1 00:00:00,000 --> 00:00:03,000 Today we're going to start get into at least the nitty-gritty stuff of 2 00:00:03,000 --> 00:00:07,000 the course. I think a point I want to, just to give you a very broad 3 00:00:07,000 --> 00:00:10,000 perspective apart from why biology is interesting, 4 00:00:10,000 --> 00:00:14,000 I want to talk about just very briefly how we study biology. 5 00:00:14,000 --> 00:00:17,000 I sort of talked about it the other day by sort of the levels at which 6 00:00:17,000 --> 00:00:21,000 we could do it, from the biosphere all the way down 7 00:00:21,000 --> 00:00:24,000 to the molecular level. But there is another way of looking 8 00:00:24,000 --> 00:00:28,000 at it. And I just want to remind you of what I said the other day. 9 00:00:28,000 --> 00:00:32,000 Biology is an experimental science 10 00:00:32,000 --> 00:00:38,000 What we know or think we know at the 11 00:00:38,000 --> 00:00:42,000 moment is because of people having made observations, 12 00:00:42,000 --> 00:00:45,000 designed hypotheses, tested them and so on. 13 00:00:45,000 --> 00:00:49,000 And what you're seeing is sort of the sum of the current state of 14 00:00:49,000 --> 00:00:52,000 human knowledge when I'm talking to you right now. 15 00:00:52,000 --> 00:00:56,000 There are various, two sort of major disciplines that 16 00:00:56,000 --> 00:01:00,000 have been used to get at how biological function works. 17 00:01:00,000 --> 00:01:04,000 As you'll see, the main actor for many of the 18 00:01:04,000 --> 00:01:08,000 things that happened inside of cells and in living organisms are proteins. 19 00:01:08,000 --> 00:01:12,000 And we'll be talking about what those are and their structures in 20 00:01:12,000 --> 00:01:16,000 some detail at the next thing. But the information is not coded in 21 00:01:16,000 --> 00:01:20,000 the proteins. The information for coding everything that's in a cell 22 00:01:20,000 --> 00:01:24,000 is in units called genes which are made of, as you probably 23 00:01:24,000 --> 00:01:27,000 all know, DNA. So there have been, 24 00:01:27,000 --> 00:01:31,000 classically there were two approaches towards studying biology 25 00:01:31,000 --> 00:01:34,000 in detailed ways. One was the approach of the 26 00:01:34,000 --> 00:01:38,000 biochemist who basically took whatever it was, 27 00:01:38,000 --> 00:01:42,000 put it in a whirling blender or something, and ripped everything 28 00:01:42,000 --> 00:01:45,000 into little pieces. Sort of like taking the alarm clock 29 00:01:45,000 --> 00:01:49,000 and shaking it so hard all you've got is all the little bits. 30 00:01:49,000 --> 00:01:52,000 And once you got it into all little bits then you can purify a little 31 00:01:52,000 --> 00:01:56,000 thing like a spring or a little wheel or something and try then to 32 00:01:56,000 --> 00:02:00,000 figure out what that does in the context of the cell. 33 00:02:00,000 --> 00:02:05,000 You can get very detailed information. And this is in a sort 34 00:02:05,000 --> 00:02:11,000 of trivial way the science of, discipline of biochemistry. 35 00:02:11,000 --> 00:02:17,000 Geneticists take a different sort of approach. And what they do is they 36 00:02:17,000 --> 00:02:23,000 take the living organism and look for a variant where there has just 37 00:02:23,000 --> 00:02:29,000 been one single change in that whole organism and they study 38 00:02:29,000 --> 00:02:33,000 its properties. And what you learn from that is 39 00:02:33,000 --> 00:02:37,000 physiologically relevant information. And if you broke up a car and 40 00:02:37,000 --> 00:02:41,000 purified the ashtray you could postulate that that was really 41 00:02:41,000 --> 00:02:45,000 important for the car. But if you made a mutant that was 42 00:02:45,000 --> 00:02:48,000 missing the ashtray and it still ran, you know, you'd learn that that 43 00:02:48,000 --> 00:02:52,000 wasn't what was correct. And one of the really powerful 44 00:02:52,000 --> 00:02:56,000 things that people could only do in very rare instances for a long time 45 00:02:56,000 --> 00:03:00,000 was to unite the kinds of observations that biochemists made 46 00:03:00,000 --> 00:03:04,000 with the kinds of observations geneticists made. 47 00:03:04,000 --> 