, "duration": 6.935}, {"text": "MATTHEW VANDER\nHEIDEN: Last time, we", "start": 10.4, "duration": 1.95}, {"text": "discussed standard reduction\npotential, this E0 prime value,", "start": 12.35, "duration": 5.58}, {"text": "that really is a\nway to quantitate", "start": 17.93, "duration": 2.4}, {"text": "the propensity of a molecule\nto accept or donate electrons.", "start": 20.33, "duration": 5.61}, {"text": "And this is useful to think\nabout how energy is transduced", "start": 25.94, "duration": 4.65}, {"text": "in biological systems.", "start": 30.59, "duration": 1.23}, {"text": "Because remember, as I have\nnow tried to stress many times,", "start": 31.82, "duration": 6.57}, {"text": "how energy is moved\nthrough biology", "start": 38.39, "duration": 3.21}, {"text": "is largely about oxidation\nand reduction reactions", "start": 41.6, "duration": 4.41}, {"text": "involving carbon and\nultimately oxygen.", "start": 46.01, "duration": 3.9}, {"text": "And so remember that oxidation\nof carbon is favorable.", "start": 49.91, "duration": 6.0}, {"text": "That is removing\nelectrons from the carbon", "start": 55.91, "duration": 2.55}, {"text": "and giving them to\noxygen, exactly what we", "start": 58.46, "duration": 2.79}, {"text": "described for burning\nwood or burning gasoline.", "start": 61.25, "duration": 3.3}, {"text": "And so that's why coming\nfrom the most reduced", "start": 64.55, "duration": 3.12}, {"text": "carbon like fatty acids\nor other reduced carbon", "start": 67.67, "duration": 3.24}, {"text": "like carbohydrates,\nnot as reduced", "start": 70.91, "duration": 1.92}, {"text": "as fatty acids, that oxidizing\nthat carbon releases energy.", "start": 72.83, "duration": 6.13}, {"text": "And of course, it means\nthat storing carbon", "start": 78.96, "duration": 3.08}, {"text": "as reduced carbon either as\ncarbohydrates or fatty acids", "start": 82.04, "duration": 4.14}, {"text": "is a way to store\nenergy for later.", "start": 86.18, "duration": 3.06}, {"text": "And so moving from left to\nright, equilibrium strongly", "start": 89.24, "duration": 5.95}, {"text": "favors moving to the right.", "start": 95.19, "duration": 1.35}, {"text": "That means that delta\nG is less than 0", "start": 96.54, "duration": 3.75}, {"text": "for the oxidation of carbon.", "start": 100.29, "duration": 2.74}, {"text": "Or we can describe this\nas moving from a smaller", "start": 103.03, "duration": 3.23}, {"text": "standard reduction potential\nto a larger standard reduction", "start": 106.26, "duration": 3.78}, {"text": "potential because, remember, the\nrelationship between the change", "start": 110.04, "duration": 4.53}, {"text": "in standard reduction\npotential is related", "start": 114.57, "duration": 2.22}, {"text": "to the equilibrium\nconstant or delta G0 prime,", "start": 116.79, "duration": 4.873}, {"text": "which is also related\nto the equilibrium", "start": 121.663, "duration": 1.667}, {"text": "constant by the above formula.", "start": 123.33, "duration": 4.03}, {"text": "And so we closed last time by\nsaying that with this formula", "start": 127.36, "duration": 5.87}, {"text": "we know that, if we move from\na smaller standard reduction", "start": 133.23, "duration": 2.73}, {"text": "potential-- that is donate\nelectrons from a smaller", "start": 135.96, "duration": 2.52}, {"text": "standard reduction potential\nto a larger standard reduction", "start": 138.48, "duration": 3.39}, {"text": "potential-- that that\nnumber, that difference,", "start": 141.87, "duration": 3.96}, {"text": "will then be positive, which\nis the opposite of delta G", "start": 145.83, "duration": 5.31}, {"text": "because of that formula.", "start": 151.14, "duration": 1.07}, {"text": "And so a positive change in\nstandard reduction potential,", "start": 152.21, "duration": 2.8}, {"text": "moving from lower to\nhigher, equilibrium", "start": 155.01, "duration": 4.8}, {"text": "is going to favor\nthat direction--", "start": 159.81, "duration": 3.39}, {"text": "should make sense from\neverything we discussed before.", "start": 163.2, "duration": 4.23}, {"text": "And of course, that\nchange tells you", "start": 167.43, "duration": 1.83}, {"text": "the propensity of\nelectron transfer", "start": 169.26, "duration": 2.61}, {"text": "that ultimately is going to\nbe favorable at equilibrium.", "start": 171.87, "duration": 3.99}, {"text": "However, exactly as we\ndiscussed for delta G,", "start": 175.86, "duration": 4.68}, {"text": "whether an exact\nreaction is favorable", "start": 180.54, "duration": 2.67}, {"text": "is still going to be\ndependent on delta G.", "start": 183.21, "duration": 2.46}, {"text": "And so the change in\nstandard reduction potential", "start": 185.67, "duration": 2.43}, {"text": "tells you about the\nequilibrium constant,", "start": 188.1, "duration": 2.01}, {"text": "and so which direction\nis going to be", "start": 190.11, "duration": 2.1}, {"text": "net favorable at equilibrium.", "start": 192.21, "duration": 2.13}, {"text": "However, what actually\nhappens is still", "start": 194.34, "duration": 2.61}, {"text": "going to depend on conditions\nfor all the reasons", "start": 196.95, "duration": 2.88}, {"text": "we talked about previously.", "start": 199.83, "duration": 2.48}, {"text": "Still, this change in\nstandard reduction potential", "start": 202.31, "duration": 2.89}, {"text": "is still a useful\nconcept to think about", "start": 205.2, "duration": 3.6}, {"text": "because it tells us about\nhow energy transfer can", "start": 208.8, "duration": 3.45}, {"text": "occur across redox pairs.", "start": 212.25, "duration": 2.46}, {"text": "And that will be\nuseful in thinking", "start": 214.71, "duration": 2.7}, {"text": "about this process of\noxidative phosphorylation", "start": 217.41, "duration": 3.24}, {"text": "and how cells really couple\nelectron transfer to oxygen", "start": 220.65, "duration": 5.19}, {"text": "as a way to do lots\nof useful things", "start": 225.84, "duration": 4.23}, {"text": "in cells, including making ATP.", "start": 230.07, "duration": 4.99}, {"text": "Now, one point I want\nto come back to again,", "start": 235.06, "duration": 2.78}, {"text": "which we discussed at length\nwhen we talked about changes", "start": 237.84, "duration": 4.83}, {"text": "in free energy and how\nthat worked for pathways,", "start": 242.67, "duration": 3.51}, {"text": "is that, remember, we discussed\nthat, if we start with wood", "start": 246.18, "duration": 4.41}, {"text": "or oil and all in one\nstep burn it to CO2,", "start": 250.59, "duration": 4.02}, {"text": "it releases a certain\namount of energy.", "start": 254.61, "duration": 2.669}, {"text": "Or we can break that\ninto individual steps,", "start": 257.279, "duration": 2.641}, {"text": "as we did in glycolysis.", "start": 259.92, "duration": 2.34}, {"text": "The same amount of\nenergy is released.", "start": 262.26, "duration": 1.77}, {"text": "But by breaking into\nindividual steps,", "start": 264.03, "duration": 2.59}, {"text": "we can now capture that\nenergy as intermediates", "start": 266.62, "duration": 3.13}, {"text": "such that we can, say,\nfavorably synthesize ATP", "start": 269.75, "duration": 3.22}, {"text": "at a high ATP/ADP\nratio in cells.", "start": 272.97, "duration": 2.7}, {"text": "The exact same thing is true\nabout any of these electron", "start": 275.67, "duration": 3.18}, {"text": "transfers.", "start": 278.85, "duration": 1.2}, {"text": "There is the change in\nstandard reduction potential.", "start": 280.05, "duration": 2.82}, {"text": "Or the change in free energy\nas one moves from electron", "start": 282.87, "duration": 4.71}, {"text": "transfer from one\nacceptor to one donor", "start": 287.58, "duration": 3.09}, {"text": "is the same if\nyou go in one step", "start": 290.67, "duration": 2.4}, {"text": "or in many different steps.", "start": 293.07, "duration": 2.26}, {"text": "And so by doing these\nstepwise electron transfers", "start": 295.33, "duration": 5.02}, {"text": "in exactly the same way we\ndiscussed about for glycolysis,", "start": 300.35, "duration": 4.71}, {"text": "we can capture that energy\nrelease in smaller packets.", "start": 305.06, "duration": 3.99}, {"text": "And this is a way to basically\nbetter harness this energy", "start": 309.05, "duration": 3.45}, {"text": "release to do useful\nthings for cells.", "start": 312.5, "duration": 3.0}, {"text": "Ultimately, you'll see\nit's how you make ATP,", "start": 315.5, "duration": 1.98}, {"text": "but it can do\nother work as well,", "start": 317.48, "duration": 2.04}, {"text": "generate heat, move\nions, et cetera.", "start": 319.52, "duration": 3.24}, {"text": "And so this is really what\nI want to discuss today.", "start": 322.76, "duration": 5.28}, {"text": "But it's important to remember\nthese concepts when we think", "start": 328.04, "duration": 4.64}, {"text": "through how these systems work.", "start": 332.68, "duration": 2.34}, {"text": "And so we've now\nspent several lectures", "start": 335.02, "duration": 3.3}, {"text": "discussing the chemical\ndetails of how we can oxidize.", "start": 338.32, "duration": 4.32}, {"text": "First, we discussed\ncarbohydrates.", "start": 342.64, "duration": 1.72}, {"text": "Then we discussed fatty acids.", "start": 344.36, "duration": 2.16}, {"text": "And what we saw is that\nmany of the electrons that", "start": 346.52, "duration": 4.04}, {"text": "are lost from the\ncarbon oxidation", "start": 350.56, "duration": 3.18}, {"text": "are used to generate molecules\nsuch as NADH or FADH2", "start": 353.74, "duration": 9.09}, {"text": "and effectively charge up\na ratio, if you will, of", "start": 362.83, "duration": 6.6}, {"text": "reduce oxidized cofactors.", "start": 369.43, "duration": 3.54}, {"text": "And these molecules then donate\nthose electrons, ultimately,", "start": 372.97, "duration": 4.68}, {"text": "to oxygen. And it's that,\nhow you couple those electron", "start": 377.65, "duration": 5.61}, {"text": "transfers from these\ncarriers to oxygen,", "start": 383.26, "duration": 3.99}, {"text": "ultimately is what\noxidative phosphorylation is", "start": 387.25, "duration": 2.79}, {"text": "about as a way to allow cells\nto convert this energy released", "start": 390.04, "duration": 7.62}, {"text": "into a biologically useful form.", "start": 397.66, "duration": 3.84}, {"text": "Now, effectively,\nthe way biology", "start": 401.5, "duration": 1.86}, {"text": "does this is by using that\nfavorable electron transfer", "start": 403.36, "duration": 5.37}, {"text": "to oxygen to charge a battery.", "start": 408.73, "duration": 3.57}, {"text": "So really oxidative\nphosphorylation, if you will,", "start": 412.3, "duration": 4.87}, {"text": "is about a biological battery.", "start": 417.17, "duration": 2.52}, {"text": "And it's really\nthe same concepts", "start": 419.69, "duration": 1.98}, {"text": "that you may have\nlearned in other courses", "start": 421.67, "duration": 2.16}, {"text": "about how chemical\nbatteries work.", "start": 423.83, "duration": 2.202}, {"text": "And so let's just\nthink about that.", "start": 426.032, "duration": 1.458}, {"text": "What is a battery?", "start": 427.49, "duration": 1.71}, {"text": "Well, a battery is two different\nsolutions of ions usually", "start": 429.2, "duration": 4.59}, {"text": "that is separated\ninto two compartments.", "start": 433.79, "duration": 4.17}, {"text": "It has a unit of volts.", "start": 437.96, "duration": 4.11}, {"text": "That's exactly\nwhat the units are", "start": 442.07, "duration": 2.49}, {"text": "for this change in standard\nreduction potential is volts.", "start": 444.56, "duration": 4.7}, {"text": "By using that voltage to run\na current between the two", "start": 449.26, "duration": 4.59}, {"text": "compartments, you can do work.", "start": 453.85, "duration": 2.88}, {"text": "And if you short circuit\na battery, of course,", "start": 456.73, "duration": 3.03}, {"text": "you can get some heat.", "start": 459.76, "duration": 2.16}, {"text": "And so how are\nthese really made?", "start": 461.92, "duration": 3.54}, {"text": "Well, you basically just\nneed to get that voltage.", "start": 465.46, "duration": 3.78}, {"text": "You need to have something that\ninsulates between those two", "start": 469.24, "duration": 3.33}, {"text": "compartments.", "start": 472.57, "duration": 0.57}, {"text": "And you can then\ncontrol electron flow", "start": 473.14, "duration": 2.82}, {"text": "from one side of the\ncircuit to the other.", "start": 475.96, "duration": 3.11}, {"text": "And it's exactly the same\nissue that happens in biology,", "start": 479.07, "duration": 4.36}, {"text": "except biology\nneeds some insulator", "start": 483.43, "duration": 3.42}, {"text": "between two compartments.", "start": 486.85, "duration": 1.74}, {"text": "How do we create different\ncompartments in cells?", "start": 488.59, "duration": 2.58}, {"text": "Well, we create\nthem with membranes.", "start": 491.17, "duration": 2.62}, {"text": "And so an important function\nof membranes in cells,", "start": 493.79, "duration": 4.31}, {"text": "other than things like\nseparating cellular contents", "start": 498.1, "duration": 3.75}, {"text": "from the outside\nworld or breaking up", "start": 501.85, "duration": 2.43}, {"text": "different organelles,\nis that cells actually", "start": 504.28, "duration": 2.94}, {"text": "require a membrane.", "start": 507.22, "duration": 1.59}, {"text": "They're essential\nfor life because they", "start": 508.81, "duration": 3.51}, {"text": "are what allows an insulation\nbetween two aqueous", "start": 512.32, "duration": 4.17}, {"text": "compartments in a way\nthat you can build", "start": 516.49, "duration": 2.22}, {"text": "a biological battery that is\nreally central to how life uses", "start": 518.71, "duration": 6.3}, {"text": "energy as a way to do work.", "start": 525.01, "duration": 2.62}, {"text": "And so life creates a voltage,\nwhich I'm going to call delta", "start": 527.63, "duration": 5.66}, {"text": "psi, delta pH-- we'll come\nback to that in a little bit--", "start": 533.29, "duration": 3.03}, {"text": "to basically couple favorable\nelectron transfer from, say,", "start": 536.32, "duration": 10.36}, {"text": "an electron carrier\nlike NAD/NADH to oxygen,", "start": 546.68, "duration": 9.0}, {"text": "so reoxidizing NADH to\nreduce oxygen to water.", "start": 555.68, "duration": 6.52}, {"text": "That is moving from a lower\nto a higher standard reduction", "start": 562.2, "duration": 5.43}, {"text": "potential that's favorable.", "start": 567.63, "duration": 2.04}, {"text": "Delta G0 prime is negative.", "start": 569.67, "duration": 2.73}, {"text": "Net transfer is favorable.", "start": 572.4, "duration": 2.4}, {"text": "This can be coupled to doing\nsome work that otherwise would", "start": 574.8, "duration": 7.26}, {"text": "be unfavorable, in this\ncase pumping protons", "start": 582.06, "duration": 3.15}, {"text": "from one side of the\nmembrane to another.", "start": 585.21, "duration": 2.64}, {"text": "By pumping protons to one side\nof a membrane or the other,", "start": 587.85, "duration": 4.62}, {"text": "you create a voltage\nmembrane potential, often", "start": 592.47, "duration": 4.14}, {"text": "abbreviated delta psi.", "start": 596.61, "duration": 1.89}, {"text": "It's also a pH gradient,\nso delta H. The protons", "start": 