1 00:00:13,990 --> 00:00:18,100 HAZEL SIVE: Let's move on with Biochemistry III. 2 00:00:18,100 --> 00:00:23,620 And we have, as you recall, being exploring the 3 00:00:23,620 --> 00:00:26,090 fascinating and complicated set of 4 00:00:26,090 --> 00:00:28,930 macromolecules inside a cell-- 5 00:00:28,930 --> 00:00:33,320 inside the cell that we're using, in a way, analogous to 6 00:00:33,320 --> 00:00:38,100 a factory that is a production line for synthesis of various 7 00:00:38,100 --> 00:00:41,680 components that are required for function of the cell, for 8 00:00:41,680 --> 00:00:46,580 its replication, and for perpetuation of the organism. 9 00:00:46,580 --> 00:00:50,310 Today I want to talk to you about some parameters that 10 00:00:50,310 --> 00:00:52,693 surround the chemical reactions of biochemistry. 11 00:01:07,920 --> 00:01:15,110 We'll talk briefly about thermodynamics and energy 12 00:01:15,110 --> 00:01:17,160 considerations. 13 00:01:17,160 --> 00:01:21,350 And then I want to introduce you to a huge and pivotal 14 00:01:21,350 --> 00:01:24,750 class of proteins, the enzymes. 15 00:01:24,750 --> 00:01:28,400 And then we'll talk very briefly about the currency of 16 00:01:28,400 --> 00:01:30,530 energy in the cell. 17 00:01:35,940 --> 00:01:40,350 Let's start with thermodynamics, which we will 18 00:01:40,350 --> 00:01:44,870 define as the rules underlying energy 19 00:01:44,870 --> 00:01:47,020 usage in chemical reactions. 20 00:01:59,450 --> 00:02:02,310 Rules underlying energy use. 21 00:02:08,520 --> 00:02:11,410 And really, it's the first law of thermodynamics that we're 22 00:02:11,410 --> 00:02:12,250 interested in. 23 00:02:12,250 --> 00:02:18,160 We're interested in the fact that energy is neither created 24 00:02:18,160 --> 00:02:23,740 nor destroyed, that it is converted from one form to 25 00:02:23,740 --> 00:02:28,220 another and that there is conservation of energy. 26 00:02:32,990 --> 00:02:36,840 And the other laws are embedded in what we'll talk, 27 00:02:36,840 --> 00:02:38,860 but these are the ones that are really important for 28 00:02:38,860 --> 00:02:40,110 biochemistry. 29 00:02:44,290 --> 00:02:49,120 Let's think about a basic chemical reaction, some kind 30 00:02:49,120 --> 00:02:50,370 of substrate. 31 00:02:54,570 --> 00:02:57,660 That's a biological term which we'll use. 32 00:02:57,660 --> 00:03:03,180 It's equivalent to the term "reactant." And I could use R, 33 00:03:03,180 --> 00:03:05,890 but I'm going to use S, because that's what we'll use 34 00:03:05,890 --> 00:03:08,950 in biochemistry, in life. 35 00:03:08,950 --> 00:03:11,280 And that gives rise to a product. 36 00:03:15,520 --> 00:03:19,610 And chemical reactions can go in both directions. 37 00:03:19,610 --> 00:03:25,690 One reaction may predominate over the other. 38 00:03:25,690 --> 00:03:27,810 But the reaction is reversible. 39 00:03:27,810 --> 00:03:31,220 And the questions that we're going to ask is, does a 40 00:03:31,220 --> 00:03:41,110 chemical reaction require or release energy? 41 00:03:52,360 --> 00:03:54,640 How fast does the reaction go-- 42 00:04:02,100 --> 00:04:05,410 which is referred to as the rate of the reaction. 43 00:04:05,410 --> 00:04:15,180 And how far, which refers to the equilibrium point. 44 00:04:15,180 --> 00:04:23,690 Equilibrium, where equilibrium is defined as the place where 45 00:04:23,690 --> 00:04:26,940 the forward rate and the back rate are equal. 46 00:04:40,350 --> 00:04:42,970 And at equilibrium, even though the forward and the 47 00:04:42,970 --> 00:04:46,500 back rate are equal, it's not that you have equal amounts of 48 00:04:46,500 --> 00:04:50,580 substrate and product, you have a particular ratio of 49 00:04:50,580 --> 00:04:53,980 substrate to product that is characteristic for the 50 00:04:53,980 --> 00:04:55,990 chemical reaction. 51 00:04:55,990 --> 00:05:03,320 So you get a specific substrate or reactant to 52 00:05:03,320 --> 00:05:07,100 product ratio. 53 00:05:07,100 --> 00:05:11,290 Let's make this S a little larger, to match 54 00:05:11,290 --> 00:05:13,700 the P. There we go. 55 00:05:13,700 --> 00:05:16,310 Good. 56 00:05:16,310 --> 00:05:22,700 The thing that you need to know is called Gibbs free 57 00:05:22,700 --> 00:05:29,440 energy and the change in Gibbs free energy with a reaction. 58 00:05:29,440 --> 00:05:34,500 So in any chemical reaction, there are a couple of kinds of 59 00:05:34,500 --> 00:05:36,580 energy considerations. 60 00:05:36,580 --> 00:05:41,100 The one important for us is G, the Gibbs free energy, which 61 00:05:41,100 --> 00:05:49,650 is the usable or, the convention is, free energy. 62 00:05:49,650 --> 00:05:52,580 The other term you need is H, which is the 63 00:05:52,580 --> 00:05:55,940 total energy, or enthalpy. 64 00:05:59,940 --> 00:06:03,655 Entropy, S, the unusable energy. 65 00:06:07,580 --> 00:06:13,290 And you also need T, which is the temperature in absolute 66 00:06:13,290 --> 00:06:15,510 degrees Kelvin. 67 00:06:15,510 --> 00:06:17,870 And the reaction that you may be familiar with or the 68 00:06:17,870 --> 00:06:24,090 equation you may be familiar with is delta G equals delta H 69 00:06:24,090 --> 00:06:30,020 minus T delta S. And the thing that's important here is what 70 00:06:30,020 --> 00:06:31,390 this means. 71 00:06:31,390 --> 00:06:38,000 Delta G is the change in free energy 72 00:06:38,000 --> 00:06:39,365 with a chemical reaction. 73 00:06:48,710 --> 00:06:53,770 And every chemical reaction has a characteristic change in 74 00:06:53,770 --> 00:06:55,210 free energy. 75 00:06:55,210 --> 00:06:59,350 And depending on what that is, one can say certain things 76 00:06:59,350 --> 00:07:03,640 about how likely the reaction is to proceed. 