1 00:00:14,790 --> 00:00:21,150 PROFESSOR: Let's talk about what was probably the first 2 00:00:21,150 --> 00:00:24,442 energy producing system that evolved. 3 00:00:28,100 --> 00:00:32,840 The thought is when the earth first formed and the first 4 00:00:32,840 --> 00:00:36,530 primitive organisms, perhaps resembling a present-day 5 00:00:36,530 --> 00:00:39,550 bacterium in some way came out, there were a lot of 6 00:00:39,550 --> 00:00:41,970 organic compounds that had been aided by lightning 7 00:00:41,970 --> 00:00:45,410 strikes and cosmic radiations triggering chemical 8 00:00:45,410 --> 00:00:46,615 reactions and so on. 9 00:00:46,615 --> 00:00:49,980 So there was food around, but they depleted those resources 10 00:00:49,980 --> 00:00:51,820 in the same way we're depleting the petroleum 11 00:00:51,820 --> 00:00:53,180 resources right now. 12 00:00:53,180 --> 00:00:59,950 If life was going to continue, somehow a way had to be found 13 00:00:59,950 --> 00:01:01,790 to make energy. 14 00:01:01,790 --> 00:01:09,220 Glycolysis, it looks kind of complicated. 15 00:01:09,220 --> 00:01:13,760 It takes a molecule of sugar and then there are a series of 16 00:01:13,760 --> 00:01:21,060 10 chemical reactions, each catalyzed by a separate enzyme 17 00:01:21,060 --> 00:01:42,940 that give two molecules of this, molecules of pyruvate, 18 00:01:42,940 --> 00:01:51,990 plus two ATPs, plus two NADHs. 19 00:01:51,990 --> 00:01:55,320 Which tells you there must have been some kind of 20 00:01:55,320 --> 00:01:59,020 oxidation step as part of this sequence of events, because 21 00:01:59,020 --> 00:02:06,190 electrons got taken off and got stashed on this NADH. 22 00:02:06,190 --> 00:02:09,250 There are a couple of things that are important about this. 23 00:02:09,250 --> 00:02:14,340 One is its a pathway. 24 00:02:14,340 --> 00:02:19,600 It evolved probably 3.7 billion years ago or sometime, 25 00:02:19,600 --> 00:02:20,980 nobody really knows. 26 00:02:20,980 --> 00:02:22,990 But a long time ago. 27 00:02:22,990 --> 00:02:26,000 It's pretty much universal. 28 00:02:26,000 --> 00:02:29,037 Not perfectly so, but it's in bacteria, it's in 29 00:02:29,037 --> 00:02:31,045 yeast, it's in humans. 30 00:02:37,190 --> 00:02:45,220 And another really important thing is that it evolved early 31 00:02:45,220 --> 00:02:49,120 in the evolution of earth, so it evolved when there was no 32 00:02:49,120 --> 00:02:50,580 oxygen around. 33 00:02:50,580 --> 00:02:54,440 So it's a way of making energy from glucose in 34 00:02:54,440 --> 00:02:56,740 the absence of oxygen. 35 00:02:56,740 --> 00:03:00,280 Which is a really important thing as you'll 36 00:03:00,280 --> 00:03:01,920 see as we go along. 37 00:03:05,520 --> 00:03:10,080 You're not going to have to memorize this pathway. 38 00:03:10,080 --> 00:03:13,200 We'll give it to you if you need it. 39 00:03:13,200 --> 00:03:17,070 But you're going to need to understand its implications. 40 00:03:17,070 --> 00:03:19,300 And just let me point out a couple of things. 41 00:03:19,300 --> 00:03:23,340 You're going to see a sequence of 10 chemical transformations 42 00:03:23,340 --> 00:03:25,850 that in the end are going to end up with a couple of 43 00:03:25,850 --> 00:03:27,910 pyruvates being produced. 44 00:03:27,910 --> 00:03:30,220 And I'll try to explain to you why you 45 00:03:30,220 --> 00:03:35,010 should care about this. 46 00:03:35,010 --> 00:03:37,940 There's a concept that you're familiar with, that if you 47 00:03:37,940 --> 00:03:40,170 want to make something and you get a little start up company, 48 00:03:40,170 --> 00:03:41,980 what's the very first thing you have to do? 49 00:03:41,980 --> 00:03:44,060 You actually have to make an investment 50 00:03:44,060 --> 00:03:45,030 before you can get going. 51 00:03:45,030 --> 00:03:47,370 And you're out looking for venture capital things. 52 00:03:47,370 --> 00:03:49,840 Well one of the odd things about this, here's probably 53 00:03:49,840 --> 00:03:53,380 the first sequence of reactions that arose on earth 54 00:03:53,380 --> 00:03:56,520 within some organism and enabled that organism to make 55 00:03:56,520 --> 00:03:57,490 energy out of glucose. 56 00:03:57,490 --> 00:03:58,810 And look, the first thing that happens. 57 00:03:58,810 --> 00:04:02,270 Trying to make ATP, the very first thing it does is it 58 00:04:02,270 --> 00:04:04,370 spends an ATP. 59 00:04:04,370 --> 00:04:10,020 And it takes glucose, and it makes glucose 6-phosphate. 60 00:04:10,020 --> 00:04:11,420 Go down a couple of steps. 61 00:04:11,420 --> 00:04:16,769 There's an enzyme that takes another molecule of ATP. 62 00:04:16,769 --> 00:04:19,110 And now you've got this point. 63 00:04:19,110 --> 00:04:22,130 You're at fructose with two phosphates on it. 64 00:04:22,130 --> 00:04:25,560 If this was your venture capital, we'd say, guys, how 65 00:04:25,560 --> 00:04:26,400 about some product? 66 00:04:26,400 --> 00:04:29,760 Stop spending, stop spending money. 67 00:04:29,760 --> 00:04:33,520 But at this point then, this is a 6-carbon sugar. 68 00:04:33,520 --> 00:04:40,970 And it gets split into two 3-carbon compounds that are 69 00:04:40,970 --> 00:04:42,720 going back and forth. 70 00:04:42,720 --> 00:04:43,550 Oh I can see it. 71 00:04:43,550 --> 00:04:44,800 It's over there, OK. 72 00:04:52,800 --> 00:04:55,740 In equilibrium over here. 73 00:04:55,740 --> 00:04:59,650 And this particular 3-carbon compound then 74 00:04:59,650 --> 00:05:04,820 goes on to be oxidized. 