598.5, "duration": 5.52}, {"text": "have lower pH on one side of\nthe membrane than the other.", "start": 604.02, "duration": 4.42}, {"text": "And it's this charging of a\nbattery at a membrane that", "start": 608.44, "duration": 3.86}, {"text": "is what is captured by oxidative\nphosphorylation, what's", "start": 612.3, "duration": 4.32}, {"text": "typically referred to as that\nprocess, as a way to make ATP.", "start": 616.62, "duration": 4.86}, {"text": "But of course, this\nis a useful thing.", "start": 621.48, "duration": 2.71}, {"text": "It's a battery.", "start": 624.19, "duration": 0.74}, {"text": "And so it can also do\nother work for cells.", "start": 624.93, "duration": 6.34}, {"text": "Now, I just want\nto say and really", "start": 631.27, "duration": 4.31}, {"text": "stress that this is really\ncritical, this process.", "start": 635.58, "duration": 4.65}, {"text": "And it's really central to\nhow energy works for cells.", "start": 640.23, "duration": 4.92}, {"text": "You will see that,\neffectively, this", "start": 645.15, "duration": 3.0}, {"text": "is the key steps\nin photosynthesis,", "start": 648.15, "duration": 2.88}, {"text": "do exactly the same thing.", "start": 651.03, "duration": 1.93}, {"text": "It's how mitochondria work.", "start": 652.96, "duration": 1.76}, {"text": "It's also how bacteria work.", "start": 654.72, "duration": 3.21}, {"text": "And really prokaryotes end\nup doing this at their plasma", "start": 657.93, "duration": 5.43}, {"text": "membranes, whereas mitochondria\nand chloroplasts end up", "start": 663.36, "duration": 4.86}, {"text": "doing this at intracellular\nmembranes in eukaryotes.", "start": 668.22, "duration": 4.71}, {"text": "But ultimately,\nit's the same idea", "start": 672.93, "duration": 3.24}, {"text": "of charging this biological\nbattery that really allows", "start": 676.17, "duration": 5.19}, {"text": "cells to convert, do\nenergy conversions", "start": 681.36, "duration": 4.32}, {"text": "in a way that's useful for\nthem to allow otherwise", "start": 685.68, "duration": 7.38}, {"text": "unfavorable things\nto happen in cells.", "start": 693.06, "duration": 3.66}, {"text": "Now, this works\nlargely because you", "start": 696.72, "duration": 3.81}, {"text": "have this insulating\nmembrane system, which is,", "start": 700.53, "duration": 4.26}, {"text": "of course, made of lipids.", "start": 704.79, "duration": 2.83}, {"text": "Lipids are what separates\nthe two compartments.", "start": 707.62, "duration": 2.54}, {"text": "Remember, we discussed earlier\nthat these lipid bilayers", "start": 710.16, "duration": 3.93}, {"text": "are useful because they\ncreate a hydrophobic interface", "start": 714.09, "duration": 5.67}, {"text": "between two aqueous\ncompartments.", "start": 719.76, "duration": 2.91}, {"text": "It's also useful\nbecause lipids are", "start": 722.67, "duration": 2.55}, {"text": "poor conductors of electrons.", "start": 725.22, "duration": 3.16}, {"text": "And so this really ends up\nbeing the insulating system", "start": 728.38, "duration": 5.0}, {"text": "that makes this work.", "start": 733.38, "duration": 1.99}, {"text": "Now, in the previous\nlecture, we discussed", "start": 735.37, "duration": 5.53}, {"text": "a lot about the polar\nand non-polar properties", "start": 740.9, "duration": 4.77}, {"text": "of phospholipids really\nallow them to assemble", "start": 745.67, "duration": 3.42}, {"text": "into these membrane barriers.", "start": 749.09, "duration": 2.55}, {"text": "And I just want to\ndo a slight diversion", "start": 751.64, "duration": 2.52}, {"text": "to revisit this in\nthe context of how", "start": 754.16, "duration": 2.79}, {"text": "this works for bioenergetics.", "start": 756.95, "duration": 4.72}, {"text": "So remember, you have\nthis lipid bilayer where", "start": 761.67, "duration": 4.38}, {"text": "you separate two\naqueous compartments", "start": 766.05, "duration": 13.16}, {"text": "with this hydrophobic membrane.", "start": 779.21, "duration": 2.22}, {"text": "In this membrane are\nthese phospholipids,", "start": 781.43, "duration": 6.42}, {"text": "where you have these polar head\ngroups with two lipid tails.", "start": 787.85, "duration": 5.31}, {"text": "You can look back to a\nformer lecture where I drew", "start": 793.16, "duration": 3.36}, {"text": "and we discussed what\nthose phospholipids", "start": 796.52, "duration": 3.15}, {"text": "are in great detail.", "start": 799.67, "duration": 1.71}, {"text": "But it's really having that\npolar, non-polar interface", "start": 801.38, "duration": 3.93}, {"text": "that allows you to form\nthese bilayers that's", "start": 805.31, "duration": 2.4}, {"text": "creating this separation between\nthe aqueous compartments,", "start": 807.71, "duration": 4.56}, {"text": "but also this insulator that\nallows a battery to be built", "start": 812.27, "duration": 4.83}, {"text": "across the membrane.", "start": 817.1, "duration": 3.06}, {"text": "Now, there are several\nconsequences, though,", "start": 820.16, "duration": 4.61}, {"text": "to this system that is worth\nthinking about at least", "start": 824.77, "duration": 4.23}, {"text": "in terms of how lipids\nand membranes work.", "start": 829.0, "duration": 4.83}, {"text": "Now, a consequence of\nthis is that, if we're", "start": 833.83, "duration": 2.46}, {"text": "going to create\nthis system, now we", "start": 836.29, "duration": 2.19}, {"text": "create a system where we\nhave issues with transport", "start": 838.48, "duration": 6.8}, {"text": "across from one\ncompartment to another.", "start": 845.28, "duration": 4.12}, {"text": "Now, this, of course,\nis an opportunity", "start": 849.4, "duration": 1.79}, {"text": "for a layer of regulation\nbecause it also", "start": 851.19, "duration": 4.14}, {"text": "allows then these\nconditions where", "start": 855.33, "duration": 1.65}, {"text": "you could have different\nchemical conditions,", "start": 856.98, "duration": 2.63}, {"text": "say, different ATP/ADP\nratios, NAD/NADH ratios", "start": 859.61, "duration": 3.43}, {"text": "in the different compartments,\nwhich, of course,", "start": 863.04, "duration": 2.5}, {"text": "for all the thermodynamic\nreasons we've already discussed", "start": 865.54, "duration": 2.39}, {"text": "can make things more or\nless favorable to occur", "start": 867.93, "duration": 3.33}, {"text": "in different\ncompartments in cells.", "start": 871.26, "duration": 2.67}, {"text": "But it also means\nmetabolism then", "start": 873.93, "duration": 2.1}, {"text": "has to have ways to transport\nstuff across these membranes.", "start": 876.03, "duration": 4.05}, {"text": "And we've discussed\nthis a couple of times.", "start": 880.08, "duration": 2.16}, {"text": "A few examples--\nI talked briefly", "start": 882.24, "duration": 1.92}, {"text": "about the pyruvate carrier.", "start": 884.16, "duration": 1.77}, {"text": "That is, if glycolysis\nis happening", "start": 885.93, "duration": 1.95}, {"text": "in this compartment\nin the cytosol", "start": 887.88, "duration": 2.25}, {"text": "and we need to get the pyruvate\ninside the mitochondria", "start": 890.13, "duration": 3.18}, {"text": "across a membrane for the\npyruvate dehydrogenase", "start": 893.31, "duration": 3.81}, {"text": "reaction, now you needed this\npyruvate carrier molecule.", "start": 897.12, "duration": 3.18}, {"text": "And it turns out that\nthat transport process", "start": 900.3, "duration": 1.89}, {"text": "is an opportunity\nfor regulation,", "start": 902.19, "duration": 2.01}, {"text": "but it still needs to occur.", "start": 904.2, "duration": 2.43}, {"text": "We discussed the\ncarnitine shuttle, right?", "start": 906.63, "duration": 2.73}, {"text": "Fatty acid, we generate\nfatty acyl-CoAs", "start": 909.36, "duration": 4.53}, {"text": "from breakdown of\nlipids in one side", "start": 913.89, "duration": 3.24}, {"text": "in the cytosolic compartment.", "start": 917.13, "duration": 1.38}, {"text": "We need to get those fatty\nacyl-CoAs into the mitochondria", "start": 918.51, "duration": 3.66}, {"text": "where they can be oxidized\nby fatty acid oxidation.", "start": 922.17, "duration": 2.91}, {"text": "And that required that\ncarnitine shuttle system.", "start": 925.08, "duration": 3.99}, {"text": "Now, ultimately, what mediates\nthis transport is, of course,", "start": 929.07, "duration": 5.19}, {"text": "proteins that can sit within\nthis membrane bilayer.", "start": 934.26, "duration": 6.6}, {"text": "And you can imagine\nyou can have proteins", "start": 940.86, "duration": 1.83}, {"text": "that span the\nmembrane bilayer, such", "start": 942.69, "duration": 2.19}, {"text": "that there's hydrophilic\nsurfaces that", "start": 944.88, "duration": 2.52}, {"text": "are on either face of the\nmembrane and hydrophobic", "start": 947.4, "duration": 3.93}, {"text": "residues in the middle\nwith various ways", "start": 951.33, "duration": 2.61}, {"text": "to make channels and other\ntransport mechanisms to get", "start": 953.94, "duration": 3.54}, {"text": "things from one side of\nthe membrane to the other,", "start": 957.48, "duration": 2.7}, {"text": "all right?", "start": 960.18, "duration": 0.93}, {"text": "Or you could have complexes that\nfloat freely within the lipid", "start": 961.11, "duration": 3.87}, {"text": "bilayer, such that there's\na hydrophilic surface that", "start": 964.98, "duration": 3.69}, {"text": "faces one compartment and a\nhydrophobic surface that faces", "start": 968.67, "duration": 4.2}, {"text": "the inside of the membrane.", "start": 972.87, "duration": 2.77}, {"text": "Now, having these complexes\nwill become very important", "start": 975.64, "duration": 5.21}, {"text": "for ways in which one can\nregulate processes that", "start": 980.85, "duration": 4.86}, {"text": "occur either within the\nmembrane or by moving things", "start": 985.71, "duration": 2.34}, {"text": "across membranes, like\ngenerating moving protons", "start": 988.05, "duration": 3.39}, {"text": "and generating a\nvoltage, or even", "start": 991.44, "duration": 5.91}, {"text": "move large things like\nproteins across the membrane.", "start": 997.35, "duration": 3.0}, {"text": "But it has additional\nconsequences because it now", "start": 1000.35, "duration": 4.05}, {"text": "means that the properties\nof the membrane", "start": 1004.4, "duration": 2.28}, {"text": "also matter somewhat as well.", "start": 1006.68, "duration": 2.71}, {"text": "And this brings us back\nto the other discussion", "start": 1009.39, "duration": 2.15}, {"text": "we had in the last lecture.", "start": 1011.54, "duration": 1.68}, {"text": "And that is how the various\nproperties of the fatty acids", "start": 1013.22, "duration": 4.14}, {"text": "that exist within this\nhydrophobic membrane area also,", "start": 1017.36, "duration": 6.36}, {"text": "now, can really\nmatter because they're", "start": 1023.72, "duration": 2.849}, {"text": "going to affect things\nabout how leaky this", "start": 1026.569, "duration": 3.361}, {"text": "is as an insulator between\nthe two compartments,", "start": 1029.93, "duration": 3.48}, {"text": "as well as how fluid\nthe membrane is,", "start": 1033.41, "duration": 2.28}, {"text": "such that things\nlike these proteins", "start": 1035.69, "duration": 2.429}, {"text": "can actually move within\nthis hydrophobic barrier", "start": 1038.119, "duration": 5.071}, {"text": "between the two compartments.", "start": 1043.19, "duration": 2.7}, {"text": "In other words, the fatty\nacid composition, as well as", "start": 1045.89, "duration": 13.52}, {"text": "the lipid species\nthemselves, that", "start": 1059.41, "duration": 4.29}, {"text": "is which phospholipid, other\npolar hydrophobic lipid", "start": 1063.7, "duration": 7.23}, {"text": "species analogous to\nphospholipids that form up", "start": 1070.93, "duration": 3.72}, {"text": "membranes, can change\nproperties such as how leaky", "start": 1074.65, "duration": 4.35}, {"text": "the membrane is or how\nfluid the membrane is.", "start": 1079.0, "duration": 6.03}, {"text": "You can imagine, if you have a\nreally rigid membrane surface,", "start": 1085.03, "duration": 4.35}, {"text": "you're not going to get\nany flow of materials.", "start": 1089.38, "duration": 3.25}, {"text": "It's not going to be very\nleaky, which might be great", "start": 1092.63, "duration": 2.538}, {"text": "if you want to build an\ninsulator between the two", "start": 1095.168, "duration": 2.042}, {"text": "compartments.", "start": 1097.21, "duration": 0.96}, {"text": "But it's going to be very\ndifficult to regulate transport", "start": 1098.17, "duration": 3.42}, {"text": "across that compartment.", "start": 1101.59, "duration": 1.68}, {"text": "And so nature has come up with\na bunch of different solutions", "start": 1103.27, "duration": 3.72}, {"text": "for how to play with fatty acid\nand other lipid composition", "start": 1106.99, "duration": 5.01}, {"text": "to change the\nproperties of membranes.", "start": 1112.0, "duration": 2.49}, {"text": "We don't have time to get\ninto that in great detail", "start": 1114.49, "duration": 2.58}, {"text": "in this course, but I\nwant you to appreciate", "start": 1117.07, "duration": 1.89}, {"text": "that these things exist.", "start": 1118.96, "duration": 1.92}, {"text": "But one thing I want to\ndiscuss is that often,", "start": 1120.88, "duration": 2.58}, {"text": "when you see phospholipids\ndrawn like this,", "start": 1123.46, "duration": 3.15}, {"text": "they're drawn in this\nway where the polar head", "start": 1126.61, "duration": 2.07}, {"text": "group is a circle.", "start": 1128.68, "duration": 1.47}, {"text": "And then they'll draw the\ntwo lipids tails often", "start": 1130.15, "duration": 3.51}, {"text": "with a kink in one\nof the lipid tails.", "start": 1133.66, "duration": 2.37}, {"text": "That's because many times\nphospholipids, of the two lipid", "start": 1136.03, "duration": 3.12}, {"text": "tails, one is saturated.", "start": 1139.15, "duration": 2.31}, {"text": "And one has a\nmonounsaturation in it.", "start": 1141.46, "duration": 4.32}, {"text": "And I just want to go\nback to the models here.", "start": 1145.78, "duration": 2.85}, {"text": "Remember, the monounsaturated,\nthe double bond,", "start": 1148.63, "duration": 2.94}, {"text": "ends up being this\ncis double bond.", "start": 1151.57, "duration": 3.22}, {"text": "And so here's two fatty acids.", "start": 1154.79, "duration": 3.98}, {"text": "If you put these here in with\nthe head groups on one side--", "start": 1158.77, "duration": 4.5}, {"text": "so this would be esterified to\nthe glycerol, the phospholipid,", "start": 1163.27, "duration": 3.63}, {"text": "you end up getting this\nkink in the membrane, which", "start": 1166.9, "duration": 2.85}, {"text": "is much different than\ntwo straight chains.", "start": 1169.75, "duration": 2.82}, {"text": "You can imagine that\nwithin the membrane", "start": 1172.57, "duration": 1.89}, {"text": "itself this ends up basically\nnot letting those lipid tails", "start": 1174.46, "duration": 5.22}, {"text": "pack quite so tightly in the\nmembrane, which certainly", "start": 1179.68, "duration": 3.48}, {"text": "contributes to an\nability to have space", "start": 1183.16, "duration": 3.93}, {"text": "to put other stuff in\nthe membrane to allow", "start": 1187.09, "duration": 2.58}, {"text": "other