77 00:07:03,640 --> 00:07:10,260 If delta G is negative for a particular chemical reaction, 78 00:07:10,260 --> 00:07:20,710 then as the reaction proceeds, energy is released, the 79 00:07:20,710 --> 00:07:27,460 reaction is termed exergonic, and it is sometimes 80 00:07:27,460 --> 00:07:29,810 "spontaneous." I'm going to put that in quotes. 81 00:07:29,810 --> 00:07:31,060 You'll see why in a moment. 82 00:07:34,460 --> 00:07:37,085 The flip is true if delta G is positive. 83 00:07:42,480 --> 00:07:49,990 This means that the reaction requires energy in order to 84 00:07:49,990 --> 00:07:56,640 proceed, and it is referred to as endergonic. 85 00:08:01,510 --> 00:08:04,770 And if delta G is 0, the reaction is at equilibrium. 86 00:08:28,650 --> 00:08:32,120 The notion that's quite useful to think about this is balls 87 00:08:32,120 --> 00:08:34,400 rolling up and down hills. 88 00:08:34,400 --> 00:08:38,390 For a reaction that is exergonic, a ball rolling down 89 00:08:38,390 --> 00:08:43,280 a hill will decrease its delta G. It will release energy as 90 00:08:43,280 --> 00:08:44,830 it rolls down the hill. 91 00:08:44,830 --> 00:08:46,590 And you can actually plot this. 92 00:08:46,590 --> 00:08:49,850 And you'll see lots of plots like this where, if you plot 93 00:08:49,850 --> 00:08:53,090 energy over the course of the reaction, you will see that 94 00:08:53,090 --> 00:08:55,220 the reactants start off at a higher 95 00:08:55,220 --> 00:08:56,820 energy than the products. 96 00:08:56,820 --> 00:08:59,300 And as they are rolling down the hill, 97 00:08:59,300 --> 00:09:00,930 there is energy released. 98 00:09:00,930 --> 00:09:04,060 And the flip is true for an endergonic reaction where 99 00:09:04,060 --> 00:09:05,600 delta G is positive. 100 00:09:05,600 --> 00:09:09,070 You have to put in energy to get the product out. 101 00:09:15,650 --> 00:09:16,670 Now-- 102 00:09:16,670 --> 00:09:19,540 and this is where it gets interesting. 103 00:09:19,540 --> 00:09:22,860 And this is where we get back to "spontaneous" in quotes-- 104 00:09:22,860 --> 00:09:26,800 chemical reactions can be exergonic, but they may not 105 00:09:26,800 --> 00:09:28,850 proceed spontaneously. 106 00:09:28,850 --> 00:09:34,330 If you imagine a ball sitting at the top of a hill, if the 107 00:09:34,330 --> 00:09:38,440 ball is sitting right on the slope of a hill, and you let 108 00:09:38,440 --> 00:09:42,550 the ball go, it'll go zipping down the hill, right? 109 00:09:42,550 --> 00:09:45,710 But if the ball is sitting on the top of the hill, but it's 110 00:09:45,710 --> 00:09:48,720 in a little hollow, it's not going to go anywhere unless 111 00:09:48,720 --> 00:09:51,030 you give a push. 112 00:09:51,030 --> 00:09:52,230 That's very important. 113 00:09:52,230 --> 00:09:55,310 And that kind of notion is embodied in chemical 114 00:09:55,310 --> 00:09:56,460 principles. 115 00:09:56,460 --> 00:09:58,220 So let's write this out. 116 00:09:58,220 --> 00:10:00,400 And then we'll formalize this. 117 00:10:00,400 --> 00:10:10,805 Delta G can be negative, but a reaction does not proceed. 118 00:10:22,170 --> 00:10:27,780 And that's because you've got to get the reactants out of 119 00:10:27,780 --> 00:10:31,310 that little hollow at the top of the hill. 120 00:10:31,310 --> 00:10:34,300 And in order to get the reactants out of the little 121 00:10:34,300 --> 00:10:36,740 hollow at the top of the hill, you need something called 122 00:10:36,740 --> 00:10:37,990 activation energy. 123 00:10:40,810 --> 00:10:47,360 Activation energy is required. 124 00:10:47,360 --> 00:10:51,780 I'm going to abbreviate that AC. 125 00:10:54,606 --> 00:10:58,836 You can abbreviate it whatever you like. 126 00:10:58,836 --> 00:11:02,560 And the thing about chemical reactions that makes them 127 00:11:02,560 --> 00:11:06,840 proceed in chemistry and makes them proceed in biochemistry, 128 00:11:06,840 --> 00:11:10,890 in life, is that you need something to overcome that 129 00:11:10,890 --> 00:11:12,560 activation energy. 130 00:11:12,560 --> 00:11:14,180 Back to the ball analogy-- 131 00:11:14,180 --> 00:11:16,580 I think of this because I have a dog. 132 00:11:16,580 --> 00:11:17,400 His name is Archer. 133 00:11:17,400 --> 00:11:18,920 He's a black Labrador-- 134 00:11:18,920 --> 00:11:20,290 in case you're interested-- 135 00:11:20,290 --> 00:11:24,240 and he's very fond of balls. 136 00:11:24,240 --> 00:11:27,500 And they sit at the top of the hill in my yard. 137 00:11:27,500 --> 00:11:29,900 And there's a whole line of them . 138 00:11:29,900 --> 00:11:33,100 And they will sit there forever unless Archer either 139 00:11:33,100 --> 00:11:35,890 intelligently or by mistake pushes one. 140 00:11:35,890 --> 00:11:38,270 And then it goes rolling down the hill, and he can get it. 141 00:11:38,270 --> 00:11:41,860 So you have to do something to start the reaction. 142 00:11:41,860 --> 00:11:44,450 You have to give energy. 143 00:11:44,450 --> 00:11:46,000 Where does that energy come from? 144 00:11:46,000 --> 00:11:48,030 Well, it comes from somewhere. 145 00:11:48,030 --> 00:11:52,090 And you can decrease that activation energy and really 146 00:11:52,090 --> 00:11:56,160 get a reaction to proceed quickly by the use of 147 00:11:56,160 --> 00:12:00,070 chemicals called catalysts. 148 00:12:00,070 --> 00:12:12,640 So catalysts decrease activation energy and allow a 149 00:12:12,640 --> 00:12:15,460 reaction to proceed. 150 00:12:15,460 --> 00:12:27,230 Catalysts do not change delta G of the whole reaction or the 151 00:12:27,230 --> 00:12:28,495 equilibrium point. 152 00:12:35,130 --> 00:12:36,800 So you're not going to get more. 153 00:12:36,800 --> 00:12:38,930 You're not going to really change the reaction. 154 00:12:38,930 --> 00:12:42,140 You're just going to get it to go. 155 00:12:42,140 --> 00:12:52,460 Catalysts do increase the rate of reaction. 156 00:12:52,460 --> 00:12:53,710 That's the point. 