75 00:05:04,820 --> 00:05:08,030 You get the production of NADH. 76 00:05:08,030 --> 00:05:11,570 And at that point, this molecule has a lot of energy 77 00:05:11,570 --> 00:05:14,430 stored in it, and in the next transformation this cell is 78 00:05:14,430 --> 00:05:16,960 able to make two ATPs. 79 00:05:16,960 --> 00:05:18,820 And it gets back the initial investment. 80 00:05:18,820 --> 00:05:21,320 It goes all the way through the rest of the pathway. 81 00:05:21,320 --> 00:05:25,650 And the very last step, you get two more ATPs back. 82 00:05:25,650 --> 00:05:28,000 There's your net yield. 83 00:05:28,000 --> 00:05:37,610 So what you get out of this are 4ATP+2NADH, and your 84 00:05:37,610 --> 00:05:41,380 investment was two ATPs. 85 00:05:41,380 --> 00:05:45,720 So your net 2ATP+NADH. 86 00:05:50,430 --> 00:05:52,640 Why is this cell going and doing these initial 87 00:05:52,640 --> 00:05:53,240 investments? 88 00:05:53,240 --> 00:05:58,280 Well if we look at the changes in free energy associated with 89 00:05:58,280 --> 00:06:01,110 what's going on, there's glucose up in the upper left 90 00:06:01,110 --> 00:06:04,710 starting up there, and there's pyruvate down there. 91 00:06:04,710 --> 00:06:08,010 So you're going energetically downhill in the end. 92 00:06:08,010 --> 00:06:11,350 So this is a sequence of events that, in principle, you 93 00:06:11,350 --> 00:06:13,660 should be able to get some energy out of it. 94 00:06:13,660 --> 00:06:17,570 But for reasons that may seem obscure to you at this point, 95 00:06:17,570 --> 00:06:21,040 before it gets to the point of making energy, it undergoes a 96 00:06:21,040 --> 00:06:24,590 set of transformations that's pushing the reaction. 97 00:06:24,590 --> 00:06:28,870 It requires the reactants to go energetically uphill, i.e. 98 00:06:28,870 --> 00:06:31,590 in an unfavorable direction. 99 00:06:31,590 --> 00:06:36,960 So what the cell does is, by coupling ATP hydrolysis to 100 00:06:36,960 --> 00:06:40,220 this step, it makes that reaction go. 101 00:06:40,220 --> 00:06:43,780 Here's another unfavorable one that makes that one go by 102 00:06:43,780 --> 00:06:46,360 coupling ATP hydrolysis to it. 103 00:06:46,360 --> 00:06:50,590 This is an uphill reaction, but look over here. 104 00:06:50,590 --> 00:06:54,710 This is an immensely favorable reaction that goes essentially 105 00:06:54,710 --> 00:06:55,150 to completion. 106 00:06:55,150 --> 00:06:56,570 It goes all the way. 107 00:06:56,570 --> 00:06:59,480 So that means this product is just being continually taken 108 00:06:59,480 --> 00:07:02,780 out of the system, so the equilibrium is basically being 109 00:07:02,780 --> 00:07:06,520 pulled over the edge by the removal of that product. 110 00:07:06,520 --> 00:07:08,270 This is where the oxidation takes place. 111 00:07:08,270 --> 00:07:11,580 You get the NADH made right there. 112 00:07:11,580 --> 00:07:15,770 And it's finally down here where you've got to lose. 113 00:07:15,770 --> 00:07:21,080 This transformation gives you two ATPs and later there's 114 00:07:21,080 --> 00:07:21,930 another one. 115 00:07:21,930 --> 00:07:25,690 Let me just give you a sense of why you 116 00:07:25,690 --> 00:07:28,540 get ATP at that step. 117 00:07:28,540 --> 00:07:36,460 The compound that you have at that point is 1, 3 118 00:07:36,460 --> 00:07:37,710 diphosphoglycerate. 119 00:07:49,860 --> 00:07:52,710 Or sometimes this is called bis, is also 120 00:07:52,710 --> 00:07:53,930 used to describe this. 121 00:07:53,930 --> 00:07:56,750 But what is this compound? 122 00:07:56,750 --> 00:07:59,770 It's a 3-carbon compound. 123 00:08:11,870 --> 00:08:18,020 So glycerate is basically an oxidized version of glycerol 124 00:08:18,020 --> 00:08:21,080 that has been oxidized up to a carboxyl acid. 125 00:08:21,080 --> 00:08:26,230 So this is a mixed anhydride between carboxyl acid and a 126 00:08:26,230 --> 00:08:27,400 phosphate ion. 127 00:08:27,400 --> 00:08:31,210 So that's a very reactive and unstable compound. 128 00:08:31,210 --> 00:08:33,980 And the other thing that the cell has succeeded in doing by 129 00:08:33,980 --> 00:08:36,669 all of these transformations is it's got these two 130 00:08:36,669 --> 00:08:39,760 phosphates with all their negative charges in. 131 00:08:39,760 --> 00:08:43,010 So this is a compound that would very much like to move 132 00:08:43,010 --> 00:08:46,230 to a lower energy. 133 00:08:46,230 --> 00:08:51,000 So you can get rid of this phosphate and move to an 134 00:08:51,000 --> 00:08:54,320 energy level, use that energy to make ATP. 135 00:08:54,320 --> 00:08:58,240 And there's a similar kind of logic that explains why you 136 00:08:58,240 --> 00:09:01,510 get energy out of the final step when you look at it. 137 00:09:01,510 --> 00:09:07,760 So there's several points, I guess, to make out of this. 138 00:09:07,760 --> 00:09:10,330 One is its pathway. 139 00:09:10,330 --> 00:09:15,380 None of these reactions make any particular sense by 140 00:09:15,380 --> 00:09:16,990 themselves. 141 00:09:16,990 --> 00:09:19,120 You could have a cell that knew how to do one of them and 142 00:09:19,120 --> 00:09:21,170 it would gain nothing. 143 00:09:21,170 --> 00:09:26,040 Unless you wanted to use the product to make something. 144 00:09:26,040 --> 00:09:28,720 This thing only makes sense, these reactions only make 145 00:09:28,720 --> 00:09:32,810 sense in the context of this 10 step pathway. 146 00:09:32,810 --> 00:09:37,200 And each step in that pathway we were looking at is 147 00:09:37,200 --> 00:09:40,080 catalyzed by a different enzyme. 148 00:09:40,080 --> 00:09:43,040 So for an organism to pull this off, the first one that 149 00:09:43,040 --> 00:09:49,670 did it had to collect in one cell all 10 of those enzymes. 