00:03:08,000 And the explosion in knowledge that's happened over the last couple 48 00:03:08,000 --> 00:03:12,000 of decades, probably, well, since probably 1975 when 49 00:03:12,000 --> 00:03:16,000 recombinant DNA came in, was a whole new realm of sort of a 50 00:03:16,000 --> 00:03:20,000 general discipline we call molecular biology that allowed us to clone 51 00:03:20,000 --> 00:03:24,000 genes, to sequence them, to many of the things we'll be 52 00:03:24,000 --> 00:03:27,000 talking about. But one of the real powers in 53 00:03:27,000 --> 00:03:31,000 looking at this sort of way of thinking about how we study biology 54 00:03:31,000 --> 00:03:34,000 is that it suddenly enabled one to put these two sorts of things 55 00:03:34,000 --> 00:03:38,000 together. If you were a biochemist and you purified a protein and you 56 00:03:38,000 --> 00:03:41,000 found out a chemical property that it had and you wondered what it did 57 00:03:41,000 --> 00:03:45,000 in the cell, you could sequence the protein and deduce what some of the 58 00:03:45,000 --> 00:03:49,000 DNA sequence was, find the gene, disable the gene in 59 00:03:49,000 --> 00:03:52,000 the organism, look and see if your idea was right. 60 00:03:52,000 --> 00:03:56,000 Or vice versa, if you were a geneticist and you found a mutant 61 00:03:56,000 --> 00:03:59,000 that had an interesting property and you wondered how it was working then 62 00:03:59,000 --> 00:04:03,000 you could clone the gene, look at the protein and try and 63 00:04:03,000 --> 00:04:07,000 figure it out. And that's partly way since about 64 00:04:07,000 --> 00:04:13,000 1975 there has just been this absolute upheaval in our knowledge 65 00:04:13,000 --> 00:04:18,000 of biology. And we'll be talking about all of these disciplines here 66 00:04:18,000 --> 00:04:24,000 as we go through the course. Three or four of you were honest 67 00:04:24,000 --> 00:04:30,000 enough to say I'd rather be anywhere on earth but in this class. 68 00:04:30,000 --> 00:04:33,000 I'm a senior. I really didn't want to be here. And I said to you the 69 00:04:33,000 --> 00:04:37,000 other day if you'll come I'll give you the best I have to try and show 70 00:04:37,000 --> 00:04:40,000 you why I think it's exciting and why it's so relevant to you and your 71 00:04:40,000 --> 00:04:44,000 life as you go looking forward to moving on with your careers and your 72 00:04:44,000 --> 00:04:47,000 family and everything else. However, even if you're not 73 00:04:47,000 --> 00:04:51,000 interested in this course, don't get caught in the trap because 74 00:04:51,000 --> 00:04:54,000 we're not going to be doing differential equations that it's 75 00:04:54,000 --> 00:04:58,000 easy. Part of the reason biology is hard is each one of these 76 00:04:58,000 --> 00:05:02,000 disciplines has a different kind of thinking. 77 00:05:02,000 --> 00:05:05,000 And to be very effective in biology right now you have to be able to 78 00:05:05,000 --> 00:05:08,000 think like a chemist, how bonds are formed and broken and 79 00:05:08,000 --> 00:05:11,000 what's reasonable. You need to be able to think in 80 00:05:11,000 --> 00:05:15,000 3-dimensional structures because everything happens in 3-D and 81 00:05:15,000 --> 00:05:18,000 biology is very much about fitting shapes together. 82 00:05:18,000 --> 00:05:21,000 Genetics is more like probability and statistics. 83 00:05:21,000 --> 00:05:25,000 Some of those logic games that you sort of used to try and do. 84 00:05:25,000 --> 00:05:28,000 It's more like that. PCR is, I don't know, recombinant DNA, all 85 00:05:28,000 --> 00:05:32,000 this sort of stuff is sort of a strategy kind of game. 86 00:05:32,000 --> 00:05:35,000 So you'll find, as you go through this course, 87 00:05:35,000 --> 00:05:38,000 that there maybe some things that are easy and some that are difficult. 88 00:05:38,000 --> 00:05:41,000 But for you, easier or difficult, you'll need to do a lot of different 89 00:05:41,000 --> 00:05:45,000 thinking. And then, at the moment, you cannot do biology 90 00:05:45,000 --> 00:05:48,000 anymore by just being a biochemist or just being a geneticist. 91 00:05:48,000 --> 00:05:51,000 You could in the old days, but now you've got to do it all. 92 00:05:51,000 --> 00:05:54,000 So where we're going to start right now will be with biochemistry. 