157 00:12:57,970 --> 00:13:01,910 And they do this, as we'll explore, by promoting 158 00:13:01,910 --> 00:13:05,470 something called a transition state, which is a high-energy 159 00:13:05,470 --> 00:13:07,640 form of the reactants. 160 00:13:07,640 --> 00:13:11,310 If we go back to our ball analogy, if you kick the ball 161 00:13:11,310 --> 00:13:15,120 so that it comes up out of the hollow, that kick that you 162 00:13:15,120 --> 00:13:18,370 give the ball, the energy you put in there, is going to get 163 00:13:18,370 --> 00:13:20,040 the ball rolling down the hill, and the 164 00:13:20,040 --> 00:13:21,600 reaction will proceed. 165 00:13:21,600 --> 00:13:37,720 So catalysts promote a transition state, which is a 166 00:13:37,720 --> 00:13:46,065 high-energy form of the reactants. 167 00:13:53,830 --> 00:13:56,170 Let's look at a couple of slides that I drew for you. 168 00:13:56,170 --> 00:14:01,690 So here is a blank chart. 169 00:14:01,690 --> 00:14:05,080 And I've got delta G on the y-axis and the reaction course 170 00:14:05,080 --> 00:14:07,510 on the x-axis. 171 00:14:07,510 --> 00:14:09,110 And here's a reaction curve. 172 00:14:11,670 --> 00:14:15,000 The reaction overall is going to have a delta G that's 173 00:14:15,000 --> 00:14:18,650 negative because you see that the products are at the bottom 174 00:14:18,650 --> 00:14:21,470 of the hill, relative to the reactants. 175 00:14:21,470 --> 00:14:25,320 But there's also this hump that they have to get over. 176 00:14:25,320 --> 00:14:28,285 And that is what requires activation energy. 177 00:14:33,560 --> 00:14:37,690 In an uncatalyzed reaction or a catalyzed reaction, you have 178 00:14:37,690 --> 00:14:39,900 to go through this high-energy state. 179 00:14:39,900 --> 00:14:42,860 So here is a catalyzed reaction that I put on as 180 00:14:42,860 --> 00:14:45,630 blue, the uncatalyzed as red. 181 00:14:45,630 --> 00:14:49,130 And you can see what happens to the little hill that has to 182 00:14:49,130 --> 00:14:52,090 be climbed before the reaction can proceed. 183 00:14:52,090 --> 00:14:55,970 The amount of energy you need to move that chemical reaction 184 00:14:55,970 --> 00:15:00,820 decreases relative to the uncatalyzed reaction. 185 00:15:00,820 --> 00:15:04,830 So you decrease the little hollow in which the ball is 186 00:15:04,830 --> 00:15:07,470 sitting, in order to get the reaction to proceed. 187 00:15:07,470 --> 00:15:11,700 But at the end, you'll end up with exactly the same reaction 188 00:15:11,700 --> 00:15:14,065 as you would have if it were not catalyzed. 189 00:15:17,910 --> 00:15:19,260 All right. 190 00:15:19,260 --> 00:15:22,090 What does this have to do with biology? 191 00:15:22,090 --> 00:15:23,450 Well, it has everything. 192 00:15:23,450 --> 00:15:26,510 Because there's a class of proteins that we'll talk about 193 00:15:26,510 --> 00:15:30,720 for the rest of the lecture that are biological catalysts. 194 00:15:30,720 --> 00:15:32,885 And without them, there would be no life. 195 00:15:35,550 --> 00:15:41,090 So number two, we'll talk about enzymes. 196 00:15:41,090 --> 00:15:46,565 And enzymes are biological catalysts. 197 00:15:53,290 --> 00:15:54,900 They are usually protein. 198 00:15:57,860 --> 00:16:02,060 And all of the ones that we'll talk about are proteins. 199 00:16:02,060 --> 00:16:07,410 But they can also be RNA. 200 00:16:07,410 --> 00:16:10,270 And a Nobel Prize was given some years ago for the 201 00:16:10,270 --> 00:16:14,050 discovery of RNA enzymes that are catalysts. 202 00:16:14,050 --> 00:16:17,940 And Dr. Sinha has posted on the website a video of the 203 00:16:17,940 --> 00:16:21,190 Nobel lecture of Professor Sidney Altman, who got the 204 00:16:21,190 --> 00:16:25,180 Nobel Prize for the discovery of RNAs as enzymes. 205 00:16:25,180 --> 00:16:28,280 But we're going to focus on proteins. 206 00:16:28,280 --> 00:16:31,250 We're going to rewrite the chemical reaction that I have 207 00:16:31,250 --> 00:16:34,380 on that board in a slightly different way, which is the 208 00:16:34,380 --> 00:16:38,690 conventional way for thinking about enzymes, where we're 209 00:16:38,690 --> 00:16:48,250 going to have an enzyme, abbreviated E, plus the 210 00:16:48,250 --> 00:16:51,510 substrate that is going to form an 211 00:16:51,510 --> 00:16:54,020 enzyme-substrate complex. 212 00:16:54,020 --> 00:16:58,080 And this is the transition state, so called 213 00:16:58,080 --> 00:16:59,696 transition-state complex. 214 00:17:05,810 --> 00:17:09,190 And that, as I'll draw in a moment, is going to give rise 215 00:17:09,190 --> 00:17:11,680 to the enzyme plus the product. 216 00:17:11,680 --> 00:17:13,560 So let me just draw this up there. 217 00:17:13,560 --> 00:17:15,050 And then we'll talk about what these mean. 218 00:17:15,050 --> 00:17:23,290 E is enzyme, S is substrate, as previously. 219 00:17:23,290 --> 00:17:29,790 This enzyme substrate, ES, is the transition-state complex. 220 00:17:39,420 --> 00:17:42,850 And what it is in biological terms is some kind of 221 00:17:42,850 --> 00:17:46,850 high-energy state of the substrate that is linked to 222 00:17:46,850 --> 00:17:48,100 the enzyme. 223 00:17:50,570 --> 00:18:02,060 So it's a high-energy substrate 224 00:18:02,060 --> 00:18:03,310 linked to the enzyme. 225 00:18:11,410 --> 00:18:15,250 This transition-state complex then resolves to release the 226 00:18:15,250 --> 00:18:17,460 enzyme, which can be used again. 227 00:18:17,460 --> 00:18:21,030 As in the case of all catalysts, they can be reused 228 00:18:21,030 --> 00:18:24,415 to give rise to the enzyme and the product. 229 00:18:30,670 --> 00:18:33,352 So why is this interesting? 230 00:18:33,352 --> 00:18:34,602 It's fascinating because -- 231 00:18:37,290 --> 00:18:41,120 Actually, let me before I tell you why it's so fascinating, 232 00:18:41,120 --> 00:18:42,370 let me show you something. 