150 00:09:49,670 --> 00:09:53,870 And probably there is the reason that this is such a 151 00:09:53,870 --> 00:09:55,720 complicated system. 152 00:09:55,720 --> 00:09:58,040 If you were sitting as a designer you might be able to 153 00:09:58,040 --> 00:10:03,080 come up now with a more efficient way to get ATP out. 154 00:10:03,080 --> 00:10:06,880 But what happened evolutionarily was some bug 155 00:10:06,880 --> 00:10:09,910 somewhere got all of these things together, and now 156 00:10:09,910 --> 00:10:11,210 suddenly it could make energy. 157 00:10:11,210 --> 00:10:15,360 So it had a huge advantage over everybody else. 158 00:10:15,360 --> 00:10:20,110 And once it took over, that system took over, then it 159 00:10:20,110 --> 00:10:22,820 became universal. 160 00:10:22,820 --> 00:10:25,440 Whether it was the best that ever could be designed, it 161 00:10:25,440 --> 00:10:29,100 doesn't matter, because it had an evolutionary edge. 162 00:10:29,100 --> 00:10:32,700 And that's so, to some extent, we're looking at a living 163 00:10:32,700 --> 00:10:34,120 fossil, biochemical. 164 00:10:34,120 --> 00:10:39,750 But it's in bacteria, it's in yeast, and it's going on 165 00:10:39,750 --> 00:10:41,320 inside of our body. 166 00:10:41,320 --> 00:10:44,790 Another principle that I think you can see here, which I've 167 00:10:44,790 --> 00:10:50,260 been trying to say, is in this case, the energy consuming 168 00:10:50,260 --> 00:10:54,030 reactions are driven by coupling them to the 169 00:10:54,030 --> 00:10:55,400 hydrolysis of ATP. 170 00:10:55,400 --> 00:10:58,740 The cell spends a bit of its energy money to get these 171 00:10:58,740 --> 00:11:01,440 intermediates, knowing that it's invest-- 172 00:11:01,440 --> 00:11:05,160 well not knowing, but at least conceptually anyway, knowing 173 00:11:05,160 --> 00:11:09,650 that it's going to get its investment back. 174 00:11:09,650 --> 00:11:13,400 And then the reactions that release energy are used to 175 00:11:13,400 --> 00:11:16,770 drive the synthesis of ATP. 176 00:11:16,770 --> 00:11:20,830 And you'll begin to see, we're going to just talk about some 177 00:11:20,830 --> 00:11:24,090 other aspects of this in just a minute. 178 00:11:24,090 --> 00:11:25,850 So, what do you think? 179 00:11:25,850 --> 00:11:28,850 You're the first bug and you've got this and nobody 180 00:11:28,850 --> 00:11:32,420 else can do it, so you can start charging away. 181 00:11:32,420 --> 00:11:33,360 What do we need to do? 182 00:11:33,360 --> 00:11:36,000 We just let this thing cycle away? 183 00:11:36,000 --> 00:11:37,780 The stuff that I had up there, is it going to work? 184 00:11:42,630 --> 00:11:43,460 There's a problem. 185 00:11:43,460 --> 00:11:44,820 Anybody see what the problem is? 186 00:11:51,350 --> 00:11:55,320 We're making two molecules of ATP and two molecules of NADH. 187 00:11:58,272 --> 00:12:00,240 Talk to the person beside you. 188 00:12:00,240 --> 00:12:04,394 Figure out why something else has to happen. 189 00:12:04,394 --> 00:12:05,876 Go ahead. 190 00:12:05,876 --> 00:12:07,358 See if you've got any ideas. 191 00:12:27,612 --> 00:12:29,290 We're going to keep doing this, over and 192 00:12:29,290 --> 00:12:31,070 over and over again. 193 00:12:31,070 --> 00:12:34,034 AUDIENCE: [INAUDIBLE]. 194 00:12:34,034 --> 00:12:35,516 Where's the first ATP? 195 00:12:35,516 --> 00:12:38,040 Where's the first ATP? 196 00:12:38,040 --> 00:12:39,990 PROFESSOR: OK, let's imagine for the-- 197 00:12:39,990 --> 00:12:43,880 I don't think this process could have invented ATP, it 198 00:12:43,880 --> 00:12:45,540 had to have been around, because many of the 199 00:12:45,540 --> 00:12:49,010 enzymes used it. 200 00:12:49,010 --> 00:12:51,940 What else is being used in this thing though? 201 00:12:57,160 --> 00:12:58,553 Did I hear NAD? 202 00:13:02,956 --> 00:13:06,610 To make this thing work, I have to keep taking NADs out 203 00:13:06,610 --> 00:13:09,400 of my pocket and putting it in the reaction, or it isn't 204 00:13:09,400 --> 00:13:12,040 going to go anywhere. 205 00:13:12,040 --> 00:13:14,870 So this isn't such a great invention at the moment. 206 00:13:14,870 --> 00:13:21,460 We have to do something to get the NADH back to NAD+ so we 207 00:13:21,460 --> 00:13:25,300 can do another molecule of glucose. 208 00:13:25,300 --> 00:13:25,835 You guys see? 209 00:13:25,835 --> 00:13:26,660 Do you see this? 210 00:13:26,660 --> 00:13:29,520 This is really, really an important consideration. 211 00:13:29,520 --> 00:13:36,160 So in order for cells to make energy using glycolysis in the 212 00:13:36,160 --> 00:13:39,150 absence of oxygen, which is when it evolved, they have to 213 00:13:39,150 --> 00:13:44,700 do something with that NADH or it's only going to use up the 214 00:13:44,700 --> 00:13:49,060 few molecules of NAD+ in the cell, and then it stops. 215 00:13:49,060 --> 00:13:52,570 And so there are two ways that nature's figured. 216 00:13:52,570 --> 00:13:54,820 Major ways nature had figured out how to do that. 217 00:13:59,160 --> 00:14:02,200 So here's a molecule of pyruvate. 218 00:14:05,730 --> 00:14:06,980 I got an extra. 219 00:14:12,250 --> 00:14:14,300 Something was nagging at me when I did this here. 220 00:14:17,370 --> 00:14:20,380 Sorry about that. 221 00:14:20,380 --> 00:14:24,570 It's always hard to see things when you're up at the board. 222 00:14:24,570 --> 00:14:24,900 OK. 223 00:14:24,900 --> 00:14:26,710 Molecule of pyruvate. 224 00:14:26,710 --> 00:14:30,270 There's a couple of solutions that have been arrived at. 225 00:14:30,270 --> 00:14:36,580 One is to take NADH, 2NADH, this is 2H+. 