93 00:05:54,000 --> 00:05:58,000 And just before I do that I just want to show you -- 94 00:05:58,000 --> 00:06:01,000 Let's see. I wonder if we're going to be able to see these slides with 95 00:06:01,000 --> 00:06:04,000 that light on. I think we'll see if we can do this. 96 00:06:04,000 --> 00:06:07,000 So the green fluorescent protein, thanks, that's great. The green 97 00:06:07,000 --> 00:06:10,000 fluorescent protein, which we showed you the other day, 98 00:06:10,000 --> 00:06:13,000 is a protein. And we're going to be talking about that. 99 00:06:13,000 --> 00:06:16,000 And you'll see it's got structures. You've got these sorts of sheets 100 00:06:16,000 --> 00:06:19,000 and you'll see little helices. And in a couple of days you'll know 101 00:06:19,000 --> 00:06:22,000 what this is all about. But I wanted to tell you a couple 102 00:06:22,000 --> 00:06:26,000 of things just before I get into this. 103 00:06:26,000 --> 00:06:30,000 This actually was, I showed you that little Barney 104 00:06:30,000 --> 00:06:34,000 thing to try to emphasize that if you looked at evolution that way, 105 00:06:34,000 --> 00:06:38,000 you can see most of it was at the level of single cells, 106 00:06:38,000 --> 00:06:42,000 and that's why things are so common when you get down to the cellular 107 00:06:42,000 --> 00:06:46,000 and molecular level. I've actually done that demo one 108 00:06:46,000 --> 00:06:50,000 other place, and that was after, I'm an American Cancer Society 109 00:06:50,000 --> 00:06:54,000 research professor, and they asked me to give a talk for 110 00:06:54,000 --> 00:06:58,000 the 50th anniversary of the Illinois Division of the American Cancer 111 00:06:58,000 --> 00:07:03,000 Society of the importance of basic research. 112 00:07:03,000 --> 00:07:06,000 And it was after dinner, 500 people in tuxedos and evening 113 00:07:06,000 --> 00:07:09,000 gowns and bottles of wine, and they kept shortening my time. 114 00:07:09,000 --> 00:07:12,000 And finally I had ten minutes to get up there in my tux and tell them 115 00:07:12,000 --> 00:07:16,000 about the importance of research, basic research. And I finally 116 00:07:16,000 --> 00:07:19,000 decided maybe what I could do is help them understand why when they 117 00:07:19,000 --> 00:07:22,000 gave money to cure cancer biologists went, ah, signed this one off, 118 00:07:22,000 --> 00:07:25,000 and studied all these other organisms, fruit flies and 119 00:07:25,000 --> 00:07:29,000 everything. So I did this little demo. So I was up on the stage at 120 00:07:29,000 --> 00:07:32,000 the Sheraton holding the Barney and the dinosaur doing what 121 00:07:32,000 --> 00:07:35,000 you saw me do here. And I thought of briefly about 122 00:07:35,000 --> 00:07:38,000 putting my tux on just to kind of, you know, give a little zip to the 123 00:07:38,000 --> 00:07:41,000 extra lecture, but decided not to because I'd get 124 00:07:41,000 --> 00:07:45,000 chalk all over it or something. So if you think I look stupid doing 125 00:07:45,000 --> 00:07:48,000 this, you know, my cats thought I was absolutely an 126 00:07:48,000 --> 00:07:51,000 idiot afterwards. They looked very, 127 00:07:51,000 --> 00:07:54,000 very puzzled as to what was going on. OK. So I'm going to start talking 128 00:07:54,000 --> 00:07:57,000 in a couple of minutes about covalent bonds, 129 00:07:57,000 --> 00:08:00,000 and you're going to roll your eyes upwards and think I've heard about 130 00:08:00,000 --> 00:08:04,000 that since I was a baby, or some of you will think that. 131 00:08:04,000 --> 00:08:07,000 But I just want to keep, you've got to understand something 132 00:08:07,000 --> 00:08:10,000 about how the parts that are used in biology are built or it won't make 133 00:08:10,000 --> 00:08:13,000 sense. And so just to sort of give you something to sort of keep you 134 00:08:13,000 --> 00:08:17,000 going here, I want to sort of foreshadow a couple of things that 135 00:08:17,000 --> 00:08:20,000 are coming. Here's an example of what happens with genetics. 136 00:08:20,000 --> 00:08:23,000 This is a single mutation in one gene of an individual. 