233 00:18:42,370 --> 00:18:45,290 So I drew this for you. 234 00:18:45,290 --> 00:18:51,370 Here is a representation of an enzyme and something I'll 235 00:18:51,370 --> 00:18:54,090 explore on the board in a moment called the active site, 236 00:18:54,090 --> 00:18:58,380 where the substrate fits into the enzyme. 237 00:18:58,380 --> 00:19:01,830 Here is an enzyme-substrate complex, a high-energy 238 00:19:01,830 --> 00:19:07,760 transition-state complex, that undergoes reaction, catalysis, 239 00:19:07,760 --> 00:19:09,760 to give rise to the product. 240 00:19:09,760 --> 00:19:12,050 The product is released, and you start 241 00:19:12,050 --> 00:19:13,460 the whole thing again. 242 00:19:15,990 --> 00:19:19,160 The thing about biological catalysts that are really 243 00:19:19,160 --> 00:19:21,700 different from chemical catalysts is their 244 00:19:21,700 --> 00:19:23,190 specificity. 245 00:19:23,190 --> 00:19:26,640 Now, you may have heard of platinum as a catalyst. 246 00:19:26,640 --> 00:19:29,900 Platinum is an incredibly powerful catalyst that 247 00:19:29,900 --> 00:19:32,220 promotes almost any chemical reaction 248 00:19:32,220 --> 00:19:35,270 that involves hydrogen-- 249 00:19:35,270 --> 00:19:38,870 but any chemical reaction. 250 00:19:38,870 --> 00:19:42,260 The difference between platinum and enzymes is that 251 00:19:42,260 --> 00:19:45,870 enzymes are incredibly specific for a particular 252 00:19:45,870 --> 00:19:49,270 chemical reaction. 253 00:19:49,270 --> 00:19:51,530 Let's write that. 254 00:19:51,530 --> 00:20:06,130 Enzymes are highly specific, exquisitely specific, for the 255 00:20:06,130 --> 00:20:07,380 particular reaction. 256 00:20:12,020 --> 00:20:15,270 And they maintain this specificity by fitting the 257 00:20:15,270 --> 00:20:18,890 substrate into what I've got on the screen there, the 258 00:20:18,890 --> 00:20:22,230 active site, which is a particular part of the enzyme, 259 00:20:22,230 --> 00:20:25,890 a particular part of the protein. 260 00:20:25,890 --> 00:20:35,250 And the deal is that the substrate fits into a part of 261 00:20:35,250 --> 00:20:38,240 the protein called the active site. 262 00:20:41,180 --> 00:20:45,830 The active site is a very small part of the protein. 263 00:20:45,830 --> 00:20:50,110 And it's this interaction with the protein and the active 264 00:20:50,110 --> 00:20:54,545 site that promotes the transition state. 265 00:21:04,250 --> 00:21:06,610 How does it promote the transition state? 266 00:21:06,610 --> 00:21:11,610 Well, you can think physically it might change the shape of 267 00:21:11,610 --> 00:21:14,180 the substrate to make it higher energy. 268 00:21:14,180 --> 00:21:16,440 You could imagine it adds charge. 269 00:21:16,440 --> 00:21:20,600 You could imagine it adds particular orientation between 270 00:21:20,600 --> 00:21:23,540 two substrate molecules that happen to be 271 00:21:23,540 --> 00:21:24,600 in the active site. 272 00:21:24,600 --> 00:21:28,560 Or it might align the substrate in the correct way. 273 00:21:28,560 --> 00:21:33,420 So we can actually say that the substrate is promoted to 274 00:21:33,420 --> 00:21:39,920 undergo catalysis by controlling-- 275 00:21:39,920 --> 00:21:42,940 let's just list these-- 276 00:21:42,940 --> 00:21:47,550 orientation of the substrate in the access site, adding 277 00:21:47,550 --> 00:21:53,520 strain to the substrate, or possibly adding a particular 278 00:21:53,520 --> 00:21:55,700 charge to the substrate. 279 00:22:00,090 --> 00:22:02,640 Let's look through a couple of things here. 280 00:22:02,640 --> 00:22:03,780 Okay, this is from your book. 281 00:22:03,780 --> 00:22:05,330 Let's not dwell on that. 282 00:22:05,330 --> 00:22:09,780 Let's go to this one, which is not quite-- 283 00:22:09,780 --> 00:22:11,560 Ah, it's on that screen. 284 00:22:11,560 --> 00:22:13,400 Good. 285 00:22:13,400 --> 00:22:17,010 This is an example of enzyme specificity that you see every 286 00:22:17,010 --> 00:22:18,680 day, probably. 287 00:22:18,680 --> 00:22:21,570 On Diet Coke, it says, "warning, fennel 288 00:22:21,570 --> 00:22:23,440 phenylketonurics, contains 289 00:22:23,440 --> 00:22:26,640 phenylalanine." What's the deal? 290 00:22:26,640 --> 00:22:31,480 There is a disorder called phenylketonuria where people 291 00:22:31,480 --> 00:22:37,220 are unable to digest the amino acid phenylalanine. 292 00:22:37,220 --> 00:22:40,730 This is an essential amino acid, but too 293 00:22:40,730 --> 00:22:42,420 much of it is bad. 294 00:22:42,420 --> 00:22:46,820 Normally when you eat phenylalanine, you use some of 295 00:22:46,820 --> 00:22:47,970 it to build proteins. 296 00:22:47,970 --> 00:22:49,070 That's good. 297 00:22:49,070 --> 00:22:52,070 But then you convert a bunch of it, using this enzyme 298 00:22:52,070 --> 00:22:55,990 called phenylalanine hydroxylase, into tyrosine, 299 00:22:55,990 --> 00:22:58,660 which you may remember is another amino acid. 300 00:22:58,660 --> 00:22:59,730 And then you use tyrosine. 301 00:22:59,730 --> 00:23:03,130 And tyrosine goes on to do a bunch of other things. 302 00:23:03,130 --> 00:23:08,090 If this enzyme is absent, then you get a side product whereby 303 00:23:08,090 --> 00:23:10,830 the excess phenylalanine makes this stuff called 304 00:23:10,830 --> 00:23:12,770 phenylpyruvic acid. 305 00:23:12,770 --> 00:23:14,620 And that is a neurotoxin. 306 00:23:14,620 --> 00:23:18,160 And it poisons the nervous system, and people have very 307 00:23:18,160 --> 00:23:21,150 severe symptoms. 308 00:23:21,150 --> 00:23:25,690 People with phenylketonuria generally have a single amino 309 00:23:25,690 --> 00:23:29,790 acid change in an enzyme that is more than 1,000 amino 310 00:23:29,790 --> 00:23:32,390 acids, where there's an arginine that has being 311 00:23:32,390 --> 00:23:34,850 changed to a tryptophan. 