226 00:14:36,580 --> 00:14:47,620 Convert, make these back into 2NAD+, and to take those 227 00:14:47,620 --> 00:14:55,320 electrons and put them on the pyruvate to give this 228 00:14:55,320 --> 00:15:02,340 molecule, which is lactic acid. 229 00:15:02,340 --> 00:15:04,650 So by parking the electrons there, the cell is able to 230 00:15:04,650 --> 00:15:07,570 recycle the NADH. 231 00:15:07,570 --> 00:15:10,490 And lactic acid, we've run into that. 232 00:15:10,490 --> 00:15:15,250 That's why I showed you this picture of yogurt. 233 00:15:15,250 --> 00:15:19,530 The lactobacilli that make yogurt take the sugars that 234 00:15:19,530 --> 00:15:22,760 are present in milk and make them into lactic acid. 235 00:15:22,760 --> 00:15:24,850 And what's interesting in their case is they, even 236 00:15:24,850 --> 00:15:28,350 though there's oxygen around, they don't do respiration, 237 00:15:28,350 --> 00:15:30,100 which you'll see you can get more energy. 238 00:15:30,100 --> 00:15:35,500 They want it to get very acidic because that prevents 239 00:15:35,500 --> 00:15:37,120 their competitors from growing. 240 00:15:37,120 --> 00:15:40,570 And that's why you can leave yogurt sitting out on the 241 00:15:40,570 --> 00:15:42,900 tabletop and it'll be OK for quite a while. 242 00:15:42,900 --> 00:15:45,660 Whereas if you left some milk or something it'll go bad 243 00:15:45,660 --> 00:15:46,910 almost right away. 244 00:15:49,430 --> 00:15:51,650 Here's another example of when we run into it. 245 00:15:51,650 --> 00:15:55,400 When we do hard aerobic exercise, when you're running 246 00:15:55,400 --> 00:15:57,720 or skating really hard, things you see in the Olympics all 247 00:15:57,720 --> 00:16:03,125 the time, you deplete the oxygen supply in your blood 248 00:16:03,125 --> 00:16:05,580 when you do hard anaerobic exercise. 249 00:16:05,580 --> 00:16:10,770 And so the cells have the same problem of regenerating NADH. 250 00:16:10,770 --> 00:16:12,910 The way they solve it is they make the lactic acid. 251 00:16:12,910 --> 00:16:15,570 And that contributes to the sore muscles you feel after 252 00:16:15,570 --> 00:16:20,830 you've done hard anaerobic training. 253 00:16:20,830 --> 00:16:29,990 The other way of handling this is to take the 2NADH plus two 254 00:16:29,990 --> 00:16:39,460 hydrogen ions to make it into acetaldehyde, two 255 00:16:39,460 --> 00:16:40,710 acetaldehydes. 256 00:16:44,580 --> 00:16:46,834 Plus two CO2s. 257 00:16:46,834 --> 00:16:48,466 Oops, excuse me. 258 00:16:48,466 --> 00:16:51,430 Let's do this first. 259 00:16:51,430 --> 00:16:57,960 And then take the 2NADH plus the 2H+. 260 00:16:57,960 --> 00:17:02,740 Convert this to 2NAD+, and what we get out of this are 261 00:17:02,740 --> 00:17:11,470 two molecules of ethanol plus two molecules of CO2. 262 00:17:11,470 --> 00:17:16,510 Again, a process that's very similar to you, familiar to 263 00:17:16,510 --> 00:17:19,369 you, when I was showing you yeast growing. 264 00:17:19,369 --> 00:17:22,790 What yeast is doing is it's carrying out glycolysis and 265 00:17:22,790 --> 00:17:25,869 then it's taking those extra electrons, putting them on the 266 00:17:25,869 --> 00:17:29,755 pyruvate and making ethanol and carbon dioxide. 267 00:17:32,360 --> 00:17:35,520 I think there's a fermentation with what we call a 268 00:17:35,520 --> 00:17:36,750 fermentation with yeast. 269 00:17:36,750 --> 00:17:40,700 I think in that case they're making bourbon whiskey. 270 00:17:40,700 --> 00:17:44,130 Wine making, beer making, it's all the same thing. 271 00:17:44,130 --> 00:17:48,980 You have yeast, you're converting the sugars first to 272 00:17:48,980 --> 00:17:55,150 pyruvate, and then making ethanol and carboxylic acid. 273 00:17:55,150 --> 00:17:56,880 So anyway. 274 00:17:56,880 --> 00:18:01,320 There's no energy gain out of this, but these 275 00:18:01,320 --> 00:18:03,320 are important processes. 276 00:18:03,320 --> 00:18:04,570 They're called fermentation. 277 00:18:12,060 --> 00:18:16,590 And they can happen when there's no oxygen around. 278 00:18:16,590 --> 00:18:24,950 If you recall, there's a version of photosynthesis, 279 00:18:24,950 --> 00:18:27,660 what I called the second release of photosynthesis that 280 00:18:27,660 --> 00:18:31,280 began to evolve oxygen as a waste product. 281 00:18:31,280 --> 00:18:37,250 And then over the next ensuing millennia, the levels of 282 00:18:37,250 --> 00:18:40,920 oxygen slowly, slowly began to rise on earth. 283 00:18:40,920 --> 00:18:45,170 And as oxygen levels got to higher levels, and recall the 284 00:18:45,170 --> 00:18:48,990 Cambrian period, which is down on the fourth 285 00:18:48,990 --> 00:18:50,210 blackboard down there. 286 00:18:50,210 --> 00:18:52,890 We were only still even there half a billion years ago. 287 00:18:52,890 --> 00:18:55,840 We were only about 5% the present oxygen levels. 288 00:18:55,840 --> 00:19:02,690 But as oxygen levels arose, new metabolic opportunities 289 00:19:02,690 --> 00:19:03,485 became available. 290 00:19:03,485 --> 00:19:07,290 And in particular, cells were able to get at that energy 291 00:19:07,290 --> 00:19:10,160 which is stored in NADH. 292 00:19:10,160 --> 00:19:12,890 In the absence of oxygen, NADH is just a nuisance. 293 00:19:12,890 --> 00:19:14,390 You've got to get rid of it. 294 00:19:14,390 --> 00:19:16,010 But as you'll see in a minute, you can do something 295 00:19:16,010 --> 00:19:18,230 interesting if you have oxygen around. 296 00:19:18,230 --> 00:19:21,860 So just to look at this from a broad perspective, if we have 297 00:19:21,860 --> 00:19:26,260 glucose and we have all these little steps going along to 298 00:19:26,260 --> 00:19:35,490 give the two pyruvate, if there's, in the absence of 299 00:19:35,490 --> 00:19:50,380 oxygen, they get 2 lactate or we can get 2 ethanol, 2CO2. 