processes to happen.", "start": 1189.67, "duration": 2.85}, {"text": "Now, recall that\nthere's other ways", "start": 1192.52, "duration": 2.67}, {"text": "we can modulate the\nproperties of fatty acids,", "start": 1195.19, "duration": 6.02}, {"text": "introduce more double bonds,\nchain length, et cetera.", "start": 1201.21, "duration": 4.45}, {"text": "And different organisms\nuse different strategies", "start": 1205.66, "duration": 3.89}, {"text": "to deal with this.", "start": 1209.55, "duration": 1.48}, {"text": "And so plants,\nremember, have all kinds", "start": 1211.03, "duration": 4.79}, {"text": "of polyunsaturated fatty acids,\njust like we talked about", "start": 1215.82, "duration": 5.1}, {"text": "with plant oils being\nliquid at room temperature.", "start": 1220.92, "duration": 3.36}, {"text": "Having more polyunsaturated\nfatty acids in their lipid", "start": 1224.28, "duration": 5.58}, {"text": "tails is one way\nplants use to keep", "start": 1229.86, "duration": 4.17}, {"text": "their membranes more fluid.", "start": 1234.03, "duration": 2.58}, {"text": "Animals, remember, have\nmore saturated fatty acids.", "start": 1236.61, "duration": 4.08}, {"text": "All right, those\nsaturated fatty acids--", "start": 1240.69, "duration": 3.6}, {"text": "less double bonds, going\nto be higher melting", "start": 1244.29, "duration": 3.9}, {"text": "temperature, more likely to\nbe solid at room temperature.", "start": 1248.19, "duration": 3.94}, {"text": "So that's not going to be very\ngood for membrane fluidity.", "start": 1252.13, "duration": 2.54}, {"text": "And it turns out animals\nuse a different strategy", "start": 1254.67, "duration": 3.72}, {"text": "to keep membrane\nfluidity that's not", "start": 1258.39, "duration": 2.16}, {"text": "polyunsaturated fatty acids.", "start": 1260.55, "duration": 2.13}, {"text": "And that is that they\nincorporate this molecule shown", "start": 1262.68, "duration": 3.15}, {"text": "here on the slide,\nwhich is cholesterol,", "start": 1265.83, "duration": 3.7}, {"text": "which you're well aware of.", "start": 1269.53, "duration": 1.5}, {"text": "And so animals use you\nsterols, like cholesterol,", "start": 1271.03, "duration": 4.04}, {"text": "as a way to keep their\nmembranes more fluid.", "start": 1275.07, "duration": 4.3}, {"text": "And so that cholesterol that\nis present in animal products", "start": 1279.37, "duration": 5.33}, {"text": "is not there to give\nyou heart attacks.", "start": 1284.7, "duration": 2.05}, {"text": "It's really there\nas a way animals use", "start": 1286.75, "duration": 2.57}, {"text": "to keep their membranes fluid.", "start": 1289.32, "duration": 2.13}, {"text": "And this is really,\nat heart, why", "start": 1291.45, "duration": 2.19}, {"text": "plants are cholesterol\nfree foods and animals have", "start": 1293.64, "duration": 3.93}, {"text": "cholesterol.", "start": 1297.57, "duration": 1.08}, {"text": "And it's because animals\nuse cholesterol as a way", "start": 1298.65, "duration": 2.88}, {"text": "to keep their membranes\nfluid, whereas plants", "start": 1301.53, "duration": 2.34}, {"text": "use a different strategy,\npolyunsaturated fatty acids.", "start": 1303.87, "duration": 5.1}, {"text": "All right, now,\nultimately setting up", "start": 1308.97, "duration": 5.12}, {"text": "the system this way is\nimportant because it allows", "start": 1314.09, "duration": 3.63}, {"text": "for these flexible\nmembranes that", "start": 1317.72, "duration": 1.68}, {"text": "can enable ion and other\ntransport between compartments,", "start": 1319.4, "duration": 4.53}, {"text": "as well as hold a charge so that\nyou can form this battery which", "start": 1323.93, "duration": 6.72}, {"text": "allows oxidative phosphorylation\nor other processes to occur", "start": 1330.65, "duration": 4.17}, {"text": "where you can\ncharge this membrane", "start": 1334.82, "duration": 2.25}, {"text": "and ultimately use that\nvoltage to do work,", "start": 1337.07, "duration": 5.67}, {"text": "like make ATP, all right?", "start": 1342.74, "duration": 3.39}, {"text": "Now, how this membrane\ncharging occurs,", "start": 1346.13, "duration": 5.32}, {"text": "again, is really taking\nadvantage of favorable electron", "start": 1351.45, "duration": 4.86}, {"text": "transfer across a\nseries of redox pairs,", "start": 1356.31, "duration": 4.8}, {"text": "ultimately, to oxygen or\nanother good electron acceptor.", "start": 1361.11, "duration": 4.86}, {"text": "And it's really that\nfavorable electron transfer", "start": 1365.97, "duration": 3.48}, {"text": "that's being coupled to\nthis pumping of proton ions", "start": 1369.45, "duration": 3.93}, {"text": "to charge a battery.", "start": 1373.38, "duration": 2.19}, {"text": "That's the oxidation part.", "start": 1375.57, "duration": 2.16}, {"text": "And then that battery doing work\nsuch as driving favorable ADP", "start": 1377.73, "duration": 6.48}, {"text": "to ATP conversion,\nthe phosphorylation", "start": 1384.21, "duration": 3.93}, {"text": "part of oxidative\nphosphorylation,", "start": 1388.14, "duration": 2.91}, {"text": "is the type of work\nthat you can then", "start": 1391.05, "duration": 3.57}, {"text": "do once you generate this\nchemical battery, although not", "start": 1394.62, "duration": 4.17}, {"text": "the only work you can\ndo with that battery.", "start": 1398.79, "duration": 2.13}, {"text": "And it's why this\nis so much more", "start": 1400.92, "duration": 1.41}, {"text": "flexible than just making ATP.", "start": 1402.33, "duration": 3.83}, {"text": "All right, so\nultimately this process", "start": 1406.16, "duration": 5.67}, {"text": "by coupling transfer\nof electrons", "start": 1411.83, "duration": 3.69}, {"text": "from favorable\noxidation of carbon", "start": 1415.52, "duration": 2.34}, {"text": "to charge up these other\nelectron carriers that", "start": 1417.86, "duration": 3.51}, {"text": "ultimately transfer to\noxygen is a major way", "start": 1421.37, "duration": 5.37}, {"text": "that life uses nutrient\noxidation to convert it", "start": 1426.74, "duration": 5.61}, {"text": "to biologically useful energy.", "start": 1432.35, "duration": 2.46}, {"text": "And this is where we get to this\nprocess of what is typically", "start": 1434.81, "duration": 4.44}, {"text": "referred to as oxidative\nphosphorylation, which", "start": 1439.25, "duration": 8.28}, {"text": "is a concept or a process that\nwas often abbreviated oxphos.", "start": 1447.53, "duration": 7.32}, {"text": "And it was discovered by or\nfirst described by a gentleman", "start": 1454.85, "duration": 4.5}, {"text": "by the name of Peter Mitchell.", "start": 1459.35, "duration": 1.44}, {"text": "And like many novel or\nrevolutionary ideas,", "start": 1464.59, "duration": 4.56}, {"text": "when Peter Mitchell first\ndescribed or proposed", "start": 1469.15, "duration": 3.09}, {"text": "the processes I'm about\nto tell you about,", "start": 1472.24, "duration": 2.1}, {"text": "his ideas were\ninitially dismissed.", "start": 1474.34, "duration": 4.26}, {"text": "It was thought at the time, when\npeople were thinking about how", "start": 1478.6, "duration": 3.3}, {"text": "do you couple metabolism to,\nsay, charge up your ATP/ADP", "start": 1481.9, "duration": 3.93}, {"text": "ratio, that that\nprocess would work", "start": 1485.83, "duration": 3.45}, {"text": "via the oxidative\nphosphorylation type reactions", "start": 1489.28, "duration": 4.35}, {"text": "that we otherwise\ndescribed, things", "start": 1493.63, "duration": 2.28}, {"text": "like what happens at the GAPDH\nstep or the succinic thiokinase", "start": 1495.91, "duration": 3.75}, {"text": "step in the TCA cycle.", "start": 1499.66, "duration": 2.1}, {"text": "Those are two examples\nwhere we could directly", "start": 1501.76, "duration": 2.58}, {"text": "couple the oxidation of carbon\nto a phosphorylation event that", "start": 1504.34, "duration": 6.48}, {"text": "ultimately allowed us\nto favorably produce", "start": 1510.82, "duration": 3.72}, {"text": "ATP to maintain an\nATP/ADP ratio that's high", "start": 1514.54, "duration": 5.52}, {"text": "and is present in cells.", "start": 1520.06, "duration": 3.03}, {"text": "However, what Peter\nMitchell described", "start": 1523.09, "duration": 2.67}, {"text": "was really this\nbattery phenomena", "start": 1525.76, "duration": 3.45}, {"text": "that we're talking about.", "start": 1529.21, "duration": 1.54}, {"text": "And it turned out\nto be largely right", "start": 1530.75, "duration": 2.75}, {"text": "and represents something\nthat's actually", "start": 1533.5, "duration": 2.88}, {"text": "quite unique about\nbiological processes", "start": 1536.38, "duration": 4.23}, {"text": "even if you think about other\nbiological processes that", "start": 1540.61, "duration": 2.64}, {"text": "occur.", "start": 1543.25, "duration": 0.84}, {"text": "And that is what he\nproposed was the oxidation", "start": 1544.09, "duration": 6.45}, {"text": "and phosphorylation events were\nactually separate processes.", "start": 1550.54, "duration": 13.72}, {"text": "That is nature does not have\nto have these two things touch", "start": 1564.26, "duration": 5.07}, {"text": "in order for them to work.", "start": 1569.33, "duration": 2.04}, {"text": "That is that you use\noxidation to create", "start": 1571.37, "duration": 5.1}, {"text": "this battery as one event.", "start": 1576.47, "duration": 2.31}, {"text": "So oxidation generates this\npotential across a membrane.", "start": 1583.56, "duration": 12.9}, {"text": "And then that potential\nacross a membrane", "start": 1596.46, "duration": 3.93}, {"text": "is a totally separate event,\ncan drive phosphorylation, ATP,", "start": 1600.39, "duration": 22.24}, {"text": "or do other work,\nultimately making", "start": 1622.63, "duration": 2.46}, {"text": "this a more flexible\nsystem for biology.", "start": 1625.09, "duration": 3.69}, {"text": "And so turns out, as I said\nbefore, in a prokaryotic cell--", "start": 1628.78, "duration": 5.26}, {"text": "so this here is some\nkind of prokaryote, OK?", "start": 1634.04, "duration": 6.44}, {"text": "Prokaryotes have a membrane\nthat separates them", "start": 1640.48, "duration": 3.15}, {"text": "from the outside world.", "start": 1643.63, "duration": 1.24}, {"text": "This cell membrane effectively\ncouples that oxidation step", "start": 1644.87, "duration": 5.75}, {"text": "to the pumping of protons.", "start": 1650.62, "duration": 1.95}, {"text": "That creates a battery\nat the cell membrane", "start": 1652.57, "duration": 9.2}, {"text": "of the prokaryote.", "start": 1661.77, "duration": 1.65}, {"text": "And separate in\nspace, that can then", "start": 1663.42, "duration": 4.11}, {"text": "be used to drive\nATP synthesis or do", "start": 1667.53, "duration": 5.91}, {"text": "other work that's useful to\nmaintain that prokaryotic cell.", "start": 1673.44, "duration": 6.98}, {"text": "Now, in eukaryotes, this\nprocess occurs at membranes", "start": 1680.42, "duration": 9.52}, {"text": "within the mitochondria.", "start": 1689.94, "duration": 1.24}, {"text": "So this here is a\nmitochondria, OK?", "start": 1691.18, "duration": 3.71}, {"text": "So just to remind you of some\nvery basic cell biology--", "start": 1694.89, "duration": 6.12}, {"text": "and so, remember, mitochondria\nhave two membranes.", "start": 1701.01, "duration": 3.13}, {"text": "So there's this outer\nmitochondrial membrane,", "start": 1704.14, "duration": 10.94}, {"text": "outer mitochondrial membrane.", "start": 1715.08, "duration": 1.98}, {"text": "And then there's this inner\nmitochondrial membrane,", "start": 1717.06, "duration": 7.14}, {"text": "so two membranes in\nthe mitochondria.", "start": 1724.2, "duration": 2.73}, {"text": "Remember, there's\nthis matrix space.", "start": 1726.93, "duration": 5.45}, {"text": "The cytosol would be out here.", "start": 1732.38, "duration": 2.64}, {"text": "And then there's this space\nbetween the two membranes", "start": 1735.02, "duration": 4.23}, {"text": "called the intermembrane\nspace, intermembrane space", "start": 1739.25, "duration": 15.18}, {"text": "between the two membranes.", "start": 1754.43, "duration": 2.26}, {"text": "If you'll recall, many of these\noxidation reactions, the TCA", "start": 1756.69, "duration": 5.0}, {"text": "cycle, fatty acid oxidation,\npyruvate dehydrogenase step,", "start": 1761.69, "duration": 5.07}, {"text": "all of those were happening in\nthe matrix of the mitochondria.", "start": 1766.76, "duration": 4.08}, {"text": "Remember, glycolysis\nwas in the cytosol,", "start": 1770.84, "duration": 2.55}, {"text": "but all these other\nprocesses were", "start": 1773.39, "duration": 2.07}, {"text": "happening in the matrix\nof the mitochondria.", "start": 1775.46, "duration": 2.37}, {"text": "And really what's going\non is that this battery is", "start": 1777.83, "duration": 4.11}, {"text": "being charged across this inner\nmitochondrial membrane, OK?", "start": 1781.94, "duration": 4.98}, {"text": "So protons are being pumped\ninto the inner mitochondrial", "start": 1786.92, "duration": 3.63}, {"text": "membrane into the intermembrane\nspace of the mitochondria", "start": 1790.55, "duration": 5.13}, {"text": "and then used to synthesize\nATP in the matrix", "start": 1795.68, "duration": 5.49}, {"text": "of the mitochondria.", "start": 1801.17, "duration": 1.92}, {"text": "Now, part of this came,\nmany people know-- remember,", "start": 1803.09, "duration": 3.96}, {"text": "mitochondria have their\nown DNA, et cetera.", "start": 1807.05, "duration": 2.59}, {"text": "And so really where\npeople thought,", "start": 1809.64, "duration": 2.9}, {"text": "think eukaryotic cells\ncame from is basically", "start": 1812.54, "duration": 3.36}, {"text": "the mitochondria is an enslaved\nbacteria or an obligate", "start": 1815.9, "duration": 5.16}, {"text": "captured symbiont, if you\nwill, where one cell engulfed", "start": 1821.06, "duration": 4.98}, {"text": "a different prokaryotic cell.", "start": 1826.04, "duration": 2.44}, {"text": "And if you track this, think\nof the inner mitochondrial", "start": 1828.48, "duration": 6.13}, {"text": "membrane as a enslaved\nprokaryotic cell,", "start": 1834.61, "duration": 4.68}, {"text": "you can see that\nyou're generating", "start": 1839.29, "duration": 1.8}, {"text": "this membrane potential\nacross the inner mitochondrial", "start": 1841.09, "duration": 10.35}, {"text": "membrane, which is\nreally equivalent", "start": 1851.44, "duration": 2.22}, {"text": "to the bacterial membrane of\nthe enslaved prokaryotic cell.", "start": 1853.66, "duration": 5.67}, {"text": "In both cases, it's\ncreating this battery", "start": 1859.33, "duration": 3.66}, {"text": "at a membrane, the inner\nmitochondrial membrane", "start": 1862.99, "duration": 2.55}, {"text": "or the bacterial membrane of\na prokaryote, that is then", "start": 1865.54, "duration": 3.09}, {"text": "being used to\nseparately in space", "start": 1868.63, "duration": 4.2}, {"text": "use that gradient to do\nwork, such as synthesize ATP.", "start": 1872.83, "duration": 4.53}, {"text": "So if I draw this more\nexplicitly as this here", "start": 1881.41, "duration": 7.84}, {"text": "being the membrane--", "start": 1889.25, "duration": 1.84}, {"text": "so the inner\nmitochondrial membrane", "start": 1891.09, "duration": 