312 00:23:34,850 --> 00:23:37,930 And the single amino acid change lies 313 00:23:37,930 --> 00:23:39,620 in the active site. 314 00:23:39,620 --> 00:23:43,600 It stops the phenylalanine from binding the active site. 315 00:23:43,600 --> 00:23:48,480 And it leads to this really debilitating disorder. 316 00:23:48,480 --> 00:23:52,770 And so that's an everyday example of a single tiny 317 00:23:52,770 --> 00:23:58,180 change that reflects the specificity of 318 00:23:58,180 --> 00:23:59,430 the particular enzyme. 319 00:24:06,040 --> 00:24:09,520 But here's a puzzle. 320 00:24:09,520 --> 00:24:13,210 This is a space-filling model of an enzyme, 321 00:24:13,210 --> 00:24:15,200 taken from your book. 322 00:24:15,200 --> 00:24:17,730 Here's a substrate in red. 323 00:24:17,730 --> 00:24:20,930 And you can see that this enzyme has 3D shape. 324 00:24:20,930 --> 00:24:25,210 Each of these bubbles is part of one of the amino acids. 325 00:24:25,210 --> 00:24:27,900 That's what a space-filling model is. 326 00:24:27,900 --> 00:24:30,980 And the substrate fits into this active site. 327 00:24:30,980 --> 00:24:33,590 I think this is called hexokinase. 328 00:24:33,590 --> 00:24:36,120 And you can see as the substrate enters the active 329 00:24:36,120 --> 00:24:38,310 site, actually the protein changes shape. 330 00:24:38,310 --> 00:24:41,630 And it kind of closes up and contains the substrate in the 331 00:24:41,630 --> 00:24:42,410 active site. 332 00:24:42,410 --> 00:24:46,100 And catalysis takes place. 333 00:24:46,100 --> 00:24:49,130 But the active site is tiny. 334 00:24:49,130 --> 00:24:52,630 And there's this huge rest of the protein. 335 00:24:52,630 --> 00:24:54,940 And you can't get rid of the rest of the protein. 336 00:24:54,940 --> 00:24:57,920 The enzyme doesn't function if you do. 337 00:24:57,920 --> 00:25:01,680 So there's a fundamental question that we need to ask, 338 00:25:01,680 --> 00:25:05,820 which is, what do the rest of proteins do, the part outside 339 00:25:05,820 --> 00:25:07,070 the active site? 340 00:25:09,930 --> 00:25:11,180 So let's ask that question. 341 00:25:21,070 --> 00:25:34,750 What does the rest of the protein, which is large, do? 342 00:25:34,750 --> 00:25:37,960 And by the rest of the protein, I mean "not the 343 00:25:37,960 --> 00:25:45,880 active site," which is the place where the transition 344 00:25:45,880 --> 00:25:47,900 state complex is promoted. 345 00:25:50,870 --> 00:25:55,220 What it does is to regulate the activity of the enzyme. 346 00:25:55,220 --> 00:25:59,270 So the answer we can give is that it regulates, or 347 00:25:59,270 --> 00:26:01,945 controls, activity of the enzyme. 348 00:26:08,710 --> 00:26:09,460 What do I mean? 349 00:26:09,460 --> 00:26:13,060 Well, if you go back to this notion of the cell as a 350 00:26:13,060 --> 00:26:17,840 factory and enzymes as the wheels and the machines that 351 00:26:17,840 --> 00:26:20,740 get things done so that you get particular components 352 00:26:20,740 --> 00:26:25,415 synthesized, then you really want to make sure that you 353 00:26:25,415 --> 00:26:28,860 have got your production line working at the right pace. 354 00:26:28,860 --> 00:26:32,860 If you need more product, you need to speed up. 355 00:26:32,860 --> 00:26:35,910 If you need less product, you need to slow down. 356 00:26:35,910 --> 00:26:40,030 The enzymes are a place where you control how much product 357 00:26:40,030 --> 00:26:43,360 is being made, how much reactant is being used, how 358 00:26:43,360 --> 00:26:46,500 much substrate is being used. 359 00:26:46,500 --> 00:26:49,250 So the rest of the protein controls the 360 00:26:49,250 --> 00:26:51,750 activity of the enzyme. 361 00:26:51,750 --> 00:26:55,010 And there are a couple of ways that this activity is 362 00:26:55,010 --> 00:26:56,380 controlled. 363 00:26:56,380 --> 00:27:04,500 The end result is that all of these regulations affect the 364 00:27:04,500 --> 00:27:11,260 active site, even if they happen far, far away. 365 00:27:11,260 --> 00:27:15,000 And so you can imagine that if you are all lined up in a 366 00:27:15,000 --> 00:27:18,700 line, and the active site was right at the front of the line 367 00:27:18,700 --> 00:27:22,250 of you that was the enzyme prototype, and I pushed you, 368 00:27:22,250 --> 00:27:25,860 and you all fell down, the active site, the very front of 369 00:27:25,860 --> 00:27:28,460 the line, would eventually be affected although I'd pushed 370 00:27:28,460 --> 00:27:31,020 the back of the line. 371 00:27:31,020 --> 00:27:33,970 It's a silly example, but it gives you a sense of how you 372 00:27:33,970 --> 00:27:37,160 can change one thing and it has an effect far away. 373 00:27:40,100 --> 00:27:43,930 And the way that this is done is through the use of 374 00:27:43,930 --> 00:27:46,170 inhibitors. 375 00:27:46,170 --> 00:27:49,440 I'll go through some slides in a moment. 376 00:27:49,440 --> 00:27:52,030 And there are two kinds of inhibitors. 377 00:27:52,030 --> 00:27:55,790 There are reversible inhibitors, and there are 378 00:27:55,790 --> 00:27:57,050 irreversible inhibitors. 379 00:28:06,050 --> 00:28:09,570 These inhibitors may be competitive inhibitors. 380 00:28:14,580 --> 00:28:19,170 If they are competitive, they actually will bind to the 381 00:28:19,170 --> 00:28:24,930 active site as opposed to the rest of the protein. 382 00:28:24,930 --> 00:28:34,470 But if they are all of a class that is non-competitive, they 383 00:28:34,470 --> 00:28:37,325 will bind to the protein elsewhere. 384 00:28:42,150 --> 00:28:43,610 I'll show you a slide in a minute. 385 00:28:43,610 --> 00:28:45,370 But let's finish doing some board work 386 00:28:45,370 --> 00:28:47,700 here before I do that. 387 00:28:47,700 --> 00:28:50,920 There is also a very important and interesting class of 388 00:28:50,920 --> 00:28:53,750 enzyme regulators called allosteric regulators. 