300 00:19:53,320 --> 00:19:54,690 And in both cases, 2ATP. 301 00:19:59,240 --> 00:20:01,010 2ATP. 302 00:20:01,010 --> 00:20:06,710 These processes happening in the absence of oxygen to get 303 00:20:06,710 --> 00:20:11,010 rid of the, or at least not requiring oxygen in any case 304 00:20:11,010 --> 00:20:12,600 called fermentations. 305 00:20:12,600 --> 00:20:20,490 However, when oxygen is available, it became possible 306 00:20:20,490 --> 00:20:24,630 to evolve a new system for handling these pyruvates. 307 00:20:24,630 --> 00:20:29,650 We go into a biochemical cycle known as 308 00:20:29,650 --> 00:20:34,305 the citric acid cycle. 309 00:20:34,305 --> 00:20:36,920 And I'll say a word about this in a minute. 310 00:20:36,920 --> 00:20:44,250 Plus something else that's known as oxidative 311 00:20:44,250 --> 00:20:45,500 phosphorylation. 312 00:20:52,940 --> 00:20:56,100 This is also referred to as the respiratory chain. 313 00:21:01,180 --> 00:21:05,710 And what these two sets of processes together, enable the 314 00:21:05,710 --> 00:21:10,960 cell to take these two 3-carbon compounds and take 315 00:21:10,960 --> 00:21:15,120 them all the way down to six molecules of carbon dioxide, 316 00:21:15,120 --> 00:21:18,920 six molecules of water. 317 00:21:18,920 --> 00:21:29,010 And to make a net yield of 36 molecules of ATP. 318 00:21:29,010 --> 00:21:31,710 So if you go by fermentation a molecule of sugar 319 00:21:31,710 --> 00:21:33,650 gives you two ATPs. 320 00:21:33,650 --> 00:21:38,300 If you go by glycolysis and then follow it by respiration, 321 00:21:38,300 --> 00:21:39,130 you get 36. 322 00:21:39,130 --> 00:21:48,350 So respiration using oxygen, 18 times more efficient than 323 00:21:48,350 --> 00:21:50,160 by glycolysis. 324 00:21:50,160 --> 00:21:56,330 So in order to understand how this works though, we have to 325 00:21:56,330 --> 00:22:01,240 talk more about how you change from one form 326 00:22:01,240 --> 00:22:02,930 of energy to another. 327 00:22:02,930 --> 00:22:06,275 And it's interesting, although this process had to have 328 00:22:06,275 --> 00:22:10,310 evolved billions of years ago, it was only relatively 329 00:22:10,310 --> 00:22:14,790 recently that we understood the principal that was 330 00:22:14,790 --> 00:22:18,460 necessary for this kind of thing to happen. 331 00:22:18,460 --> 00:22:29,460 It's known as the Chemiosmotic Hypothesis. 332 00:22:29,460 --> 00:22:40,740 It was proposed by Peter Mitchell in 1961. 333 00:22:40,740 --> 00:22:44,550 He eventually got a Nobel Prize for it. 334 00:22:44,550 --> 00:22:49,780 It took quite a long time, it took more than 10 years for it 335 00:22:49,780 --> 00:22:50,630 to be accepted. 336 00:22:50,630 --> 00:22:54,310 In fact when I was in grad school in the mid '70s, people 337 00:22:54,310 --> 00:22:57,680 were still arguing whether this made sense or not. 338 00:22:57,680 --> 00:22:59,340 So here's the way it works. 339 00:22:59,340 --> 00:23:02,390 And we have to consider first three different forms of 340 00:23:02,390 --> 00:23:07,070 chemical energy that can be all interconverted. 341 00:23:07,070 --> 00:23:10,110 One of them is familiar to you, we've been talking about 342 00:23:10,110 --> 00:23:11,270 it all along. 343 00:23:11,270 --> 00:23:12,990 It's a chemical bond. 344 00:23:12,990 --> 00:23:15,745 Energy can be stored in a high energy bond. 345 00:23:15,745 --> 00:23:22,480 And if we break it to get ADP, an inorganic phosphate, we can 346 00:23:22,480 --> 00:23:24,135 release energy. 347 00:23:24,135 --> 00:23:26,600 However there's another way of storing energy as a 348 00:23:26,600 --> 00:23:27,850 concentration gradient. 349 00:23:30,980 --> 00:23:36,160 The principal here would be to have a barrier, which in this 350 00:23:36,160 --> 00:23:43,240 case is the cell membrane, and to have a high concentration 351 00:23:43,240 --> 00:23:49,460 of whatever it is on one side, and a low concentration on the 352 00:23:49,460 --> 00:23:50,710 other side. 353 00:23:50,710 --> 00:23:53,840 And there's energy stored in that. 354 00:23:53,840 --> 00:23:56,080 If you give it a chance it'll get to be the same 355 00:23:56,080 --> 00:23:58,240 concentration on both sides. 356 00:23:58,240 --> 00:24:01,950 And the trick is to have whatever the substance is, is 357 00:24:01,950 --> 00:24:09,920 to have a protein in the membrane that can permit this 358 00:24:09,920 --> 00:24:12,510 thing to go across in a controlled fashion. 359 00:24:12,510 --> 00:24:14,960 The third form is electrical potential. 360 00:24:22,160 --> 00:24:36,340 Again, the membrane actually acts as an insulator, and all 361 00:24:36,340 --> 00:24:52,540 cells, if this is the inside, and this is the outside, 362 00:24:52,540 --> 00:24:59,310 there's a gradient of hydrogen ions, so there are more 363 00:24:59,310 --> 00:25:03,810 hydrogen ions outside the cell than there are inside. 364 00:25:03,810 --> 00:25:09,450 So it creates an electrical potential. 365 00:25:09,450 --> 00:25:14,740 And these can't cross the membrane unless, guess what? 366 00:25:14,740 --> 00:25:17,560 There's a protein in the membrane that's able to permit 367 00:25:17,560 --> 00:25:20,190 their passage under controlled circumstances. 368 00:25:20,190 --> 00:25:24,760 So there's basically three different forms of energy that 369 00:25:24,760 --> 00:25:26,750 can be interconverted. 