4.87}, {"text": "of a mitochondria or\nthe bacterial membrane", "start": 1895.96, "duration": 9.64}, {"text": "of a prokaryotic\ncell, such that this", "start": 1905.6, "duration": 2.49}, {"text": "is outside the bacteria,\nthat's inside the bacteria.", "start": 1908.09, "duration": 3.88}, {"text": "This is the intermembrane\nspace often referred to", "start": 1911.97, "duration": 4.13}, {"text": "as the cytosol side.", "start": 1916.1, "duration": 2.49}, {"text": "Of course, there's another outer\nmitochondrial membrane here", "start": 1918.59, "duration": 3.27}, {"text": "that, for the sake\nof this class,", "start": 1921.86, "duration": 2.53}, {"text": "you can just think of as\nbeing generally permeable.", "start": 1924.39, "duration": 3.18}, {"text": "This would be the matrix inside\nof the inner mitochondrial", "start": 1927.57, "duration": 3.29}, {"text": "membrane.", "start": 1930.86, "duration": 1.12}, {"text": "And so all this NADH\nis being generated", "start": 1931.98, "duration": 7.34}, {"text": "from nutrient\noxidation TCA cycle,", "start": 1939.32, "duration": 3.06}, {"text": "fatty acid oxidation,\npyruvate dehydrogenase,", "start": 1942.38, "duration": 2.31}, {"text": "whatever, within the matrix\nor within the bacteria.", "start": 1944.69, "duration": 3.33}, {"text": "Those electrons are ultimately\nbeing transferred from NADH,", "start": 1952.43, "duration": 6.93}, {"text": "reoxidizing it to NAD, to\nreduce oxygen to water.", "start": 1959.36, "duration": 6.37}, {"text": "This is favorable.", "start": 1965.73, "duration": 2.64}, {"text": "This is, therefore,\ncoupled to pumping protons.", "start": 1968.37, "duration": 6.84}, {"text": "That creates a membrane\npotential and gradient", "start": 1975.21, "duration": 9.65}, {"text": "across this membrane,\nwhich can be", "start": 1984.86, "duration": 4.17}, {"text": "used to do work such as\ndriving the synthesis of ATP", "start": 1989.03, "duration": 13.91}, {"text": "for other work.", "start": 2002.94, "duration": 1.63}, {"text": "So this all has to happen\nat the same membrane,", "start": 2004.57, "duration": 4.0}, {"text": "but this process does not\nhave to touch that process.", "start": 2008.57, "duration": 4.79}, {"text": "It's coupled because\nyou create this battery,", "start": 2013.36, "duration": 3.3}, {"text": "this membrane potential\nand pH gradient, that", "start": 2016.66, "duration": 5.52}, {"text": "can be used elsewhere\nalong the membrane", "start": 2022.18, "duration": 3.39}, {"text": "to do some kind of work.", "start": 2025.57, "duration": 3.29}, {"text": "Now, I draw this is\ndelta psi, delta pH.", "start": 2028.86, "duration": 2.48}, {"text": "You can imagine, if\nyou're moving protons,", "start": 2031.34, "duration": 2.41}, {"text": "you're going to\ncreate a voltage.", "start": 2033.75, "duration": 2.67}, {"text": "You're also going to\ncreate a pH gradient.", "start": 2036.42, "duration": 2.552}, {"text": "It turns out I don't\nhave time to discuss", "start": 2038.972, "duration": 1.708}, {"text": "this further in the class.", "start": 2040.68, "duration": 1.083}, {"text": "A lot is written\nabout how to think", "start": 2041.763, "duration": 2.307}, {"text": "about this membrane potential\nas either a true voltage", "start": 2044.07, "duration": 5.25}, {"text": "or as a pH gradient.", "start": 2049.32, "duration": 1.62}, {"text": "It turns out that\nthey're useful to think", "start": 2050.94, "duration": 1.949}, {"text": "about in different ways\nfor different processes.", "start": 2052.889, "duration": 2.895}, {"text": "But if you're\ninterested in this,", "start": 2055.784, "duration": 1.375}, {"text": "there's certainly lots written\nabout this on various papers", "start": 2057.159, "duration": 4.131}, {"text": "and texts on bioenergetics.", "start": 2061.29, "duration": 2.099}, {"text": "And I would encourage you\nto read more about that.", "start": 2063.389, "duration": 3.491}, {"text": "OK.", "start": 2066.88, "duration": 1.255}, {"text": "All right, what\nI want to do next", "start": 2068.135, "duration": 1.375}, {"text": "then is discuss each\nof these processes", "start": 2069.51, "duration": 3.03}, {"text": "in turn, that is\nhow does this work", "start": 2072.54, "duration": 2.31}, {"text": "and how does that work,\nto really understand", "start": 2074.85, "duration": 6.17}, {"text": "what's going on in\nmitochondria and bacteria", "start": 2081.02, "duration": 3.719}, {"text": "to carry out this process of\noxidative phosphorylation.", "start": 2084.739, "duration": 4.631}, {"text": "So first, let's talk here.", "start": 2089.37, "duration": 1.91}, {"text": "First, how does one use\nfavorable electron transfer", "start": 2091.28, "duration": 14.91}, {"text": "to make this membrane potential?", "start": 2106.19, "duration": 10.4}, {"text": "Obviously, if we're\ngoing to pump protons", "start": 2116.59, "duration": 3.27}, {"text": "against a gradient, such that\nwe have different concentration", "start": 2119.86, "duration": 4.92}, {"text": "of protons on either\nside of the membrane,", "start": 2124.78, "duration": 2.01}, {"text": "that's going to\nrequire energy input.", "start": 2126.79, "duration": 2.64}, {"text": "And that energy is going to\ncome from favorable electron", "start": 2129.43, "duration": 3.91}, {"text": "transfer.", "start": 2133.34, "duration": 0.5}, {"text": "And really this process is\ntaking electrons from, say,", "start": 2136.65, "duration": 12.84}, {"text": "a cofactor like NADH, and\nultimately transferring", "start": 2149.49, "duration": 10.64}, {"text": "those electrons to\noxygen to get water.", "start": 2160.13, "duration": 5.05}, {"text": "The standard reduction\npotential of NAD/NADH", "start": 2165.18, "duration": 4.14}, {"text": "is less than the\nstandard reduction", "start": 2169.32, "duration": 2.7}, {"text": "potential of oxygen and water.", "start": 2172.02, "duration": 2.22}, {"text": "That means that equilibrium\nis going to favor electron", "start": 2174.24, "duration": 3.78}, {"text": "transport in this direction.", "start": 2178.02, "duration": 2.4}, {"text": "To say it another way,\nrelative to oxygen-water,", "start": 2180.42, "duration": 4.75}, {"text": "NAD/NADH is a better\nelectron donor.", "start": 2185.17, "duration": 2.96}, {"text": "Oxygen-water is a better\nelectron acceptor pair.", "start": 2188.13, "duration": 4.35}, {"text": "And so by this electron\ntransfer being favorable,", "start": 2192.48, "duration": 4.98}, {"text": "it can be used then\nto release energy", "start": 2197.46, "duration": 5.31}, {"text": "coupled to other processes,\nsuch as moving protons", "start": 2202.77, "duration": 3.99}, {"text": "and make that otherwise\nunfavorable process favorable.", "start": 2206.76, "duration": 4.77}, {"text": "Now, you'll note\nthat, in doing this,", "start": 2211.53, "duration": 3.6}, {"text": "we now regenerate the\noxidized cofactor NAD+.", "start": 2215.13, "duration": 4.38}, {"text": "And so that solves our electron\nbalance problem for glycolysis,", "start": 2219.51, "duration": 5.49}, {"text": "solves any electron\nbalance problem", "start": 2225.0, "duration": 2.91}, {"text": "that would exist for fatty\nacid oxidation or the TCA cycle", "start": 2227.91, "duration": 4.47}, {"text": "in the mitochondria.", "start": 2232.38, "duration": 1.47}, {"text": "Because ultimately,\nthose electrons", "start": 2233.85, "duration": 1.77}, {"text": "are being given to\noxygen. And so oxygen,", "start": 2235.62, "duration": 3.18}, {"text": "being this final\nelectron acceptor,", "start": 2238.8, "duration": 3.23}, {"text": "being stoichiometrically\nproduced to generate water,", "start": 2242.03, "duration": 4.59}, {"text": "is effectively water being\nthe alternative waste product", "start": 2246.62, "duration": 3.93}, {"text": "to, say, lactate\nor ethanol that we", "start": 2250.55, "duration": 2.07}, {"text": "saw in fermentation, all right?", "start": 2252.62, "duration": 3.9}, {"text": "Now, as we started the\nlecture with and discussed", "start": 2256.52, "duration": 2.76}, {"text": "in glycolysis, if we do this\nin one step, it's favorable.", "start": 2259.28, "duration": 3.84}, {"text": "But it's also favorable if we\ndo it in lots of little steps.", "start": 2263.12, "duration": 5.49}, {"text": "By doing it and lots\nof little steps,", "start": 2268.61, "duration": 1.96}, {"text": "just like we did\nin glycolysis, we", "start": 2270.57, "duration": 2.24}, {"text": "can break up that\nenergy release in a way", "start": 2272.81, "duration": 2.37}, {"text": "to allow us to do\nmore work, right?", "start": 2275.18, "duration": 2.88}, {"text": "So in glycolysis, we could\nturn carbohydrate into CO2--", "start": 2278.06, "duration": 6.62}, {"text": "one step, burning wood,\nrelease a lot of light and heat", "start": 2284.68, "duration": 3.24}, {"text": "all in one step.", "start": 2287.92, "duration": 1.59}, {"text": "That can be used to do work.", "start": 2289.51, "duration": 1.59}, {"text": "But it was more efficient to\nbreak it up into little steps", "start": 2291.1, "duration": 3.0}, {"text": "where we could then\ncapture intermediates", "start": 2294.1, "duration": 1.8}, {"text": "that made ATP synthase favorable\ndespite high ATP/ADP ratio.", "start": 2295.9, "duration": 4.95}, {"text": "Same idea here, we could\ntransfer this all in one step.", "start": 2300.85, "duration": 3.45}, {"text": "But instead, you break\nit up into a bunch", "start": 2304.3, "duration": 2.07}, {"text": "of individual steps, which can\nthen be coupled individually", "start": 2306.37, "duration": 4.68}, {"text": "to pumping protons\nacross the membrane", "start": 2311.05, "duration": 2.44}, {"text": "to generate more efficiently\nthis delta PSI delta pH", "start": 2313.49, "duration": 4.49}, {"text": "to charge this battery.", "start": 2317.98, "duration": 2.28}, {"text": "And so this occurs across a\nseries of electron carriers,", "start": 2320.26, "duration": 6.36}, {"text": "multi-protein complexes,\nelectron carriers,", "start": 2326.62, "duration": 3.24}, {"text": "called the electron\ntransport chain.", "start": 2329.86, "duration": 2.79}, {"text": "And you can think of this\nelectron transport chain", "start": 2335.75, "duration": 2.72}, {"text": "as being entirely analogous\nto what we already", "start": 2338.47, "duration": 2.85}, {"text": "talked about when\nwe talked about how", "start": 2341.32, "duration": 2.34}, {"text": "pyruvate dehydrogenase\nor alpha-ketoglutarate", "start": 2343.66, "duration": 2.43}, {"text": "dehydrogenase works when we\ntalked about the TCA cycle.", "start": 2346.09, "duration": 3.24}, {"text": "Remember, these had these\ndifferent protein complexes,", "start": 2349.33, "duration": 3.15}, {"text": "this E1, E2, E3,\nwhere electrons were", "start": 2352.48, "duration": 2.94}, {"text": "transferred across this chain.", "start": 2355.42, "duration": 1.83}, {"text": "It's exactly the same\nidea here, a number", "start": 2357.25, "duration": 2.76}, {"text": "of multi-polypeptide\nencoded protein complexes", "start": 2360.01, "duration": 4.89}, {"text": "that come together to hold\na bunch of electron carriers", "start": 2364.9, "duration": 4.86}, {"text": "that break up the energy\nrelease, if you will,", "start": 2369.76, "duration": 3.64}, {"text": "as we oxidize NADH and\nreduce oxygen and transfer", "start": 2373.4, "duration": 5.48}, {"text": "those electrons along the chain\nwith the complexes themselves", "start": 2378.88, "duration": 4.56}, {"text": "coupling the favorable\nelectron transfer to the moving", "start": 2383.44, "duration": 3.6}, {"text": "of protons against a gradient\nacross the membrane to work.", "start": 2387.04, "duration": 5.0}, {"text": "And so for this electron\ntransport chain to work,", "start": 2392.04, "duration": 3.66}, {"text": "we obviously need a bunch\nof electron carriers.", "start": 2395.7, "duration": 3.3}, {"text": "And why you need more\nthan one electron carrier", "start": 2399.0, "duration": 2.22}, {"text": "should now be obvious.", "start": 2401.22, "duration": 1.53}, {"text": "Because having\ndifferent carriers that", "start": 2402.75, "duration": 2.52}, {"text": "sit at different\nstandard reduction", "start": 2405.27, "duration": 2.88}, {"text": "potentials is going\nto be useful if we", "start": 2408.15, "duration": 4.23}, {"text": "want to build a chain such that\nwe can have favorable oxidation", "start": 2412.38, "duration": 5.88}, {"text": "and reduction to move electrons\nin a favorable direction", "start": 2418.26, "duration": 3.54}, {"text": "and couple that to\nprocesses that allow", "start": 2421.8, "duration": 4.41}, {"text": "us to charge this battery.", "start": 2426.21, "duration": 2.76}, {"text": "And so it turns out that\nfor this electron transport", "start": 2428.97, "duration": 2.85}, {"text": "chain to work--", "start": 2431.82, "duration": 1.38}, {"text": "well, we know about some\nof our electron carriers.", "start": 2433.2, "duration": 2.47}, {"text": "So we've discussed NAD, NADH.", "start": 2435.67, "duration": 4.22}, {"text": "There's FAD, FADH2.", "start": 2439.89, "duration": 3.38}, {"text": "There was lipoic acid.", "start": 2443.27, "duration": 1.2}, {"text": "Lipoic acid is not part of\nthe electron transport chain.", "start": 2447.8, "duration": 5.66}, {"text": "NAD, NADH is a donor.", "start": 2453.46, "duration": 1.43}, {"text": "You'll see FAD can be part of\nthe electron transport chain,", "start": 2454.89, "duration": 4.2}, {"text": "but there's a different--", "start": 2459.09, "duration": 1.65}, {"text": "or there's additional\nelectron carriers.", "start": 2460.74, "duration": 1.77}, {"text": "I want to discuss those now.", "start": 2462.51, "duration": 2.65}, {"text": "So another important\none is something called", "start": 2465.16, "duration": 2.81}, {"text": "FMN or Flavin Mononucleotide.", "start": 2467.97, "duration": 5.636}, {"text": "What FMN, or Flavin\nMononucleotide is, is it's", "start": 2476.89, "duration": 4.47}, {"text": "effectively FAD.", "start": 2481.36, "duration": 2.91}, {"text": "But it's a FAD not in\na dinucleotide state,", "start": 2484.27, "duration": 3.48}, {"text": "but a mononucleotide state.", "start": 2487.75, "duration": 2.2}, {"text": "So if you take FAD and you\nremove an AMP group from it,", "start": 2489.95, "duration": 3.68}, {"text": "what you're left with is FMN.", "start": 2493.63, "duration": 2.79}, {"text": "So just to remind you to\nbe explicit about this--", "start": 2496.42, "duration": 4.045}, {"text": "so.", "start": 2500.465, "duration": 0.5}, {"text": "So you have this flavin group\nattached to this ribitol group", "start": 2550.76, "duration": 5.29}, {"text": "with a phosphate on it.", "start": 2556.05, "duration": 1.5}, {"text": "If I put another phosphate and\nan adenine nucleotide here,", "start": 2557.55, "duration": 3.12}, {"text": "an AMP group attached\nhere, that would be FAD.", "start": 2560.67, "duration": 3.48}, {"text": "This would be FMN, nucleotide\ninstead of a dinucleotide.", "start": 2564.15, "duration": 4.89}, {"text": "This is FMN in\nthe oxidized form.", "start": 2569.04, "duration": 6.42}, {"text": "And just like FAD, it can\naccept an electron pair.", "start": 2575.46, "duration": 8.07}, {"text": "So here's our hydride\nion, two electrons", "start": 2583.53, "duration": 5.145}, {"text": "if we