389 00:28:56,820 --> 00:29:04,210 There are both allosteric activators of enzyme function 390 00:29:04,210 --> 00:29:11,250 or inhibitors, things that will increase or decrease the 391 00:29:11,250 --> 00:29:13,040 rate of the reaction. 392 00:29:13,040 --> 00:29:16,540 And these allosteric activators or inhibitors will 393 00:29:16,540 --> 00:29:22,170 bind to a particular site that's not the active site. 394 00:29:25,670 --> 00:29:27,380 It's called an allosteric site-- 395 00:29:31,560 --> 00:29:36,060 not the active site, but another particular place on 396 00:29:36,060 --> 00:29:37,310 the enzyme. 397 00:29:39,160 --> 00:29:41,840 Other things that can change enzyme function-- 398 00:29:41,840 --> 00:29:45,690 pH, the enzymes that work in your stomach to digest your 399 00:29:45,690 --> 00:29:47,750 food work at a pH of 2. 400 00:29:47,750 --> 00:29:49,310 That's the pH in your stomach. 401 00:29:49,310 --> 00:29:50,730 It's very acid. 402 00:29:50,730 --> 00:29:54,930 Those enzymes will not work in your small intestine, which is 403 00:29:54,930 --> 00:29:57,430 at a pH of about 6 or 7. 404 00:29:57,430 --> 00:30:02,940 So pH, physiologically, can affect how enzymes work. 405 00:30:02,940 --> 00:30:10,680 Temperature affects how enzymes work. 406 00:30:10,680 --> 00:30:15,100 And all of these things are somehow changing the structure 407 00:30:15,100 --> 00:30:16,440 of the protein. 408 00:30:16,440 --> 00:30:19,260 And changing the structure of the protein is 409 00:30:19,260 --> 00:30:20,520 changing its function. 410 00:30:20,520 --> 00:30:24,090 We'll explore this in more specifics as the semester goes 411 00:30:24,090 --> 00:30:27,390 by, but this is what you need to understand now. 412 00:30:27,390 --> 00:30:33,710 There are also classes of molecules called cofactors, 413 00:30:33,710 --> 00:30:39,685 coenzymes, and prosthetic groups. 414 00:30:47,140 --> 00:30:49,270 I'll go through one of these in a moment. 415 00:30:49,270 --> 00:30:54,750 But all of these things have the outcome-- 416 00:30:54,750 --> 00:31:06,320 all change the structure of the protein so they'll change 417 00:31:06,320 --> 00:31:07,570 enzyme structure. 418 00:31:13,620 --> 00:31:18,115 And with that, they will change enzyme function. 419 00:31:27,590 --> 00:31:29,900 So all of these things-- 420 00:31:29,900 --> 00:31:31,550 I'm going to put it in a box-- 421 00:31:31,550 --> 00:31:34,370 change the structure of the protein. 422 00:31:34,370 --> 00:31:37,450 They will change the structure of the enzyme, 423 00:31:37,450 --> 00:31:38,830 of the active site. 424 00:31:38,830 --> 00:31:40,690 And they will change its function. 425 00:31:40,690 --> 00:31:43,220 And they're very complicated to think about. 426 00:31:43,220 --> 00:31:46,445 Let's go through some slides that will help us with this. 427 00:31:51,260 --> 00:31:53,920 Here's the notion of a competitive inhibitor. 428 00:31:53,920 --> 00:31:56,750 Here's the substrate and an active site. 429 00:31:56,750 --> 00:31:58,050 And here's an inhibitor. 430 00:31:58,050 --> 00:32:00,820 And you can see I've drawn it so that it kind of looks like 431 00:32:00,820 --> 00:32:03,990 a substrate, but it's got some extra stuff. 432 00:32:03,990 --> 00:32:07,530 And so when it binds to the active site, it binds 433 00:32:07,530 --> 00:32:08,960 specifically. 434 00:32:08,960 --> 00:32:11,250 But it's not actually a substrate, because it's got 435 00:32:11,250 --> 00:32:14,490 this extra chemical moiety which does not make it 436 00:32:14,490 --> 00:32:16,270 available for catalysis. 437 00:32:16,270 --> 00:32:19,480 And that stops the enzyme. 438 00:32:19,480 --> 00:32:23,770 That competitive inhibitor may or may not be able to come off 439 00:32:23,770 --> 00:32:25,970 the enzyme and allow it to work again. 440 00:32:25,970 --> 00:32:28,180 It depends on the inhibitor. 441 00:32:28,180 --> 00:32:31,480 Here's another one, a noncompetitive inhibitor that 442 00:32:31,480 --> 00:32:35,080 doesn't look like a substrate and binds somewhere else on 443 00:32:35,080 --> 00:32:38,450 the enzyme and, in doing so, changes the shape of the 444 00:32:38,450 --> 00:32:39,800 active site. 445 00:32:39,800 --> 00:32:42,730 So the active site now can't bind the substrate anymore 446 00:32:42,730 --> 00:32:44,260 because its shape has being changed. 447 00:32:47,170 --> 00:32:50,710 Here's the notion of an allosteric activator. 448 00:32:50,710 --> 00:32:55,850 Here's the enzyme, and here's the enzyme with its substrate. 449 00:32:55,850 --> 00:32:58,620 And here's its allosteric site. 450 00:32:58,620 --> 00:33:03,600 And it can't work until an allosteric activator, which is 451 00:33:03,600 --> 00:33:04,620 not the substrate-- 452 00:33:04,620 --> 00:33:06,230 it's a different molecule-- 453 00:33:06,230 --> 00:33:10,080 binds to the allosteric site and then makes the active site 454 00:33:10,080 --> 00:33:13,270 the correct shape to fit the substrate so that 455 00:33:13,270 --> 00:33:14,720 the enzyme can work. 456 00:33:14,720 --> 00:33:19,170 And you can get a cycle here again, so that you get 457 00:33:19,170 --> 00:33:22,260 catalysis, and the whole thing can take place again. 458 00:33:27,200 --> 00:33:30,120 I want to show you, to give you a sense of the kind of 459 00:33:30,120 --> 00:33:33,390 complexity of what this all looks like, a particular 460 00:33:33,390 --> 00:33:35,870 example of an enzyme reaction. 461 00:33:35,870 --> 00:33:38,930 And I'll show you an animation that goes with this, to give 462 00:33:38,930 --> 00:33:42,040 you a sense of how these things work. 463 00:33:42,040 --> 00:33:43,850 The enzyme I'm going to focus on is called 464 00:33:43,850 --> 00:33:45,980 dihydrofolate reductase. 