370 00:25:26,750 --> 00:25:29,660 And Peter Mitchell's great insight, which I will say was 371 00:25:29,660 --> 00:25:35,730 not intuitive for many people, was the combination, so the 372 00:25:35,730 --> 00:25:53,530 combo of this proton concentration gradient plus 373 00:25:53,530 --> 00:26:07,580 the electrical potential, could be used to drive the 374 00:26:07,580 --> 00:26:11,920 synthesis of ATP. 375 00:26:16,930 --> 00:26:19,190 And let me just say a couple of words. 376 00:26:19,190 --> 00:26:22,805 Because this may feel, how could this be? 377 00:26:22,805 --> 00:26:24,500 Could you really have energy? 378 00:26:24,500 --> 00:26:33,242 Well the potential across a cell is about 70 millivolts. 379 00:26:33,242 --> 00:26:35,690 May not seem all that much. 380 00:26:35,690 --> 00:26:42,720 But remember the membrane is about three nanometers thick. 381 00:26:42,720 --> 00:26:50,340 So that's about 200,000 volts per centimeter. 382 00:26:50,340 --> 00:26:55,620 High tension wires are 200,000 volts per mile or something. 383 00:26:55,620 --> 00:26:57,880 There's a lot of power in there. 384 00:26:57,880 --> 00:27:01,500 And furthermore, let's see if I can bring this up. 385 00:27:01,500 --> 00:27:04,060 I've been showing you this little 386 00:27:04,060 --> 00:27:05,380 movie a couple of times. 387 00:27:05,380 --> 00:27:08,040 The bacteria with these little nanomotors are spinning those 388 00:27:08,040 --> 00:27:11,900 flagella, and we saw how there's this machinery that's 389 00:27:11,900 --> 00:27:12,840 a little nanomotor. 390 00:27:12,840 --> 00:27:15,150 You know how it's powered? 391 00:27:15,150 --> 00:27:18,850 It's powered by the proton gradient. 392 00:27:18,850 --> 00:27:22,880 A proton trickles its way through this apparatus from 393 00:27:22,880 --> 00:27:24,460 the outside to the inside. 394 00:27:24,460 --> 00:27:26,010 It's coming down the gradient. 395 00:27:26,010 --> 00:27:28,600 That's the source of the power. 396 00:27:28,600 --> 00:27:31,310 And as I showed you, it's a pretty powerful motor. 397 00:27:31,310 --> 00:27:34,990 You can basically glue the propeller to a slide and it 398 00:27:34,990 --> 00:27:38,010 can twirl the bacteria all around. 399 00:27:38,010 --> 00:27:44,040 In fact, one of my favorite demos is, years ago people 400 00:27:44,040 --> 00:27:47,040 took a bacterium, and they managed to pop it open. 401 00:27:47,040 --> 00:27:53,280 So all the cytoplasm, all of the stuff on the inside came 402 00:27:53,280 --> 00:27:57,130 out of the cell, and you just got buffer on the inside. 403 00:27:57,130 --> 00:27:59,530 But it had these flagella. 404 00:27:59,530 --> 00:28:06,950 So you had just shells of bacteria with nothing really 405 00:28:06,950 --> 00:28:07,990 inside them. 406 00:28:07,990 --> 00:28:12,850 But, if you add a drop of acid to this media, now you've 407 00:28:12,850 --> 00:28:18,500 created a proton gradient with more protons on the outside 408 00:28:18,500 --> 00:28:20,970 than are on the inside, and guess what happens? 409 00:28:20,970 --> 00:28:24,540 The flagella motor starts working, and the bacteria 410 00:28:24,540 --> 00:28:27,710 start swimming, even though all the air, talk about dead 411 00:28:27,710 --> 00:28:29,640 man walking or something like that. 412 00:28:29,640 --> 00:28:35,080 It gives you an idea of the power that's in this 413 00:28:35,080 --> 00:28:40,720 combination of the proton gradient and 414 00:28:40,720 --> 00:28:42,210 the electric potential. 415 00:28:42,210 --> 00:28:49,970 The combination of this is often referred to as the 416 00:28:49,970 --> 00:28:51,230 proton motive force. 417 00:29:00,040 --> 00:29:02,450 So here's the principle of how the cell is 418 00:29:02,450 --> 00:29:04,220 able to exploit that. 419 00:29:04,220 --> 00:29:08,800 And this is what underlies respiration. 420 00:29:08,800 --> 00:29:10,050 There are two stages. 421 00:29:13,070 --> 00:29:19,810 Stage one, there's a membrane with some kind of membrane 422 00:29:19,810 --> 00:29:27,510 protein in it, which is actually a protein, functions 423 00:29:27,510 --> 00:29:31,300 as a proton pump. 424 00:29:31,300 --> 00:29:36,310 So it's a protein that's designed to be embedded into a 425 00:29:36,310 --> 00:29:39,640 membrane and to work there. 426 00:29:39,640 --> 00:29:43,550 This part here is the membrane itself. 427 00:29:43,550 --> 00:29:52,340 The proton gets transported from the inside to the outside 428 00:29:52,340 --> 00:29:57,350 when energy is put into this proton pump. 429 00:29:57,350 --> 00:30:03,160 So in response to some energy producing event, the cell 430 00:30:03,160 --> 00:30:08,790 pumps protons from its inside to its outside, and this then 431 00:30:08,790 --> 00:30:11,415 establishes the proton gradient. 432 00:30:22,160 --> 00:30:31,590 The second phase, then, is to take advantage of that proton 433 00:30:31,590 --> 00:30:37,160 gradient, and there's a different protein embedded in 434 00:30:37,160 --> 00:30:38,676 the membrane. 435 00:30:38,676 --> 00:30:43,890 It's known as an ATP synthase. 436 00:30:43,890 --> 00:30:51,550 And it permits a proton to come down the gradient, which 437 00:30:51,550 --> 00:30:52,880 you would want to do. 438 00:30:52,880 --> 00:30:54,830 But if that's all that happened, all you'd do is 439 00:30:54,830 --> 00:30:56,960 you'd just dissipate your gradient. 440 00:30:56,960 --> 00:31:02,580 So the key here is that this proton is only allowed to come 441 00:31:02,580 --> 00:31:06,530 down the gradient to the energetically more favorable 442 00:31:06,530 --> 00:31:12,750 side if ADP and inorganic phosphate are bound to this 443 00:31:12,750 --> 00:31:14,380 ATP synthase. 