just draw here the\nmiddle part of the molecule.", "start": 2588.675, "duration": 3.505}, {"text": "And so this here would be\nFMNH2 or the reduced form", "start": 2600.87, "duration": 16.54}, {"text": "of this electron carrier, OK?", "start": 2617.41, "duration": 5.03}, {"text": "So flavin mononucleotide--\npart of the electron transport", "start": 2622.44, "duration": 4.88}, {"text": "chain.", "start": 2627.32, "duration": 0.94}, {"text": "Now, note FMN, FAD,\nNAD, all of these things", "start": 2628.26, "duration": 4.43}, {"text": "are two electron\ncarriers, right?", "start": 2632.69, "duration": 2.43}, {"text": "We disguise the\nmechanism of all of them,", "start": 2635.12, "duration": 2.7}, {"text": "just reminded you of\nit, these hydride ion", "start": 2637.82, "duration": 2.4}, {"text": "transfers, two\nelectron carriers.", "start": 2640.22, "duration": 2.56}, {"text": "It turns out the electron\ntransport chain also", "start": 2642.78, "duration": 3.14}, {"text": "uses metal ions as\nelectron carriers.", "start": 2645.92, "duration": 3.21}, {"text": "And so-- lots of minerals in\nour diet, things like iron.", "start": 2649.13, "duration": 3.69}, {"text": "It turns out elemental iron\nis a great electron carrier.", "start": 2652.82, "duration": 3.42}, {"text": "And it's very important for\nelectron transport chain.", "start": 2656.24, "duration": 5.08}, {"text": "Now, elemental metals\nare one electron carrier.", "start": 2661.32, "duration": 5.45}, {"text": "And so there's a few ways\nyou incorporate iron.", "start": 2666.77, "duration": 3.72}, {"text": "One is something called\niron sulfur clusters.", "start": 2670.49, "duration": 3.45}, {"text": "And so iron sulfur clusters\nis, within a protein,", "start": 2673.94, "duration": 4.17}, {"text": "you have some cysteine residues.", "start": 2678.11, "duration": 2.47}, {"text": "And those cysteine residues\ncan coordinate an iron atom.", "start": 2683.1, "duration": 6.07}, {"text": "And so that iron atom can sit\nin the 3+ versus 2+ state,", "start": 2689.17, "duration": 8.24}, {"text": "oxidized, reduced.", "start": 2697.41, "duration": 1.335}, {"text": "So reduction of the iron--", "start": 2702.86, "duration": 1.92}, {"text": "oxidation of the iron, OK?", "start": 2704.78, "duration": 3.0}, {"text": "So one electron carrier--", "start": 2707.78, "duration": 1.86}, {"text": "move one electron that way.", "start": 2709.64, "duration": 2.1}, {"text": "Also, ion sits within\nmolecules called cytochromes.", "start": 2711.74, "duration": 7.35}, {"text": "So what are cytochromes?", "start": 2719.09, "duration": 1.98}, {"text": "This is an iron atom\nthat's basically", "start": 2721.07, "duration": 3.87}, {"text": "chelated into a porphyrin\nvery similar to what", "start": 2724.94, "duration": 3.54}, {"text": "you saw for hemoglobin.", "start": 2728.48, "duration": 2.05}, {"text": "And so you have an iron 2+ or 3+\nthat's chelated here into this", "start": 2730.53, "duration": 24.34}, {"text": "porphyrin ring structure.", "start": 2754.87, "duration": 2.27}, {"text": "OK.", "start": 2769.05, "duration": 0.99}, {"text": "Lots of conjugated double\nbond systems in it,", "start": 2770.04, "duration": 2.52}, {"text": "this should look very similar.", "start": 2772.56, "duration": 1.85}, {"text": "Porphyrin is the thing on\nthe outside, coordinates iron", "start": 2774.41, "duration": 2.53}, {"text": "atom in the middle.", "start": 2776.94, "duration": 1.08}, {"text": "That can move between the 2+\nand the 3+ state just like we do", "start": 2778.02, "duration": 2.88}, {"text": "for iron sulfur clusters, so\ncarry electrons be oxidized", "start": 2780.9, "duration": 3.42}, {"text": "or reduced, 3+ or 2+.", "start": 2784.32, "duration": 2.79}, {"text": "And ultimately,\nthis porphyrin can", "start": 2787.11, "duration": 5.64}, {"text": "have some R groups added here,\ncan be associated with it", "start": 2792.75, "duration": 8.18}, {"text": "or bound to cysteine\nresidues within proteins.", "start": 2800.93, "duration": 3.63}, {"text": "Effectively, these molecules\nvarying these R groups", "start": 2804.56, "duration": 4.92}, {"text": "and how it's\nattached to proteins", "start": 2809.48, "duration": 2.49}, {"text": "gives you different families\nof cytochrome is referred", "start": 2811.97, "duration": 4.05}, {"text": "to as cytochrome A, the B type\ncytochromes, and cytochrome C.", "start": 2816.02, "duration": 8.7}, {"text": "These are associated\nwith enzyme complexes,", "start": 2824.72, "duration": 3.0}, {"text": "cytochrome C. It's\nactually covalently bound", "start": 2827.72, "duration": 2.37}, {"text": "to the polypeptide itself.", "start": 2830.09, "duration": 3.54}, {"text": "Basically, these are\nnamed because you", "start": 2833.63, "duration": 2.16}, {"text": "have these different conjugated\nring structures here.", "start": 2835.79, "duration": 5.77}, {"text": "That and how the R groups\nare will slightly change.", "start": 2841.56, "duration": 3.21}, {"text": "So this will absorb\nvisible light.", "start": 2844.77, "duration": 1.53}, {"text": "That will slightly change\nthe absorption spectra.", "start": 2846.3, "duration": 3.34}, {"text": "And so classically, based\non absorption spectra,", "start": 2849.64, "duration": 2.48}, {"text": "these were classified into\nA, B, and C type cytochromes.", "start": 2852.12, "duration": 3.69}, {"text": "And you can imagine,\nby these properties", "start": 2855.81, "duration": 2.04}, {"text": "having slightly different--", "start": 2857.85, "duration": 2.79}, {"text": "affecting the iron in\nways that it slightly", "start": 2860.64, "duration": 2.01}, {"text": "affects its electron\ntransport properties.", "start": 2862.65, "duration": 2.97}, {"text": "Of course, hemoglobin\nalmost certainly", "start": 2865.62, "duration": 2.82}, {"text": "evolved from these molecules\nas oxygen carrying ways", "start": 2868.44, "duration": 4.11}, {"text": "in multicellular life.", "start": 2872.55, "duration": 1.8}, {"text": "But of course, the original\nuse was as electron carriers", "start": 2874.35, "duration": 3.845}, {"text": "for the processes\nhere that we're", "start": 2878.195, "duration": 1.375}, {"text": "going to talk about, to\nhold that iron as a way", "start": 2879.57, "duration": 2.13}, {"text": "to control electron transport\nacross these electron transport", "start": 2881.7, "duration": 4.47}, {"text": "chains.", "start": 2886.17, "duration": 1.53}, {"text": "All right, so that's iron.", "start": 2887.7, "duration": 1.11}, {"text": "It turns out iron is\nnot the only metal that", "start": 2888.81, "duration": 3.03}, {"text": "can be used to do this.", "start": 2891.84, "duration": 1.69}, {"text": "And so cells also use copper.", "start": 2893.53, "duration": 3.11}, {"text": "And so histidine can coordinate\na copper that can move between", "start": 2896.64, "duration": 15.76}, {"text": "an oxidized and reduced state,\nso copper 2+ reduced to copper", "start": 2912.4, "duration": 3.81}, {"text": "+, copper + to copper 2+ or\ncopper + oxidized to copper 2+,", "start": 2916.21, "duration": 5.28}, {"text": "another one electron carrier.", "start": 2921.49, "duration": 2.76}, {"text": "And so iron and copper can\nact as one electron carriers.", "start": 2924.25, "duration": 4.887}, {"text": "And so you have these\ntwo electron carriers.", "start": 2929.137, "duration": 1.833}, {"text": "Here's a bunch of metals\nas one electron carriers.", "start": 2930.97, "duration": 2.67}, {"text": "Obviously, you need ways\nto carry both one and two", "start": 2933.64, "duration": 4.235}, {"text": "electrons if you're\ngoing to move", "start": 2937.875, "duration": 1.375}, {"text": "electrons between these\ndifferent carriers.", "start": 2939.25, "duration": 2.94}, {"text": "And an important molecule\nto do that is something", "start": 2942.19, "duration": 3.51}, {"text": "called coenzyme Q. Coenzyme Q--", "start": 2945.7, "duration": 6.46}, {"text": "sometimes referred to\nas ubiquinone ubiquinol,", "start": 2952.16, "duration": 9.87}, {"text": "because it's ubiquitous, often\nabbreviated co-Q. Many of you", "start": 2962.03, "duration": 7.168}, {"text": "have probably heard\nof the supplement", "start": 2969.198, "duration": 1.542}, {"text": "CoQ10, very popular\nsupplement out there.", "start": 2970.74, "duration": 4.17}, {"text": "CoQ10 is basically a\nversion of coenzyme Q,", "start": 2974.91, "duration": 3.93}, {"text": "ubiquinone, ubiquinol.", "start": 2978.84, "duration": 2.13}, {"text": "What this looks\nlike is as follows.", "start": 2980.97, "duration": 1.65}, {"text": "So this here is ubiquinone,\nthe oxidized form.", "start": 3003.75, "duration": 8.72}, {"text": "So this middle part\nis the quinone.", "start": 3012.47, "duration": 3.39}, {"text": "And then you have these\ndecorations on the outside,", "start": 3015.86, "duration": 2.85}, {"text": "including this R group.", "start": 3018.71, "duration": 1.53}, {"text": "This R group is typically\na long acyl tail.", "start": 3020.24, "duration": 3.15}, {"text": "If it's 10 carbons long,\nthat's CoQ10 supplement.", "start": 3023.39, "duration": 4.14}, {"text": "Having this long\nacyl chain makes this", "start": 3027.53, "duration": 2.28}, {"text": "a very hydrophobic molecule.", "start": 3029.81, "duration": 1.71}, {"text": "And it actually lives\nwithin the membrane itself", "start": 3031.52, "duration": 4.02}, {"text": "as an electron carrier.", "start": 3035.54, "duration": 1.77}, {"text": "And so this ubiquinone can\npick up an electron as well as", "start": 3037.31, "duration": 8.645}, {"text": "a proton.", "start": 3045.955, "duration": 0.5}, {"text": "Whoops.", "start": 3049.192, "duration": 0.5}, {"text": "And so by picking\nup one electron,", "start": 3057.49, "duration": 6.79}, {"text": "it can then basically go here\nto this semiquinone stabilized", "start": 3064.28, "duration": 20.83}, {"text": "free radical state\nand then pick up", "start": 3085.11, "duration": 2.46}, {"text": "a second electron to go\nto the fully reduced form.", "start": 3087.57, "duration": 6.965}, {"text": "ubiquinol.", "start": 3105.55, "duration": 0.63}, {"text": "OK.", "start": 3111.18, "duration": 0.9}, {"text": "So one electronic carrier\nand two electron carrier--", "start": 3112.08, "duration": 3.72}, {"text": "so basically, it can\ncarry two electrons", "start": 3115.8, "duration": 4.05}, {"text": "from the oxidized,\nthe reduced form,", "start": 3119.85, "duration": 1.86}, {"text": "but can transfer them\nas single electrons", "start": 3121.71, "duration": 3.3}, {"text": "by going through this stabilized\nfree radical ubiquinone state.", "start": 3125.01, "duration": 6.24}, {"text": "And so, basically, these\nvarious electron carriers", "start": 3131.25, "duration": 3.15}, {"text": "are associated with\nthese protein complexes", "start": 3134.4, "duration": 4.41}, {"text": "within this electron transport\nchain that ultimately works", "start": 3138.81, "duration": 3.93}, {"text": "to couple favorable\nelectron transport down", "start": 3142.74, "duration": 3.6}, {"text": "the chain to pumping protons\nto generate this potential", "start": 3146.34, "duration": 4.32}, {"text": "across the membrane.", "start": 3150.66, "duration": 2.67}, {"text": "All right, so this\nprocess occurs, again,", "start": 3153.33, "duration": 14.59}, {"text": "at the bacterial membrane or\nthe inner mitochondrial membrane", "start": 3167.92, "duration": 3.93}, {"text": "and, in animals\nand most organisms,", "start": 3171.85, "duration": 9.49}, {"text": "operates with four large\nmulti-subunit protein", "start": 3181.34, "duration": 9.15}, {"text": "complexes, all right?", "start": 3190.49, "duration": 2.85}, {"text": "Each of these protein complexes\nhas multiple polypeptides,", "start": 3193.34, "duration": 6.6}, {"text": "as I said.", "start": 3199.94, "duration": 0.5}, {"text": "It's coming together to form\nthese complexes just like we", "start": 3200.44, "duration": 2.47}, {"text": "described for pH, for instance.", "start": 3202.91, "duration": 2.49}, {"text": "Most of the\ncomponents of this are", "start": 3205.4, "duration": 2.28}, {"text": "encoded in the nuclear\ngenome, but a subset of these", "start": 3207.68, "duration": 3.48}, {"text": "are encoded in the\nmitochondrial genome.", "start": 3211.16, "duration": 2.34}, {"text": "Now, what exactly is encoded in\ndifferent mitochondrial genomes", "start": 3213.5, "duration": 3.18}, {"text": "varies by organisms.", "start": 3216.68, "duration": 2.01}, {"text": "But across organisms,\nit's basically", "start": 3218.69, "duration": 3.27}, {"text": "mostly complex components\nof these protein complexes.", "start": 3221.96, "duration": 5.25}, {"text": "And so this is why\nmitochondrial DNA is retained.", "start": 3227.21, "duration": 2.58}, {"text": "It's kind of this vestige of\nthis symbiotic relationship.", "start": 3229.79, "duration": 3.36}, {"text": "The mitochondria have\nretained some of the ability", "start": 3233.15, "duration": 2.88}, {"text": "to control their own\nenergy transduction, sort", "start": 3236.03, "duration": 3.495}, {"text": "of core components\nof these complexes.", "start": 3239.525, "duration": 2.985}, {"text": "There is one soluble protein.", "start": 3242.51, "duration": 3.51}, {"text": "So these complexes are\nembedded within the membrane.", "start": 3246.02, "duration": 3.39}, {"text": "There's also one\nsoluble protein that's", "start": 3249.41, "duration": 2.91}, {"text": "associated with the membrane.", "start": 3252.32, "duration": 1.71}, {"text": "And then there's\ncoenzyme Q, which also", "start": 3254.03, "duration": 5.16}, {"text": "floats within the membrane.", "start": 3259.19, "duration": 2.27}, {"text": "So that's in the membrane.", "start": 3261.46, "duration": 4.14}, {"text": "These are embedded\nin the membrane.", "start": 3265.6, "duration": 3.572}, {"text": "And then there's a\nsoluble protein that's", "start": 3269.172, "duration": 1.708}, {"text": "associated with the membrane.", "start": 3270.88, "duration": 1.53}, {"text": "OK, now I want to discuss the\ndetails of what these protein", "start": 3311.39, "duration": 4.26}, {"text": "complexes are and also few\ncomments about how they work.", "start": 3315.65, "duration": 8.14}, {"text": "So if this is the\ninner membrane space", "start": 3323.79, "duration": 2.36}, {"text": "and this is the\nmatrix side, that'd", "start": 3326.15, "duration": 2.01}, {"text": "be out or in if we're\ndiscussing a prokaryote.", "start": 3328.16, "duration": 6.3}, {"text": "The first is we have something\ncalled complex I, also", "start": 3334.46, "duration": 18.8}, {"text": "referred to as NADH oxidase\nbecause it oxidizes NADH back", "start": 3353.26, "duration": 13.335}, {"text": "to NAD.", "start": 3366.595, "duration": 0.5}, {"text": "NADH oxidase is a giant complex\ngreater than 900 kilodaltons", "start": 3371.53, "duration": 8.49}, {"text": "in total.", "start": 3380.02, "duration": 1.095}, {"text": "It has more than 25\nindividual protein subunits,", "start": 3381.115, "duration": 10.115}, {"text": "contains some flavin\nmononucleotides as well as", "start": 3391.23, "duration": 6.18}, {"text": "some iron sulfur clusters\nas electron carriers.", "start": 3397.41, "duration": 5.34}, {"text": "And it is the least\nwell-understood", "start": 3402.75, "duration": 