465 00:33:45,980 --> 00:33:47,380 That's an essential enzyme. 466 00:33:47,380 --> 00:33:51,530 It's required for nucleotide synthesis, DNA modification. 467 00:33:51,530 --> 00:33:55,100 And the reason you take folate, or folic acid, is to 468 00:33:55,100 --> 00:33:57,500 allow dihydrofolate to actually work -- 469 00:33:57,500 --> 00:34:00,570 dihydrofolate reductase to work. 470 00:34:00,570 --> 00:34:02,850 The substrate is dihydrofolate. 471 00:34:02,850 --> 00:34:04,560 It's a complicated molecule. 472 00:34:04,560 --> 00:34:07,490 But I've circled the important part. 473 00:34:07,490 --> 00:34:10,770 You can see there's a double bond here which is going to be 474 00:34:10,770 --> 00:34:13,560 reduced when the enzyme acts. 475 00:34:13,560 --> 00:34:17,060 And here is the reduced form or tetrahydrofolate of 476 00:34:17,060 --> 00:34:18,540 dihydrofolate reductase. 477 00:34:18,540 --> 00:34:19,880 You don't need to take notes on this. 478 00:34:19,880 --> 00:34:23,570 Just look and listen. 479 00:34:23,570 --> 00:34:25,690 Here is a structure of the protein. 480 00:34:25,690 --> 00:34:28,989 You can see the alpha helices in brown and the beta sheets 481 00:34:28,989 --> 00:34:30,760 in blue and this kind of unstructured 482 00:34:30,760 --> 00:34:33,280 loopy stuff in between. 483 00:34:33,280 --> 00:34:38,129 And here is the substrate dihydrofolate binding to its 484 00:34:38,129 --> 00:34:39,570 active site. 485 00:34:39,570 --> 00:34:43,739 Dihydrofolate reductase requires a coenzyme, something 486 00:34:43,739 --> 00:34:47,719 called NADPH, which is a very important coenzyme. 487 00:34:47,719 --> 00:34:51,420 It's also part of the energy production cycle. 488 00:34:51,420 --> 00:34:54,739 And dihydrofolate reductase is not only essential for life 489 00:34:54,739 --> 00:34:58,040 but it's a target of the anticancer drug methotrexate 490 00:34:58,040 --> 00:35:00,205 and of trimethoprim, which is an antibiotic. 491 00:35:04,140 --> 00:35:07,150 This is an animation which will show you how 492 00:35:07,150 --> 00:35:11,380 dihydrofolate binds to dihydrofolate reductase, how 493 00:35:11,380 --> 00:35:16,840 NADPH comes in, and how NADPH donates the hydrogens that 494 00:35:16,840 --> 00:35:19,750 will allow dihydrofolate to be reduced. 495 00:35:19,750 --> 00:35:22,890 So let me start the animation, and I'll point things out as 496 00:35:22,890 --> 00:35:25,090 you're watching it. 497 00:35:25,090 --> 00:35:26,830 And you'll see it's quick. 498 00:35:26,830 --> 00:35:30,750 Here is the coenzyme coming in. 499 00:35:30,750 --> 00:35:36,540 And here is the substrate dihydrofolate. 500 00:35:36,540 --> 00:35:40,230 And if you look at it, you'll see that the coenzyme is near 501 00:35:40,230 --> 00:35:42,130 the active site. 502 00:35:42,130 --> 00:35:46,690 And as it binds first, donates its hydrogens to 503 00:35:46,690 --> 00:35:52,070 dihydrofolate, which then becomes tetrahydrofolate, is 504 00:35:52,070 --> 00:35:54,010 released from the enzyme. 505 00:35:54,010 --> 00:35:55,860 There are a number of things you can see here. 506 00:35:55,860 --> 00:35:57,730 You can see the enzyme cycle. 507 00:35:57,730 --> 00:36:00,610 You can see this goes over and over again. 508 00:36:00,610 --> 00:36:03,050 You can see that the enzyme, the protein 509 00:36:03,050 --> 00:36:04,570 structure, is changing. 510 00:36:04,570 --> 00:36:08,400 It's moving as the coenzyme is binding, as the 511 00:36:08,400 --> 00:36:10,250 substrate is binding. 512 00:36:10,250 --> 00:36:13,000 You can see that there's a chemical reaction going on 513 00:36:13,000 --> 00:36:18,270 here as the NADPH is giving its hydrogens to this 514 00:36:18,270 --> 00:36:19,760 dihydrofolate. 515 00:36:19,760 --> 00:36:23,240 And you can get a sense of the kind of 516 00:36:23,240 --> 00:36:25,440 animation that is enzymes. 517 00:36:25,440 --> 00:36:26,830 This is an animation. 518 00:36:26,830 --> 00:36:29,580 No one's actually seen an enzyme work like this because 519 00:36:29,580 --> 00:36:32,460 it's impossible to take real movies like this. 520 00:36:32,460 --> 00:36:36,190 But based on the structure of the enzyme and the binding of 521 00:36:36,190 --> 00:36:39,910 NADPH and the substrate to the enzyme, these authors have 522 00:36:39,910 --> 00:36:43,480 reconstructed this really beautiful movie which gives 523 00:36:43,480 --> 00:36:46,560 you a sense how enzymes work in action. 524 00:36:46,560 --> 00:36:46,950 Okay. 525 00:36:46,950 --> 00:36:48,410 I'll post this on your website. 526 00:36:48,410 --> 00:36:49,660 And you can watch it. 527 00:36:53,450 --> 00:37:00,210 The last two things I want to tell you are that, firstly, 528 00:37:00,210 --> 00:37:03,520 enzymes don't work as one-off deals. 529 00:37:03,520 --> 00:37:06,410 They work as part of a production line. 530 00:37:06,410 --> 00:37:09,430 And the production line is called a pathway. 531 00:37:09,430 --> 00:37:12,070 And like any good production line, as I've mentioned 532 00:37:12,070 --> 00:37:15,360 already, there are checks and balances to make sure that the 533 00:37:15,360 --> 00:37:19,190 production line is working at optimal speed and making what 534 00:37:19,190 --> 00:37:21,530 it needs to make. 535 00:37:21,530 --> 00:37:27,756 So we can talk about pathways and feedback. 536 00:37:32,220 --> 00:37:35,000 And let's draw a simple pathway on the board to give 537 00:37:35,000 --> 00:37:36,960 you a sense of what I mean. 538 00:37:36,960 --> 00:37:41,030 Let's start off with a substrate that's converted 539 00:37:41,030 --> 00:37:47,390 through the action of enzyme one to product one. 540 00:37:47,390 --> 00:37:51,670 And then there is also a competing pathway where this-- 541 00:37:51,670 --> 00:37:54,290 Actually, lets make it product one. 542 00:37:54,290 --> 00:37:56,885 Or we can call it substrate two. 543 00:37:56,885 --> 00:38:01,080 But let's call it product one, and then through the action of 544 00:38:01,080 --> 00:38:05,230 enzyme two, to product one. 545 00:38:05,230 --> 00:38:08,890 And here's a competing pathway where the substrate, through 546 00:38:08,890 --> 00:38:13,560 the action of enzyme three makes product three, and then 547 00:38:13,560 --> 00:38:18,340 through enzyme four action, makes product four. 548 00:38:18,340 --> 00:38:19,410 Okay. 549 00:38:19,410 --> 00:38:20,400 This is a pathway. 