444 00:31:14,380 --> 00:31:18,340 And the dropping of the proton down the gradient's passage 445 00:31:18,340 --> 00:31:22,900 through this ATP synthase, which is an energy favorable 446 00:31:22,900 --> 00:31:26,400 reaction, drives the synthesis of ATP. 447 00:31:29,190 --> 00:31:31,850 So much energy is basically given off with this, you can 448 00:31:31,850 --> 00:31:35,970 make an ATP and the thing will still go. 449 00:31:35,970 --> 00:31:41,910 Now interestingly, this ATP synthase, which really lies at 450 00:31:41,910 --> 00:31:47,930 the heart of our energetics for how we function as human 451 00:31:47,930 --> 00:31:57,990 beings, is derived from it's crystal structure. 452 00:31:57,990 --> 00:32:01,600 But in fact, evolutionarily, it's related to 453 00:32:01,600 --> 00:32:04,360 that flagella motor. 454 00:32:04,360 --> 00:32:08,670 And as that proton comes down the gradient, or actually this 455 00:32:08,670 --> 00:32:11,470 is presented upside down, so there's the outside as it goes 456 00:32:11,470 --> 00:32:17,070 through in this direction, the ATP synthase, which is known 457 00:32:17,070 --> 00:32:29,990 as the F1F0 ATP synthase rotates. 458 00:32:29,990 --> 00:32:33,590 And probably this came first. 459 00:32:33,590 --> 00:32:35,390 It's a little hard in this one because you don't have the 460 00:32:35,390 --> 00:32:38,690 flagella, so what scientists have done is they've been able 461 00:32:38,690 --> 00:32:42,120 to attach something like an actin filament onto this F1 462 00:32:42,120 --> 00:32:47,130 ATP synthase, and show that as a proton 463 00:32:47,130 --> 00:32:49,650 passages the thing rotates. 464 00:32:49,650 --> 00:32:53,710 So in all likelihood what happened in evolution was this 465 00:32:53,710 --> 00:32:59,690 came first, and then later the machinery got duplicated and 466 00:32:59,690 --> 00:33:02,120 evolved to become a nanomotor. 467 00:33:02,120 --> 00:33:05,610 And as I told you the other day, that apparatus for the 468 00:33:05,610 --> 00:33:09,920 flagella motor got evolved again into becoming a little 469 00:33:09,920 --> 00:33:17,050 syringe that bacteria like ursinia are able to use to 470 00:33:17,050 --> 00:33:20,240 pump or to squeeze proteins or squirt proteins from inside 471 00:33:20,240 --> 00:33:25,780 them into inside of a mammalian cell. 472 00:33:25,780 --> 00:33:28,080 OK, well. 473 00:33:28,080 --> 00:33:32,460 Thanks to this work by Peter Mitchell then, we can now 474 00:33:32,460 --> 00:33:37,840 understand how cells were able to take advantage of that 475 00:33:37,840 --> 00:33:40,805 energy that was in the NADH. 476 00:33:44,680 --> 00:33:51,230 So this process is known as respiration. 477 00:33:51,230 --> 00:33:58,680 And basically it's taking the 2NADH. 478 00:34:02,060 --> 00:34:04,060 I'm supposed to see the physical therapist today, so I 479 00:34:04,060 --> 00:34:08,110 hope we're going to begin to make progress to lecturing on 480 00:34:08,110 --> 00:34:10,460 two feet sooner or later. 481 00:34:10,460 --> 00:34:19,570 Plus 2NAD+ plus two water. 482 00:34:19,570 --> 00:34:25,389 So as I said earlier, NADH and protons, 483 00:34:25,389 --> 00:34:27,909 it's basically hydrogen. 484 00:34:27,909 --> 00:34:32,090 It's the equivalent of having hydrogen gas and adding 485 00:34:32,090 --> 00:34:36,830 oxygen, and we're burning the hydrogen gas down to water. 486 00:34:36,830 --> 00:34:39,429 So there's a lot to yield water. 487 00:34:39,429 --> 00:34:42,560 So there's a lot of energy potentially can be given off. 488 00:34:42,560 --> 00:34:47,630 That's the 50 kcals per mole. 489 00:34:47,630 --> 00:34:51,730 Now if you recall when we talked about thermodynamics, 490 00:34:51,730 --> 00:35:08,660 so the NADH is up here, by the time we get down to the 2NAD+ 491 00:35:08,660 --> 00:35:11,830 plus the water, the two waters, 492 00:35:11,830 --> 00:35:13,960 energetically we're down here. 493 00:35:13,960 --> 00:35:17,930 And this is about a free energy changed of about 50 494 00:35:17,930 --> 00:35:20,990 kcals per mole. 495 00:35:20,990 --> 00:35:25,610 In physiological terms, that's a huge amount of energy. 496 00:35:25,610 --> 00:35:30,250 And I think some of the textbooks compare it to 497 00:35:30,250 --> 00:35:33,910 letting a stick of dynamite off inside of a cell. 498 00:35:33,910 --> 00:35:37,650 So it's really more than biology figured out how to 499 00:35:37,650 --> 00:35:39,780 handle this in a single step. 500 00:35:39,780 --> 00:35:41,800 But do you remember that important principle about a 501 00:35:41,800 --> 00:35:44,450 thermodynamic property, when I had the little 502 00:35:44,450 --> 00:35:45,410 picture of the skier? 503 00:35:45,410 --> 00:35:48,730 It doesn't matter which pathway you take. 504 00:35:48,730 --> 00:35:51,520 You get the same amount of energy released whether you go 505 00:35:51,520 --> 00:35:53,790 down the black diamond slope or you go 506 00:35:53,790 --> 00:35:55,420 down the bunny slope. 507 00:35:55,420 --> 00:36:01,750 So in fact, the way biology has learned, life has learned 508 00:36:01,750 --> 00:36:04,960 to control this amount of energy is basically taking the 509 00:36:04,960 --> 00:36:06,290 bunny slope. 510 00:36:06,290 --> 00:36:14,350 And so the energy drop occurs in a series of stages, where 511 00:36:14,350 --> 00:36:17,720 you have the transfer of two electrons to a lower state 512 00:36:17,720 --> 00:36:21,760 intermediate, transfer of two electrons to another one, 513 00:36:21,760 --> 00:36:25,400 transfer of two electrons to another one. 514 00:36:25,400 --> 00:36:28,560 And where this connects with the stuff that I just told 515 00:36:28,560 --> 00:36:32,800 you, is as these two electrons are coming down, what's 516 00:36:32,800 --> 00:36:38,740 happening is a proton is being pumped from the 517 00:36:38,740 --> 00:36:41,250 inside to the outside. 