4.62}, {"text": "of all of the protein complexes.", "start": 3407.37, "duration": 1.68}, {"text": "In fact, it is still\na major field of study", "start": 3409.05, "duration": 4.47}, {"text": "to try to understand how\nNAD oxidase really works.", "start": 3413.52, "duration": 4.41}, {"text": "But it effectively is one of the\ncomplexes that can pump protons", "start": 3417.93, "duration": 5.19}, {"text": "across the membrane as those\ntwo electrons are transferred", "start": 3423.12, "duration": 4.65}, {"text": "through the complex from NADH\nultimately to coenzyme Q that", "start": 3427.77, "duration": 9.3}, {"text": "exists within the membrane.", "start": 3437.07, "duration": 3.65}, {"text": "OK, the next complex\ndiscuss is complex II.", "start": 3440.72, "duration": 13.29}, {"text": "Complex II is succinate\ndehydrogenase, the exact enzyme", "start": 3454.01, "duration": 10.43}, {"text": "that we heard about\nfrom the TCA cycle.", "start": 3464.44, "duration": 3.39}, {"text": "So what does succinate\ndehydrogenase do?", "start": 3467.83, "duration": 3.69}, {"text": "Remember, it converts\nfumarate to succinate.", "start": 3471.52, "duration": 3.24}, {"text": "It gave those electrons\nto FAD to make FADH2.", "start": 3474.76, "duration": 9.44}, {"text": "Well, that occurs\nwithin this complex,", "start": 3484.2, "duration": 3.22}, {"text": "which can also reoxidize the\nFADH2 with those two electrons", "start": 3487.42, "duration": 6.59}, {"text": "and give them,\nalso, to coenzyme Q", "start": 3494.01, "duration": 4.53}, {"text": "that sits within the membrane.", "start": 3498.54, "duration": 3.25}, {"text": "So I want to point out that\nthis, ultimately, you will see,", "start": 3501.79, "duration": 6.02}, {"text": "is why it is that electron\ntransfer from NADH and FADH2", "start": 3507.81, "duration": 6.72}, {"text": "has different energy yields.", "start": 3514.53, "duration": 3.27}, {"text": "And so the electron transfer\nfrom NADH to ubiquinone", "start": 3517.8, "duration": 6.45}, {"text": "is more of a change in\nstandard reduction potential", "start": 3524.25, "duration": 3.78}, {"text": "than from FADH2 to ubiquinone.", "start": 3528.03, "duration": 3.42}, {"text": "Why use FADH2?", "start": 3531.45, "duration": 2.01}, {"text": "Well, because, remember when\nwe did electron transfers,", "start": 3533.46, "duration": 3.57}, {"text": "we used, when we\noxidized a carbon, say,", "start": 3537.03, "duration": 8.34}, {"text": "in a carbohydrate to a ketone,\nwe tended to use NAD+/NADH", "start": 3545.37, "duration": 9.99}, {"text": "as the electron transport pair.", "start": 3555.36, "duration": 3.63}, {"text": "So this change in\nstandard reduction", "start": 3558.99, "duration": 2.25}, {"text": "potential is such that we\ncan make that reaction work", "start": 3561.24, "duration": 4.92}, {"text": "and ultimately drive that.", "start": 3566.16, "duration": 1.98}, {"text": "It turns out that putting\na double bond in--", "start": 3568.14, "duration": 6.18}, {"text": "this going from a not oxidizing\nan alcohol to a ketone,", "start": 3574.32, "duration": 6.09}, {"text": "but oxidizing the carbon\nto a double bond--", "start": 3580.41, "duration": 2.97}, {"text": "that basically you\nneed a different change", "start": 3583.38, "duration": 7.13}, {"text": "in standard reduction potential\nto carry out that reaction", "start": 3590.51, "duration": 4.53}, {"text": "and make it work.", "start": 3595.04, "duration": 2.1}, {"text": "FADH/FADH2 sits at a\nhigher standard reduction", "start": 3597.14, "duration": 4.53}, {"text": "potential than NAD/NADH.", "start": 3601.67, "duration": 2.91}, {"text": "And so that means to\nfurther transfer them", "start": 3604.58, "duration": 3.51}, {"text": "to something further\ndownstream, like coenzyme Q,", "start": 3608.09, "duration": 6.588}, {"text": "there's a bigger change in\nstandard reduction potential", "start": 3614.678, "duration": 2.292}, {"text": "here.", "start": 3616.97, "duration": 0.5}, {"text": "That can be used\nto drive protons.", "start": 3617.47, "duration": 1.66}, {"text": "There's not enough\nof a change here.", "start": 3619.13, "duration": 1.71}, {"text": "You can't use that\nto drive protons.", "start": 3620.84, "duration": 2.28}, {"text": "And it's because of\nthese differences", "start": 3623.12, "duration": 2.28}, {"text": "in what's actually being\noxidized that ultimately leads", "start": 3625.4, "duration": 3.96}, {"text": "to this difference in energetics\nwhen we think about FADH2", "start": 3629.36, "duration": 6.39}, {"text": "versus NADH and how\nmuch ATP equivalence", "start": 3635.75, "duration": 4.05}, {"text": "that they might have for cells.", "start": 3639.8, "duration": 2.48}, {"text": "All right, once electrons\nare in the ubiquinone pool", "start": 3642.28, "duration": 7.57}, {"text": "or coenzyme Q pool, they can now\nbe transferred to complex III.", "start": 3649.85, "duration": 8.13}, {"text": "So complex III is also referred\nto as cytochrome C reductase.", "start": 3657.98, "duration": 13.86}, {"text": "You'll see why in a second.", "start": 3671.84, "duration": 2.4}, {"text": "It's a 250 kilodalton complex.", "start": 3674.24, "duration": 5.67}, {"text": "There are 10 subunits.", "start": 3679.91, "duration": 3.9}, {"text": "It has a bunch of B type\nand C type cytochromes,", "start": 3683.81, "duration": 11.91}, {"text": "as well as some iron\nsulfur clusters.", "start": 3695.72, "duration": 5.17}, {"text": "Shown here on the\nslide from a textbook", "start": 3700.89, "duration": 2.7}, {"text": "is a picture of complex III and\nwhat it actually looks like.", "start": 3703.59, "duration": 7.14}, {"text": "Fairly well-understood\nhow it works,", "start": 3710.73, "duration": 3.6}, {"text": "this coupling of basically\nelectron transfer through the Q", "start": 3714.33, "duration": 4.11}, {"text": "pool can pump protons.", "start": 3718.44, "duration": 2.385}, {"text": "And this ultimately\nallows transfer", "start": 3724.47, "duration": 4.47}, {"text": "of electrons to this\nsmall soluble protein that", "start": 3728.94, "duration": 6.12}, {"text": "lives in the intermembrane space\nor associated with the outside", "start": 3735.06, "duration": 3.54}, {"text": "of the bacteria\ncalled cytochrome C--", "start": 3738.6, "duration": 3.45}, {"text": "or outside in the intermembrane\nspace called cytochrome C.", "start": 3742.05, "duration": 3.6}, {"text": "Cytochrome C is a 13\nkilodalton protein.", "start": 3745.65, "duration": 9.19}, {"text": "It's a very small\nhighly conserved protein", "start": 3754.84, "duration": 3.68}, {"text": "with a C type\ncytochrome commonly used", "start": 3758.52, "duration": 2.753}, {"text": "because it's found across\nmany, many different types", "start": 3761.273, "duration": 2.167}, {"text": "of organisms.", "start": 3763.44, "duration": 0.73}, {"text": "And so it's been sequenced\nfrom many, many organisms", "start": 3764.17, "duration": 3.26}, {"text": "as a way to identify\nevolutionary relationships.", "start": 3767.43, "duration": 3.12}, {"text": "And then cytochrome\nC, this is also", "start": 3770.55, "duration": 2.04}, {"text": "why it's called cytochrome\nC reductase because it's", "start": 3772.59, "duration": 2.82}, {"text": "reducing cytochrome C\nto transfer electrons", "start": 3775.41, "duration": 4.23}, {"text": "along the chain, ultimately to\nthe final complex, complex IV.", "start": 3779.64, "duration": 7.56}, {"text": "Complex IV-- also referred\nto as cytochrome C oxidase.", "start": 3787.2, "duration": 7.38}, {"text": "And this is ultimately the place\nwhere electrons are transferred", "start": 3794.58, "duration": 6.21}, {"text": "to reduce oxygen to water.", "start": 3800.79, "duration": 3.91}, {"text": "So this is 160 kilodalton\nprotein complex", "start": 3804.7, "duration": 5.6}, {"text": "with 13 subunits, uses A\ntype cytochromes and copper", "start": 3810.3, "duration": 15.67}, {"text": "as electron carriers\nand, ultimately,", "start": 3825.97, "duration": 4.74}, {"text": "allows you to get electrons\nfrom cytochrome C to oxygen.", "start": 3830.71, "duration": 4.44}, {"text": "And so here, again,\nfrom the textbook", "start": 3835.15, "duration": 2.19}, {"text": "is a picture of complex\nIV and what it looks like.", "start": 3837.34, "duration": 5.85}, {"text": "Also, fairly well-understood--\nalso couples electron transport", "start": 3843.19, "duration": 5.4}, {"text": "to proton pumping.", "start": 3848.59, "duration": 3.55}, {"text": "And so this is effectively\nthe electron transport chain", "start": 3852.14, "duration": 5.91}, {"text": "as it exists in mitochondria.", "start": 3858.05, "duration": 1.95}, {"text": "And you can draw it a different\nway as I will do here.", "start": 3860.0, "duration": 5.65}, {"text": "So here's complex I, allows\noxidation of NADH back to NAD+.", "start": 3865.65, "duration": 10.06}, {"text": "That oxidation can be\ncoupled to reduction of FMN.", "start": 3880.89, "duration": 7.59}, {"text": "Ultimately, those are passed\nthrough some iron sulfur", "start": 3888.48, "duration": 15.02}, {"text": "clusters leading to the\nreduction of ubiquinone.", "start": 3903.5, "duration": 9.12}, {"text": "And in the process,\nthis electron transport", "start": 3912.62, "duration": 5.04}, {"text": "can pump on the order\nof four protons,", "start": 3917.66, "duration": 3.06}, {"text": "or at least that's\nwhat's estimated.", "start": 3920.72, "duration": 2.43}, {"text": "Complex II, which is succinate\ndehydrogenase from the TCA", "start": 3923.15, "duration": 6.36}, {"text": "cycle, really converts\nsuccinate to fumarate.", "start": 3929.51, "duration": 8.39}, {"text": "That oxidation reaction\nwithin the complex", "start": 3937.9, "duration": 7.08}, {"text": "leads to the reduction\nof FAD to FADH2.", "start": 3944.98, "duration": 5.62}, {"text": "That can be reoxidized\nthrough iron,", "start": 3950.6, "duration": 9.57}, {"text": "ultimately driving the\nreduction of coenzyme Q", "start": 3960.17, "duration": 8.54}, {"text": "from ubiquinone to ubiquinol.", "start": 3968.71, "duration": 2.73}, {"text": "That ubiquinone to you\nubiquinol in something", "start": 3971.44, "duration": 4.32}, {"text": "called the Q pool\nwithin the membrane", "start": 3975.76, "duration": 4.2}, {"text": "can then be reoxidized\nin complex III.", "start": 3979.96, "duration": 12.35}, {"text": "That reoxidized in\ncomplex III puts electrons", "start": 3992.31, "duration": 6.36}, {"text": "through complex III that\ncan be coupled to pumping", "start": 3998.67, "duration": 3.9}, {"text": "on the order of two protons.", "start": 4002.57, "duration": 3.36}, {"text": "Those electrons are transferred\nto cytochrome C. Ultimately,", "start": 4005.93, "duration": 6.09}, {"text": "those electrons are transferred\nto copper in complex IV", "start": 4012.02, "duration": 8.78}, {"text": "to cytochrome A and,\nultimately, oxygen to water,", "start": 4020.8, "duration": 8.04}, {"text": "reducing oxygen to\nwater and pumping", "start": 4028.84, "duration": 3.23}, {"text": "on the order of four protons.", "start": 4032.07, "duration": 4.2}, {"text": "And so you can see here\nthat, basically, this", "start": 4036.27, "duration": 6.12}, {"text": "is a series of oxidation\nand reduction reactions", "start": 4042.39, "duration": 4.53}, {"text": "that happens across these\ncomplexes, such that complex I,", "start": 4046.92, "duration": 5.34}, {"text": "the transfer electrons from\nthe Q pool through complex III.", "start": 4052.26, "duration": 2.91}, {"text": "And complex IV can pump\nprotons across the membrane", "start": 4055.17, "duration": 4.83}, {"text": "and generate this\ndelta psi delta", "start": 4060.0, "duration": 2.4}, {"text": "pH that can be used to do work.", "start": 4062.4, "duration": 2.58}, {"text": "And it's really the favorable\ntransfer of electrons", "start": 4064.98, "duration": 2.7}, {"text": "either from NAD/NADH or the\noxidation of the succinate", "start": 4067.68, "duration": 3.9}, {"text": "to fumarate with those electrons\nbeing given to oxygen to drive", "start": 4071.58, "duration": 4.62}, {"text": "this process.", "start": 4076.2, "duration": 2.26}, {"text": "And so really just to schematize\nthis, in a way, is that,", "start": 4078.46, "duration": 9.58}, {"text": "if this is our membrane, NAD+ to\nNADH gives electrons to complex", "start": 4088.04, "duration": 11.04}, {"text": "I, which goes to coenzyme Q,\nwhich goes to complex III,", "start": 4099.08, "duration": 5.58}, {"text": "which goes to cytochrome\nC, which goes to complex IV", "start": 4104.66, "duration": 4.17}, {"text": "and reduces oxygen to water.", "start": 4108.83, "duration": 5.489}, {"text": "That is one way to carry\nout this set of reactions.", "start": 4114.319, "duration": 3.931}, {"text": "The other way is we\ncan convert fumarate--", "start": 4118.25, "duration": 5.045}, {"text": "sorry, succinate to fumarate.", "start": 4123.295, "duration": 5.335}, {"text": "That's the FAD.", "start": 4128.63, "duration": 1.89}, {"text": "That's complex II, also\ngives it to the Q pool.", "start": 4130.52, "duration": 3.87}, {"text": "And so you can see that\nthe electron transport", "start": 4134.39, "duration": 2.4}, {"text": "chain would be complex I, Q,\nIII C, IV or II Q, III, C IV.", "start": 4136.79, "duration": 6.0}, {"text": "It is not I, II, III, IV.", "start": 4142.79, "duration": 2.37}, {"text": "It is actually I to Q or II\nto Q, ultimately going to III.", "start": 4145.16, "duration": 6.606}, {"text": "Now, the way protons\nare pumped is a process", "start": 4151.766, "duration": 4.104}, {"text": "that I don't have time this\nyear to discuss in class.", "start": 4155.87, "duration": 3.42}, {"text": "I will post something\non Stellar that is just", "start": 4159.29, "duration": 2.52}, {"text": "a short section from the\ntextbook that describes", "start": 4161.81, "duration": 3.18}, {"text": "at least what is known about\nhow that process works,", "start": 4164.99, "duration": 3.869}, {"text": "such as the Q cycle,\nbasically how oxidation", "start": 4168.859, "duration": 4.141}, {"text": "and reduction of coenzyme\nQ, which will take protons", "start": 4173.0, "duration": 4.05}, {"text": "on and off the molecule on\neither side of the membrane,", "start": 4177.05, "duration": 2.61}, {"text": "can be used to show how this\ncan be coupled to proton", "start": 4179.66, "duration": 4.68}, {"text": "pumping across the membrane.", "start": 4184.34, "duration": 2.86}, {"text": "And you can read that\nif you're interested.", "start": 4187.2, "duration": 3.97}, {"text": "OK.", "start": 4191.17, "duration": 1.59}, {"text": "Now, a couple other\npoints about this, this", "start": 4192.76, "duration": 6.13}, {"text": "works because you're\nmoving from a lower", "start": 4198.89, "duration": 6.56}, {"text": "to a higher standard reduction\npotential across the chain.", "start": 4205.45, "duration": 3.36}, {"text": "And it turns out oxygen is\na particularly good electron", "start": 4208.81, "duration": 4.53}, {"text": "acceptor.", "start": 4213.34, "duration": 1.2}, {"text": "And this is really why oxygen\nand respiration is really", "start": 4214.54, "duration": 3.78}, {"text": "so vital to a lot of the\nway energy transduction", "start": 4218.32, "duration": 3.96}, {"text": "works in metabolism.", "start": 