550 00:38:20,400 --> 00:38:22,660 It's a bifurcating pathway. 551 00:38:22,660 --> 00:38:29,430 It may be that's if you've got this branch, the E3-E4 branch 552 00:38:29,430 --> 00:38:33,020 of the pathway active, you actually want to shut off 553 00:38:33,020 --> 00:38:35,560 production of the other pathway. 554 00:38:35,560 --> 00:38:39,880 And it may be that if you get product four made, you 555 00:38:39,880 --> 00:38:44,950 actually want to shut off production of product two. 556 00:38:47,680 --> 00:38:52,820 In that case, you could draw a line like this-- you could 557 00:38:52,820 --> 00:38:56,440 make it up, whatever you like. 558 00:38:56,440 --> 00:38:59,110 But for the example I'm giving you, I'm telling you that when 559 00:38:59,110 --> 00:39:02,910 you've got lots of product four, it's going to shut off 560 00:39:02,910 --> 00:39:05,370 the other branch of the pathway. 561 00:39:05,370 --> 00:39:09,000 And this nomenclature is as follows. 562 00:39:09,000 --> 00:39:10,955 An arrow means activate. 563 00:39:13,780 --> 00:39:17,840 And what's called a T-bar means inhibit. 564 00:39:17,840 --> 00:39:21,570 And these are very standard nomenclatures in biology that 565 00:39:21,570 --> 00:39:23,270 you should know. 566 00:39:23,270 --> 00:39:26,820 So this T-bar here is inhibit. 567 00:39:26,820 --> 00:39:29,730 It's also called negative feedback. 568 00:39:36,270 --> 00:39:40,000 At the same time, you might get positive feedback. 569 00:39:40,000 --> 00:39:46,580 It may be that if you have some of product three, you 570 00:39:46,580 --> 00:39:49,570 actually want more of product one. 571 00:39:49,570 --> 00:39:54,390 And in that case, product three might activate enzyme 572 00:39:54,390 --> 00:39:57,180 one so that you actually activate the other branch. 573 00:39:57,180 --> 00:39:58,790 This is a complicated pathway. 574 00:39:58,790 --> 00:40:01,510 There's a lot of competition going on here. 575 00:40:01,510 --> 00:40:08,420 But in that case, that activation would be positive. 576 00:40:08,420 --> 00:40:13,300 And so for this example, my star 577 00:40:13,300 --> 00:40:14,635 would be positive feedback. 578 00:40:20,370 --> 00:40:25,470 And my T-bar, which I'll make a pound sign, would be a 579 00:40:25,470 --> 00:40:26,720 negative feedback. 580 00:40:29,910 --> 00:40:32,610 This is a really pivotal concept in biology. 581 00:40:32,610 --> 00:40:35,570 It's not just true of enzyme pathways, it's true of 582 00:40:35,570 --> 00:40:37,790 multiple chemical reactions. 583 00:40:37,790 --> 00:40:39,650 And you really need to understand 584 00:40:39,650 --> 00:40:41,790 this aspect of biology. 585 00:40:41,790 --> 00:40:47,000 The last thing that I want to tell you has to do, very 586 00:40:47,000 --> 00:40:52,300 briefly, with where the energy comes from that cells use for 587 00:40:52,300 --> 00:40:54,500 chemical reactions. 588 00:40:54,500 --> 00:40:57,300 And what I'm going to tell you very briefly, in about two 589 00:40:57,300 --> 00:41:02,020 seconds, is that in the cell, there are very controlled 590 00:41:02,020 --> 00:41:06,570 amounts of energy that are contained in a nucleotide 591 00:41:06,570 --> 00:41:09,880 called ATP. 592 00:41:09,880 --> 00:41:15,350 ATP is a nucleotide triphosphate. 593 00:41:15,350 --> 00:41:18,030 We talked about nucleotides before. 594 00:41:18,030 --> 00:41:23,440 The triphosphate is very important here. 595 00:41:23,440 --> 00:41:30,110 And this nucleotide triphosphate is kind of like 596 00:41:30,110 --> 00:41:33,600 the dollars and cents of energy currency in the cell. 597 00:41:33,600 --> 00:41:36,760 If a chemical reaction needs energy, the cell 598 00:41:36,760 --> 00:41:40,390 uses ATP to get it. 599 00:41:40,390 --> 00:41:50,890 ATP is hydrolyzed to give rise to ADP, adenosine diphosphate, 600 00:41:50,890 --> 00:41:57,060 and PPI, inorganic phosphate, plus an increment of energy. 601 00:41:57,060 --> 00:42:00,090 This is an exergonic reaction. 602 00:42:00,090 --> 00:42:12,340 This energy is then used for chemical reactions, to build 603 00:42:12,340 --> 00:42:17,600 or to break down various molecules. 604 00:42:17,600 --> 00:42:20,210 For this reaction, delta G is negative. 605 00:42:23,570 --> 00:42:25,425 That is why there's energy released. 606 00:42:28,830 --> 00:42:32,860 And this energy is used for two types of reactions-- 607 00:42:32,860 --> 00:42:42,600 those that are catabolic, that break down molecules, and 608 00:42:42,600 --> 00:42:52,320 those that are anabolic, which build up molecules. 609 00:42:52,320 --> 00:42:55,340 We're not going to talk about generation of ATP. 610 00:42:55,340 --> 00:42:56,640 That is a separate topic. 611 00:42:56,640 --> 00:42:59,640 And those of you who are go on to do biochemistry will talk 612 00:42:59,640 --> 00:43:01,620 about it in great detail. 613 00:43:01,620 --> 00:43:06,530 But I do have some slides on here that I will refer to. 614 00:43:06,530 --> 00:43:06,635 Here is -- 615 00:43:06,635 --> 00:43:08,820 This is the last thing I'll show you. 616 00:43:08,820 --> 00:43:10,140 Please wait for it. 617 00:43:10,140 --> 00:43:12,800 Here is adenosine triphosphate. 618 00:43:12,800 --> 00:43:15,350 Here is the high-energy bond that is 619 00:43:15,350 --> 00:43:17,470 broken to release energy. 620 00:43:17,470 --> 00:43:18,720 And we'll stop there.