518 00:36:41,250 --> 00:36:47,750 As it moves to the next lower energy state, another proton 519 00:36:47,750 --> 00:36:51,860 gets pumped from the inside, the outside. 520 00:36:51,860 --> 00:36:53,590 And the same thing happens here. 521 00:36:58,300 --> 00:37:08,790 So at the end, you get the two hydrogens plus the half of an 522 00:37:08,790 --> 00:37:10,680 oxygen and we get a water molecule 523 00:37:10,680 --> 00:37:13,010 from these two electrons. 524 00:37:13,010 --> 00:37:18,890 But what's happened is these three protons have changed 525 00:37:18,890 --> 00:37:20,820 from inside to outside. 526 00:37:20,820 --> 00:37:26,500 That enables the cell to make three ATPs. 527 00:37:26,500 --> 00:37:30,740 So now instead of throwing away all that energy, losing 528 00:37:30,740 --> 00:37:33,560 the NADH as in the fermentations, the cell is 529 00:37:33,560 --> 00:37:37,940 extracting energy out of it by taking advantage of this 530 00:37:37,940 --> 00:37:42,440 principle of the proton gradient. 531 00:37:42,440 --> 00:37:45,720 So the game changes if you're this 532 00:37:45,720 --> 00:37:48,530 evolutionary designer or something. 533 00:37:48,530 --> 00:37:52,390 If you were trying to design life from first principles 534 00:37:52,390 --> 00:37:53,950 now, you could take advantage of this. 535 00:37:53,950 --> 00:37:56,350 Well of course it doesn't happen that way. 536 00:37:56,350 --> 00:38:00,620 Experiments happen all the time in nature and something 537 00:38:00,620 --> 00:38:02,940 happens and sometimes it's very efficient, 538 00:38:02,940 --> 00:38:03,860 sometimes it isn't. 539 00:38:03,860 --> 00:38:06,160 But if it's there first it gets going. 540 00:38:06,160 --> 00:38:12,440 In this case, the need now, or the opportunity was that if an 541 00:38:12,440 --> 00:38:20,505 organism could get more NADH out of that original molecule 542 00:38:20,505 --> 00:38:24,400 of glucose, it could make more energy than somebody else. 543 00:38:24,400 --> 00:38:29,950 And so the ultimate way to take a molecule of glucose is 544 00:38:29,950 --> 00:38:32,560 if you burn it with, oxygen you end up with six carbon 545 00:38:32,560 --> 00:38:33,990 dioxides and water. 546 00:38:33,990 --> 00:38:35,410 You burn it all away. 547 00:38:35,410 --> 00:38:39,590 So there's a system that, in essence, does that. 548 00:38:39,590 --> 00:38:43,130 It's known as the citric acid cycle. 549 00:38:47,230 --> 00:38:55,080 So you have the pyruvate that comes from glycolysis. 550 00:38:55,080 --> 00:39:00,680 And the way it's processed is first, one of the carboxyl 551 00:39:00,680 --> 00:39:03,620 group on the pyruvate is released, and 552 00:39:03,620 --> 00:39:05,480 this produces acetyl. 553 00:39:13,860 --> 00:39:15,610 You can look to see what CoA is. 554 00:39:15,610 --> 00:39:16,900 At the moment, it doesn't matter. 555 00:39:16,900 --> 00:39:20,830 What does matter is this is a 3-carbon compound. 556 00:39:20,830 --> 00:39:24,700 Acetyl, as you probably know, is a two-carbon compound. 557 00:39:24,700 --> 00:39:27,790 And when you look in your textbooks at the citric acid 558 00:39:27,790 --> 00:39:33,990 cycle, you'll see this very confusing circle with lots of 559 00:39:33,990 --> 00:39:38,360 compounds and enzymes and stuff. 560 00:39:38,360 --> 00:39:40,850 But I want you just keep your eye on the ball here. 561 00:39:40,850 --> 00:39:45,750 If you'll notice, the compound over here is in the cycle, is 562 00:39:45,750 --> 00:39:47,390 four carbons. 563 00:39:47,390 --> 00:39:50,480 And what happens is this 2-carbon compound that was 564 00:39:50,480 --> 00:39:55,170 derived from pyruvate gets added to this to give a 565 00:39:55,170 --> 00:39:57,080 6-carbon compound. 566 00:39:57,080 --> 00:40:01,690 And then that gets converted to a 5-carbon compound with a 567 00:40:01,690 --> 00:40:04,980 molecule of CO2 being given off. 568 00:40:04,980 --> 00:40:10,120 That in turn gets converted to a 4-carbon compound with 569 00:40:10,120 --> 00:40:13,480 another molecule of CO2 given off. 570 00:40:13,480 --> 00:40:16,400 And then there's some molecular gymnastics here that 571 00:40:16,400 --> 00:40:20,620 change the nature of the four carbon compound a bit so you 572 00:40:20,620 --> 00:40:22,940 can get back into the cycle. 573 00:40:22,940 --> 00:40:27,970 But look what's happened to those three carbons that were 574 00:40:27,970 --> 00:40:29,280 in the pyruvate. 575 00:40:29,280 --> 00:40:32,850 There's one of them, there's the other one, 576 00:40:32,850 --> 00:40:34,490 there's the other one. 577 00:40:34,490 --> 00:40:40,250 So this citric acid cycle produces, it actually makes 578 00:40:40,250 --> 00:40:45,840 some ATP, but it makes quite a bit of NADH. 579 00:40:45,840 --> 00:40:58,000 And it also makes another, one more reduced electron carrier. 580 00:40:58,000 --> 00:41:01,920 It's not NADH, it's another one that's used in the cell. 581 00:41:01,920 --> 00:41:07,160 But anyway, the cell is then able to take all of this NADH 582 00:41:07,160 --> 00:41:12,250 and this electron carrier plus these to give you, what I'd 583 00:41:12,250 --> 00:41:16,430 said, the net yield you get from respiration. 584 00:41:16,430 --> 00:41:25,330 36 ATPs from a single molecule of glucose. 585 00:41:25,330 --> 00:41:29,205 So sort of quite remarkable to some extent. 586 00:41:29,205 --> 00:41:32,960 We're looking at evolution, through, if you will, almost 587 00:41:32,960 --> 00:41:36,770 like looking at biochemical fossils and then when 588 00:41:36,770 --> 00:41:41,060 something works, it's a living fossil, we still 589 00:41:41,060 --> 00:41:43,550 find it in our cells.