4222.28, "duration": 1.86}, {"text": "Oxygen is now abundant.", "start": 4224.14, "duration": 1.62}, {"text": "And being a great electron\nacceptor is why it's used.", "start": 4225.76, "duration": 2.5}, {"text": "But of course, oxygen\nwas not abundant", "start": 4228.26, "duration": 1.94}, {"text": "2 and 1/2 billion years ago.", "start": 4230.2, "duration": 2.4}, {"text": "And it doesn't have to be\noxygen for this to work.", "start": 4232.6, "duration": 4.6}, {"text": "If you have another\nelectron acceptor that", "start": 4237.2, "duration": 3.02}, {"text": "basically makes this\nprocess favorable,", "start": 4240.22, "duration": 2.76}, {"text": "that can work just as well.", "start": 4242.98, "duration": 1.54}, {"text": "And in fact, that happens\nstill in some very extreme", "start": 4244.52, "duration": 3.98}, {"text": "environments.", "start": 4248.5, "duration": 1.17}, {"text": "This so-called\nchemosynthesis basically", "start": 4249.67, "duration": 2.94}, {"text": "can use other\nelectronic acceptors", "start": 4252.61, "duration": 3.6}, {"text": "to drive the\nenergetics of cells.", "start": 4256.21, "duration": 3.09}, {"text": "And you really just\nneed the right ways", "start": 4259.3, "duration": 4.76}, {"text": "to build an electron transport\nchain to make this whole system", "start": 4264.06, "duration": 3.66}, {"text": "work, such you can build a\nbattery and use it to do work,", "start": 4267.72, "duration": 3.43}, {"text": "OK?", "start": 4271.15, "duration": 0.5}, {"text": "So oxygen-- commonly used\nbecause it's abundant and good", "start": 4271.65, "duration": 3.42}, {"text": "at it, but it's not the\nonly way that this can work.", "start": 4275.07, "duration": 3.18}, {"text": "And there are\nexamples in biology", "start": 4278.25, "duration": 1.56}, {"text": "where oxygen is not used, that\nthere is other acceptors that", "start": 4279.81, "duration": 4.02}, {"text": "are used instead.", "start": 4283.83, "duration": 2.15}, {"text": "Now, I also want to note, as\nI've alluded to in discussing", "start": 4285.98, "duration": 3.45}, {"text": "complex II, this FAD/FADH2.", "start": 4289.43, "duration": 4.14}, {"text": "So when we talk about\nthat in the TCA cycle", "start": 4293.57, "duration": 3.69}, {"text": "or in fatty acid\noxidation, we discuss it", "start": 4297.26, "duration": 3.09}, {"text": "as if it's kind of like\nNAD/NADH, but it's not.", "start": 4300.35, "duration": 3.69}, {"text": "NAD/NADH are basically\ncofactors that", "start": 4304.04, "duration": 4.29}, {"text": "move around between enzymes.", "start": 4308.33, "duration": 1.77}, {"text": "Fad/fadh2 are not free.", "start": 4310.1, "duration": 4.83}, {"text": "They're electron carriers that\nare part of protein complexes,", "start": 4314.93, "duration": 4.56}, {"text": "like what we described up here.", "start": 4319.49, "duration": 3.51}, {"text": "And they're part of enzymes\nlike succinate dehydrogenase.", "start": 4323.0, "duration": 2.97}, {"text": "So complex II just happens to be\nan FAD/FADH2 containing enzyme", "start": 4325.97, "duration": 7.2}, {"text": "that's part of the TCA cycle and\npart of the electron transport", "start": 4333.17, "duration": 3.81}, {"text": "chain as a way to transfer\nelectrons in the TCA cycle", "start": 4336.98, "duration": 3.9}, {"text": "into the Q pool\nvia this succinate", "start": 4340.88, "duration": 3.91}, {"text": "to fumarate conversion.", "start": 4344.79, "duration": 2.21}, {"text": "Acyl-CoA dehydrogenase,\nthe FAD/FADH2 enzyme", "start": 4347.0, "duration": 3.66}, {"text": "we discussed in\nfatty acid oxidation,", "start": 4350.66, "duration": 2.37}, {"text": "could easily be drawn instead\nin electron transport chain that", "start": 4353.03, "duration": 3.99}, {"text": "goes acyl-CoA dehydrogenase,\ncoenzyme Q, III, C, IV,", "start": 4357.02, "duration": 4.83}, {"text": "just like we can say\nsuccinate to fumarate", "start": 4361.85, "duration": 2.01}, {"text": "is the same as complex\nII, Q, III, C, IV, OK?", "start": 4363.86, "duration": 4.02}, {"text": "And so there's really lots of\nalternative electron transport", "start": 4367.88, "duration": 3.66}, {"text": "chains that involve these\nFAD/FADH2 containing enzymes", "start": 4371.54, "duration": 4.29}, {"text": "that really sit in the membrane\nand directly transfer electrons", "start": 4375.83, "duration": 4.02}, {"text": "to the Q pool.", "start": 4379.85, "duration": 3.93}, {"text": "Ultimately, the\ngoal of all of this", "start": 4383.78, "duration": 2.64}, {"text": "is, of course, to create\nthis delta psi delta", "start": 4386.42, "duration": 3.84}, {"text": "pH, which can be used to charge\nthis battery that then can then", "start": 4390.26, "duration": 4.53}, {"text": "be done to do work.", "start": 4394.79, "duration": 2.05}, {"text": "And so this work includes\nthe phosphorylation of ATP.", "start": 4396.84, "duration": 5.27}, {"text": "And so if we charge\nthis battery,", "start": 4402.11, "duration": 3.09}, {"text": "we can now use this as a way to\ncouple current in this battery", "start": 4405.2, "duration": 11.05}, {"text": "to phosphorylate ADP to make\nATP, the phosphorylation part", "start": 4416.25, "duration": 5.43}, {"text": "of oxidative phosphorylation.", "start": 4421.68, "duration": 3.15}, {"text": "Now, this occurs also by a\nlarge protein complex sometimes", "start": 4424.83, "duration": 3.9}, {"text": "referred to as complex\nV. But remember,", "start": 4428.73, "duration": 3.48}, {"text": "complex V, or this ATP\nsynthase machinery,", "start": 4432.21, "duration": 3.48}, {"text": "is not really part of the\nelectron transport chain.", "start": 4435.69, "duration": 3.03}, {"text": "It is separate in space and\nis basically something, a way,", "start": 4438.72, "duration": 4.17}, {"text": "to utilize this delta psi\ndelta pH across the membrane", "start": 4442.89, "duration": 4.56}, {"text": "to drive ATP synthesis.", "start": 4447.45, "duration": 4.14}, {"text": "All right, how does this\ncomplex V or ATP synthesis work?", "start": 4451.59, "duration": 7.6}, {"text": "So this is also a\nlarge protein complex,", "start": 4462.37, "duration": 6.83}, {"text": "sits within the same\nmembrane, of course,", "start": 4469.2, "duration": 3.1}, {"text": "because it has to utilize the\nmembrane potential to function.", "start": 4472.3, "duration": 4.34}, {"text": "And the so-called\ncomplex V is also", "start": 4491.05, "duration": 7.88}, {"text": "referred to as the ATP\nsynthase or the F0 F1 ATPase.", "start": 4498.93, "duration": 13.82}, {"text": "And basically, if this is\nthe intermembrane space,", "start": 4512.75, "duration": 6.44}, {"text": "this is the inner\nmitochondrial membrane.", "start": 4519.19, "duration": 3.46}, {"text": "This is the matrix.", "start": 4522.65, "duration": 2.59}, {"text": "You have a protein\ncomplex that sits", "start": 4525.24, "duration": 4.12}, {"text": "within the membrane called F0.", "start": 4529.36, "duration": 4.23}, {"text": "It's actually FO.", "start": 4533.59, "duration": 1.83}, {"text": "The O stands for a\nOligomycin because there's", "start": 4535.42, "duration": 4.05}, {"text": "a drug called oligomycin\nthat inhibits the FO,", "start": 4539.47, "duration": 3.0}, {"text": "or F0, part of the molecule.", "start": 4542.47, "duration": 3.78}, {"text": "And then there's\nthis F1 component", "start": 4546.25, "duration": 3.45}, {"text": "that is associated with\nthe F0 component that", "start": 4549.7, "duration": 3.06}, {"text": "sits on the matrix\nside of the membrane.", "start": 4552.76, "duration": 2.19}, {"text": "And it is effectively\nthe machine", "start": 4554.95, "duration": 3.3}, {"text": "that phosphorylates\nor interconverts", "start": 4558.25, "duration": 6.58}, {"text": "ATP and ADP on the matrix\nside of the membrane.", "start": 4564.83, "duration": 6.25}, {"text": "Now, it's pretty well-understood\nhow this system works.", "start": 4571.08, "duration": 4.02}, {"text": "And basically, F1\nworks by a process", "start": 4575.1, "duration": 2.69}, {"text": "called rotational catalysis.", "start": 4577.79, "duration": 3.57}, {"text": "How this works was awarded\nthe Nobel Prize in 1997,", "start": 4581.36, "duration": 3.51}, {"text": "figured out not\nall that long ago.", "start": 4584.87, "duration": 3.06}, {"text": "And basically, this is F1 is\na large protein complex where", "start": 4587.93, "duration": 4.83}, {"text": "you have a gamma\nsubunit that is attached", "start": 4592.76, "duration": 3.72}, {"text": "to F0 the couples, basically,\nproton pumping to this gamma", "start": 4596.48, "duration": 5.04}, {"text": "subunit to literally\nturn the F1 component", "start": 4601.52, "duration": 5.34}, {"text": "and change the confirmation\nof attached regions, parts,", "start": 4606.86, "duration": 6.18}, {"text": "of this F1 machine.", "start": 4613.04, "duration": 2.79}, {"text": "Because it turns\nout you can have", "start": 4615.83, "duration": 1.44}, {"text": "three different conformations\nof the rest of F1,", "start": 4617.27, "duration": 3.78}, {"text": "the so-called L, or Loose,\nconformation, the T,", "start": 4621.05, "duration": 3.33}, {"text": "or Tight, conformation, or\nthe O, or Open, conformation.", "start": 4624.38, "duration": 5.1}, {"text": "And so in the open conformation,\nADP and phosphate or ATP", "start": 4629.48, "duration": 14.81}, {"text": "can exchange in and out of\nthis complex, all right?", "start": 4644.29, "duration": 6.59}, {"text": "In the loose confirmation,\nyou basically", "start": 4650.88, "duration": 3.84}, {"text": "have ADP and phosphate bound.", "start": 4654.72, "duration": 3.78}, {"text": "And in the tight\nconformation, this", "start": 4658.5, "duration": 5.13}, {"text": "is favored to synthesize ATP.", "start": 4663.63, "duration": 6.27}, {"text": "And so you can envision that\nwhat actually happens here", "start": 4669.9, "duration": 5.61}, {"text": "is that you first\nhave ADP and ATP", "start": 4675.51, "duration": 4.47}, {"text": "bind in this open conformation.", "start": 4679.98, "duration": 5.86}, {"text": "Protons are moved.", "start": 4690.82, "duration": 1.83}, {"text": "You get rotation around\nthe gamma subunit.", "start": 4692.65, "duration": 4.03}, {"text": "That changes the\nconformation of the O subunit", "start": 4696.68, "duration": 3.93}, {"text": "to the loose subunit.", "start": 4700.61, "duration": 1.35}, {"text": "So now, you have\nADP plus PI bound.", "start": 4701.96, "duration": 4.08}, {"text": "Another proton moves,\nchanges the conformation", "start": 4706.04, "duration": 4.83}, {"text": "of the loose subunit into\nthe tight confirmation.", "start": 4710.87, "duration": 5.16}, {"text": "Now, ATP synthase is favored.", "start": 4716.03, "duration": 4.77}, {"text": "Another proton moves, comes\nback to the open conformation.", "start": 4720.8, "duration": 6.12}, {"text": "ATP is released\nfrom the molecule,", "start": 4726.92, "duration": 2.7}, {"text": "and you can run another\nrotational catalysis cycle", "start": 4729.62, "duration": 3.3}, {"text": "again to ultimately drive\nATP to ATP synthase using", "start": 4732.92, "duration": 5.82}, {"text": "this transfer of protons\nacross the F0 subunit", "start": 4738.74, "duration": 5.01}, {"text": "to ultimately rotate this\nmachine to synthesize ATP.", "start": 4743.75, "duration": 6.41}, {"text": "Now, the way F0 works\nis within the membrane--", "start": 4750.16, "duration": 4.05}, {"text": "and this is always\nhard to draw--", "start": 4754.21, "duration": 3.93}, {"text": "you basically have\na central complex", "start": 4758.14, "duration": 13.98}, {"text": "with another set of\ncomplexes around it", "start": 4772.12, "duration": 2.58}, {"text": "that, within that, have\ntwo half-channels that", "start": 4774.7, "duration": 4.23}, {"text": "are open to either\nside of the membrane.", "start": 4778.93, "duration": 3.85}, {"text": "And so if you look at\nthis from the top view,", "start": 4782.78, "duration": 3.0}, {"text": "so looking at it\nstraight down, you'd", "start": 4785.78, "duration": 2.21}, {"text": "have this central piece\nwith this external piece", "start": 4787.99, "duration": 4.41}, {"text": "with the two half-channels that\nbasically can rotate around", "start": 4792.4, "duration": 5.61}, {"text": "the central stalk.", "start": 4798.01, "duration": 1.53}, {"text": "This is hooked up to\nthe gamma subunit of F1", "start": 4799.54, "duration": 3.21}, {"text": "in which drives\nrotational catalysis.", "start": 4802.75, "duration": 2.94}, {"text": "And how this works\nis that attached", "start": 4805.69, "duration": 2.01}, {"text": "to this inner piece that is\nopen to the half-channels", "start": 4807.7, "duration": 5.52}, {"text": "is an aspartate residue.", "start": 4813.22, "duration": 3.85}, {"text": "So this is an aspartic\nacid residue that's there.", "start": 4817.07, "duration": 4.28}, {"text": "And recall that aspartic\nacid, it's an acid.", "start": 4821.35, "duration": 5.46}, {"text": "So it can pick up a\nproton or release a proton", "start": 4826.81, "duration": 6.25}, {"text": "from its acid group\ndepending on the pH", "start": 4833.06, "duration": 4.53}, {"text": "on either side of the membrane.", "start": 4837.59, "duration": 1.93}, {"text": "And so, remember,\nthere's a different pH", "start": 4839.52, "duration": 2.51}, {"text": "on the two sides\nof the membrane.", "start": 4842.03, "duration": 4.15}, {"text": "And it's really that\ndifference in pH", "start": 4846.18, "duration": 4.37}, {"text": "that will allow favorable\nturning around this center", "start": 4850.55, "duration": 6.09}, {"text": "stalk.", "start": 4856.64, "duration": 1.07}, {"text": "And so the pH in the\nintermembrane space is lower.", "start": 4857.71, "duration": 4.42}, {"text": "So that means you're\nmore likely to favor", "start": 4862.13, "duration": 3.03}, {"text": "protonation of the aspartate.", "start": 4865.16, "duration": 2.37}, {"text": "It can then rotate, such as the\nchannel, that aspartate, is now", "start": 4867.53, "duration": 3.39}, {"text": "exposed to the other\nchannel, to the matrix side.", "start": 4870.92, "duration": 2.67}, {"text": "There, the pH is higher,\nso favors deprotonation.", "start": 4873.59, "duration": 3.81}, {"text": "And basically, this will\ndrive motion of this piece", "start": 4877.4, "duration": 5.16}, {"text": "around the central stalk.", "start": 4882.56, "duration": 1.71}, {"text": "That being coupled to\nthe gamma subunit of F1", "start": 4884.27, "duration": 3.95}, {"text": "will cause the rotation\nof the F1 subunit changing", "start": 4888.22, "duration": 5.29}, {"text": "the attached conformation of\nthe rest of the complex to favor", "start": 4893.51, "duration": 4.38}, {"text": "ATP synthesis.", "start": 4897.89, "duration": 1.53}, {"text": "And it's really this is\nhow moving of protons back", "start": 4899.42, "duration": 5.25}, {"text": "from the intermembrane\nspace to the matrix", "start": 4904.67, "duration": 2.4}, {"text": "can drive the synthesis of\nATP, the phosphorylation", "start": 4907.07, "duration": 3.51}, {"text": "part of this process.", "start": 4910.58, "duration": 3.64}, {"text": "And so now you\nhave a full picture", "start": 4914.22, "duration": 2.06}, {"text": "of how carbon oxidation really\nreleases energy in a way that's", "start": 4916.28, "duration": 5.29}, {"text": "coupled to do work in biology.", "start": 4921.57, "duration": 2.33}, {"text": "So we can, of course,\ncouple this directly,", "start": 4923.9, "duration": 2.22}, {"text": "as we did at GAPDH or\nsuccinic thiokinase.", "start": 4926.12, "duration": 3.93}, {"text": "But mostly, it's captured to\ncharge up these NAD/NADH ratios", "start": 4930.05, "duration": 5.58}, {"text": "where favorable\nelectron transport can", "start": 4935.63, "duration": 2.49}, {"text": "be used to make this delta psi\ndelta pH in a membrane that", "start": 4938.12, "duration": 3.87}, {"text": "can be used also to synthesize\nATP despite a high ATP/ADP", "start": 4941.99, "duration": 4.29}, {"text": "ratio because that battery can\nbe used to drive this machine.", "start": 4946.28, "duration": 8.46}, {"text": "Now, I want to point out\nthat the ATP synthase is just", "start": 4954.74, "duration": 3.0}, {"text": "like any other enzyme\nin any pathway.", "start": 4957.74, "duration": 3.13}, {"text": "And that is, if\nconditions are right,", "start": 4960.87, "duration": 1.82}, {"text": "there's no reason\nthat this machine", "start": 4962.69, "duration": 2.4}, {"text": "has to drive ATP synthesis.", "start": 4965.09, "duration": 2.07}, {"text": "It could also\nconsume ATP as a way", "start": 4967.16, "duration": 3.72}, {"text": "to create a proton gradient.", "start": 4970.88, "duration": 2.52}, {"text": "That is use ATP\nhydrolysis to pump", "start": 4973.4, "duration": 4.05}, {"text": "protons in the\nopposite direction", "start": 4977.45, "duration": 2.22}, {"text": "into the intermembrane space.", "start": 4979.67, "duration": 2.165}, {"text": "Well, why would\nyou ever do that?", "start": 4981.835, "duration": 1.375}, {"text": "Well, you would do that\nbecause having this battery", "start": 4983.21, "duration": 2.82}, {"text": "is useful because ATP is\nnot the only way that cells", "start": 4986.03, "duration": 3.93}, {"text": "can use energy to do work.", "start": 4989.96, "duration": 1.98}, {"text": "It turns out that having\na membrane potential", "start": 4991.94, "duration": 2.85}, {"text": "is useful for other things.", "start": 4994.79, "duration": 1.28}, {"text": "So if you're in\ncourse nine, you know", "start": 4996.07, "duration": 1.72}, {"text": "that action potentials are\ncarried, basically electricity", "start": 4997.79, "duration": 3.72}, {"text": "along cells.", "start": 5001.51, "duration": 1.74}, {"text": "What is that?", "start": 5003.25, "duration": 0.63}, {"text": "That is basically changing\nmembrane potentials", "start": 5003.88, "duration": 2.49}, {"text": "across cells.", "start": 5006.37, "duration": 1.5}, {"text": "More generally,\nmembrane potentials", "start": 5007.87, "duration": 1.71}, {"text": "can be used to do lots\nof other types of work.", "start": 5009.58, "duration": 3.45}, {"text": "And so ATP is only one way that\ncells can use biological energy", "start": 5013.03, "duration": 7.29}, {"text": "because it can be\ncoupled to otherwise", "start": 5020.32, "duration": 1.62}, {"text": "unfavorable reactions.", "start": 5021.94, "duration": 1.68}, {"text": "But you can also\ncouple ion gradients", "start": 5023.62, "duration": 2.34}, {"text": "to unfavorable reactions\nand use that to do work--", "start": 5025.96, "duration": 4.3}, {"text": "and so lots of useful\nways that delta psi delta", "start": 5030.26, "duration": 4.04}, {"text": "pH can be used by cells.", "start": 5034.3, "duration": 5.32}, {"text": "And so what are some of these?", "start": 5039.62, "duration": 1.37}, {"text": "Well, the first one is this\ncan be used to generate heat.", "start": 5040.99, "duration": 5.98}, {"text": "So if you're checking\nyour phone right now,", "start": 5046.97, "duration": 2.84}, {"text": "your phone is obviously\na very useful device", "start": 5049.81, "duration": 2.31}, {"text": "to do all kinds of work for you.", "start": 5052.12, "duration": 2.16}, {"text": "You can read whatever\nyou want on your phone,", "start": 5054.28, "duration": 2.43}, {"text": "use it to call people.", "start": 5056.71, "duration": 1.795}, {"text": "Well, what happens\nif you short circuit", "start": 5058.505, "duration": 1.625}, {"text": "the battery in your phone?", "start": 5060.13, "duration": 1.35}, {"text": "Well, it'll get really hot.", "start": 5061.48, "duration": 1.89}, {"text": "And the same thing happens here.", "start": 5063.37, "duration": 2.73}, {"text": "Rather than use this delta\npsi delta pH to generate ATP,", "start": 5066.1, "duration": 4.38}, {"text": "if I just put a hole\nin the membrane,", "start": 5070.48, "duration": 3.6}, {"text": "something referred to as\nan uncoupling protein, UCP,", "start": 5074.08, "duration": 3.9}, {"text": "Uncoupling Protein, this will\njust allow the leak of protons", "start": 5077.98, "duration": 4.53}, {"text": "back across the membrane.", "start": 5082.51, "duration": 2.37}, {"text": "Well, that's short\ncircuiting the battery.", "start": 5084.88, "duration": 2.55}, {"text": "Energy has to be\ndissipated somewhere,", "start": 5087.43, "duration": 1.74}, {"text": "and it's dissipated as heat.", "start": 5089.17, "duration": 2.76}, {"text": "And this is effectively ways in\nwhich biology can create heat.", "start": 5091.93, "duration": 6.36}, {"text": "And so uncoupling proteins are\nexpressed in a tissue called", "start": 5098.29, "duration": 2.94}, {"text": "brown fat in mammals.", "start": 5101.23, "duration": 2.34}, {"text": "Brown fat is a way\nto generate heat.", "start": 5103.57, "duration": 3.33}, {"text": "And it's one way that we\nmaintain our body temperatures.", "start": 5106.9, "duration": 3.3}, {"text": "Now, the system is imperfect.", "start": 5110.2, "duration": 1.53}, {"text": "And lots of cells,\nall metabolism,", "start": 5111.73, "duration": 2.64}, {"text": "generates some heat.", "start": 5114.37, "duration": 1.53}, {"text": "If you've ever done\ncomposting, you", "start": 5115.9, "duration": 1.86}, {"text": "know your compost pile gets hot.", "start": 5117.76, "duration": 2.31}, {"text": "That's because the\norganisms there", "start": 5120.07, "duration": 1.59}, {"text": "that are metabolized in the\nmaterial in the compost pile", "start": 5121.66, "duration": 3.27}, {"text": "are generating some heat.", "start": 5124.93, "duration": 1.347}, {"text": "And that's because\nmembranes aren't perfect.", "start": 5126.277, "duration": 1.833}, {"text": "They're somewhat leaky.", "start": 5128.11, "duration": 1.95}, {"text": "Now, as humans, we work hard\nto maintain a constant body", "start": 5130.06, "duration": 3.87}, {"text": "temperature.", "start": 5133.93, "duration": 1.02}, {"text": "And there's actually a\nhuge amount of energy", "start": 5134.95, "duration": 2.04}, {"text": "that goes into just maintaining\nour body temperature.", "start": 5136.99, "duration": 3.55}, {"text": "But you can imagine\nhow efficiently", "start": 5140.54, "duration": 2.54}, {"text": "we couple these processes will\ndetermine how many calories we", "start": 5143.08, "duration": 4.68}, {"text": "need to maintain heat.", "start": 5147.76, "duration": 2.04}, {"text": "And that's actually a\ntheory of weight control,", "start": 5149.8, "duration": 2.31}, {"text": "that those of us\nout there who have", "start": 5152.11, "duration": 2.07}, {"text": "less well-coupled\nmitochondria can", "start": 5154.18, "duration": 1.92}, {"text": "eat more because they waste\nmore energy in generating", "start": 5156.1, "duration": 3.18}, {"text": "heat than those of us who are\nreally efficient in doing this.", "start": 5159.28, "duration": 3.37}, {"text": "And in fact, there's\ndrugs that allow", "start": 5162.65, "duration": 1.76}, {"text": "you to uncouple\nelectron transport", "start": 5164.41, "duration": 3.47}, {"text": "generation of delta psi\ndelta pH from utilizing", "start": 5167.88, "duration": 3.66}, {"text": "that membrane potential.", "start": 5171.54, "duration": 2.16}, {"text": "And these are great\nweight loss drugs.", "start": 5173.7, "duration": 2.195}, {"text": "Dinitrophenol was used middle\npart of the last century", "start": 5175.895, "duration": 5.155}, {"text": "as a weight loss agent.", "start": 5181.05, "duration": 1.16}, {"text": "It was very effective.", "start": 5182.21, "duration": 1.76}, {"text": "The problem is it's also\nincredibly dangerous", "start": 5183.97, "duration": 2.11}, {"text": "because people will die.", "start": 5186.08, "duration": 1.0}, {"text": "Because it turns out, if\nyou uncouple this process", "start": 5187.08, "duration": 2.16}, {"text": "and you don't have enough\nATP, you die really fast.", "start": 5189.24, "duration": 3.04}, {"text": "And so don't use that\ndrug, but it illustrates", "start": 5192.28, "duration": 3.47}, {"text": "how you can use this\nbattery to generate", "start": 5195.75, "duration": 3.06}, {"text": "heat, another form of energy.", "start": 5198.81, "duration": 3.46}, {"text": "Another big one is\nmembrane transport.", "start": 5202.27, "duration": 4.37}, {"text": "So if I want to concentrate\nsomething-- and this", "start": 5210.4, "duration": 2.9}, {"text": "could be moving proteins.", "start": 5213.3, "duration": 3.72}, {"text": "Or it could be\nmoving other ions,", "start": 5217.02, "duration": 2.91}, {"text": "like in an action potential.", "start": 5219.93, "duration": 3.95}, {"text": "Those are unfavorable\nprocesses, right?", "start": 5223.88, "duration": 1.86}, {"text": "I'm causing dissociation\nof ions across membranes", "start": 5225.74, "duration": 4.68}, {"text": "or moving protein from one\nside of a membrane to another.", "start": 5230.42, "duration": 3.6}, {"text": "One can couple those transfer\nprocesses to these delta psi", "start": 5234.02, "duration": 4.77}, {"text": "delta pH as well.", "start": 5238.79, "duration": 1.63}, {"text": "And in fact, protein\nimport in the mitochondria", "start": 5240.42, "duration": 2.99}, {"text": "depends very much on\na membrane potential", "start": 5243.41, "duration": 3.27}, {"text": "to get those proteins in.", "start": 5246.68, "duration": 1.86}, {"text": "The mitochondria is\nan important site", "start": 5248.54, "duration": 1.89}, {"text": "of calcium storage for cells.", "start": 5250.43, "duration": 2.46}, {"text": "Calcium is concentrated\nin the mitochondria.", "start": 5252.89, "duration": 2.31}, {"text": "And that concentration\ncan be driven", "start": 5255.2, "duration": 2.37}, {"text": "by this membrane potential.", "start": 5257.57, "duration": 2.5}, {"text": "And of course, this\npotential can also", "start": 5260.07, "duration": 2.63}, {"text": "use to power lots of shuttles,\nlike the carnitine shuttle,", "start": 5262.7, "duration": 4.08}, {"text": "and actually create\nsituations where", "start": 5266.78, "duration": 2.07}, {"text": "you have different conditions\nacross membranes as a way", "start": 5268.85, "duration": 3.42}, {"text": "to favor different chemistries.", "start": 5272.27, "duration": 3.51}, {"text": "And so the last thing\nI want to mention", "start": 5275.78, "duration": 1.65}, {"text": "is, in fact, these\nshuttles, which is just ways", "start": 5277.43, "duration": 3.87}, {"text": "that one can couple\nmembrane potential to drive", "start": 5281.3, "duration": 3.96}, {"text": "other things, can also be\nreally important for how", "start": 5285.26, "duration": 3.33}, {"text": "metabolism works.", "start": 5288.59, "duration": 1.68}, {"text": "And I just want to illustrate\none aspect of this.", "start": 5290.27, "duration": 2.68}, {"text": "So if I draw here\nmy mitochondria--", "start": 5292.95, "duration": 3.323}, {"text": "let me draw it up here.", "start": 5296.273, "duration": 3.387}, {"text": "If I draw a\nmitochondria, so here's", "start": 5299.66, "duration": 7.32}, {"text": "all these processes\nare happening here", "start": 5306.98, "duration": 3.48}, {"text": "where we have electron\ntransport generating", "start": 5310.46, "duration": 4.17}, {"text": "a potential across the\nintermitochondrial membrane", "start": 5314.63, "duration": 3.69}, {"text": "that can be used\nto synthesize ATP.", "start": 5318.32, "duration": 4.78}, {"text": "Well, this synthesis is\noccurring in the mitochondria.", "start": 5323.1, "duration": 4.59}, {"text": "But ultimately, I need\nto get that ATP out", "start": 5327.69, "duration": 4.32}, {"text": "into the cytosol for it\nto be useful for the cell", "start": 5332.01, "duration": 5.25}, {"text": "to run otherwise unfavorable\nprocesses in the cytosol.", "start": 5337.26, "duration": 3.51}, {"text": "And so one needs a\ntransporter for this.", "start": 5340.77, "duration": 2.1}, {"text": "There's some transporter\ncalled the adenine nucleotide", "start": 5342.87, "duration": 2.25}, {"text": "transporter.", "start": 5345.12, "duration": 1.32}, {"text": "And this partially takes\nadvantage of the fact", "start": 5346.44, "duration": 3.48}, {"text": "that there's a charge\ndifference between ATP and ADP", "start": 5349.92, "duration": 4.43}, {"text": "to actually couple membrane\npotential to exchange", "start": 5354.35, "duration": 3.87}, {"text": "of ATP/ADP between the cytosol\nand the mitochondrial matrix.", "start": 5358.22, "duration": 6.15}, {"text": "Now, there's other issues we'll\ntalk about next time as well.", "start": 5364.37, "duration": 3.13}, {"text": "And so, remember,\nsome metabolism", "start": 5367.5, "duration": 2.57}, {"text": "is happening in the cytosol.", "start": 5370.07, "duration": 2.55}, {"text": "So glycolysis turning\nglucose into pyruvate", "start": 5372.62, "duration": 8.46}, {"text": "is occurring in the cytosol.", "start": 5381.08, "duration": 1.77}, {"text": "We've already discussed.", "start": 5382.85, "duration": 1.0}, {"text": "That means you got\nto get pyruvate", "start": 5383.85, "duration": 1.417}, {"text": "in the mitochondria\nfor the PDH reaction,", "start": 5385.267, "duration": 2.353}, {"text": "but this is also generating\nNADH in the cytosol.", "start": 5387.62, "duration": 4.35}, {"text": "And if that NADH needs\nto transfer its electrons", "start": 5391.97, "duration": 3.36}, {"text": "to oxygen, we also\nhave to get that", "start": 5395.33, "duration": 1.68}, {"text": "NADH into the mitochondrial\nmatrix or, more correctly,", "start": 5397.01, "duration": 5.16}, {"text": "transfer those electrons into\nthe mitochondrial matrix.", "start": 5402.17, "duration": 2.92}, {"text": "It turns out cells maintain\ndistinct NAD/NADH pools", "start": 5405.09, "duration": 3.68}, {"text": "in the mitochondria\nand the cytosol.", "start": 5408.77, "duration": 1.89}, {"text": "That's part of the\nconditions that", "start": 5410.66, "duration": 1.62}, {"text": "make different reactions\nfavorable in each compartment.", "start": 5412.28, "duration": 5.28}, {"text": "And how cells do that,\ntransfer those electrons", "start": 5417.56, "duration": 3.75}, {"text": "into the mitochondria, ends up\nbeing another important thing", "start": 5421.31, "duration": 3.75}, {"text": "that has to be transport that's\ndriven across these membranes", "start": 5425.06, "duration": 3.57}, {"text": "where one can use\ndelta psi delta pH.", "start": 5428.63, "duration": 3.09}, {"text": "And we'll talk about that at\nthe start of the next lecture.", "start": 5431.72, "duration": 2.77}, {"text": "Thanks.", "start": 5434.49, "duration": 1.55}] |