137 00:08:23,000 --> 00:08:26,000 This woman has what's known as Werner syndrome. 138 00:08:26,000 --> 00:08:30,000 That's what she looked like as a teenager. 139 00:08:30,000 --> 00:08:33,000 That's what she looked like at age 48. That's one of these mutations 140 00:08:33,000 --> 00:08:37,000 that causes advanced aging. And people are working very hard on 141 00:08:37,000 --> 00:08:40,000 what that, you know, trying to understand aging. 142 00:08:40,000 --> 00:08:44,000 During your time at MIT, there are going to be some, 143 00:08:44,000 --> 00:08:47,000 there already have been some amazing discoveries in the last five years, 144 00:08:47,000 --> 00:08:51,000 and it's going to be a time of explosive growth. 145 00:08:51,000 --> 00:08:55,000 But that's just one change. And it offers a huge clue as to why 146 00:08:55,000 --> 00:08:58,000 we age. Here's another example. These are people who have a human 147 00:08:58,000 --> 00:09:02,000 condition called Xeroderma Pigmentosum. And this was the way 148 00:09:02,000 --> 00:09:06,000 they used to look before we understood it. 149 00:09:06,000 --> 00:09:10,000 They have a deficiency in handling damage to their DNA that's caused by 150 00:09:10,000 --> 00:09:13,000 sunlight. So if they went out in the sunlight once they'd get skin 151 00:09:13,000 --> 00:09:17,000 cancer. You can see they get skin lesions and everything else. 152 00:09:17,000 --> 00:09:21,000 It was due to a defect in just one gene. And it took out an important 153 00:09:21,000 --> 00:09:25,000 kind of DNA repair. Now they know how it works. 154 00:09:25,000 --> 00:09:29,000 The kids who do this only go out at night. 155 00:09:29,000 --> 00:09:32,000 They go to summer camp at night. They call them ìChildren of the 156 00:09:32,000 --> 00:09:35,000 Moonî. They look normal and they don't get skin cancer, 157 00:09:35,000 --> 00:09:38,000 but they have to live a kind of special life because of this problem. 158 00:09:38,000 --> 00:09:41,000 And people are working on fixing that. That's the sort of thing that 159 00:09:41,000 --> 00:09:44,000 can come out genetics. Single change, absolutely dramatic 160 00:09:44,000 --> 00:09:47,000 affect. You can sort of make inferences that something important 161 00:09:47,000 --> 00:09:50,000 is broken in that individual because the rest of us don't have this 162 00:09:50,000 --> 00:09:53,000 problem. The biochemists, you know Watson and Crick, and we'll 163 00:09:53,000 --> 00:09:56,000 talk more about their structure of DNA. But DNA has to 164 00:09:56,000 --> 00:10:00,000 get replicated. In fact, just in the last couple 165 00:10:00,000 --> 00:10:04,000 years we now know that's what's wrong with this person is that 166 00:10:04,000 --> 00:10:09,000 they're lacking a special DNA copying machine that is able to copy 167 00:10:09,000 --> 00:10:13,000 over strands of DNA that have damage in them that's caused by sunlight. 168 00:10:13,000 --> 00:10:17,000 It's got a very sort of flexible active site. It can accommodate the 169 00:10:17,000 --> 00:10:22,000 bulkiness of this UV induced lesion. And so here's a case where we've 170 00:10:22,000 --> 00:10:26,000 now united our understanding of that disease at the ultimate biochemical 171 00:10:26,000 --> 00:10:31,000 molecular level and the high level human syndrome. 172 00:10:31,000 --> 00:10:35,000 So that's kind of one thing to sort of keep you going. 173 00:10:35,000 --> 00:10:39,000 OK. So here's a cell. That's the fundamental unit of life. 174 00:10:39,000 --> 00:10:43,000 I said the other day member cells carry out metabolism. 175 00:10:43,000 --> 00:10:48,000 They do regulated growth. They do reproduction. That's what 176 00:10:48,000 --> 00:10:52,000 makes them different from just a bag of proteins and nucleic acids and 177 00:10:52,000 --> 00:10:56,000 things. And we could think about cells at a couple of 178 00:10:56,000 --> 00:11:01,000 different levels. We could think about them in terms 179 00:11:01,000 --> 00:11:06,000 of their atomic composition. I guess we can. Let's see. And if 180 00:11:06,000 --> 00:11:12,000 we think about it that way it's not particularly exciting. 181 00:11:12,000 --> 00:11:17,000 Hydrogen is about 60%, oxygen is about 20%, carbon is about 182 00:11:17,000 --> 00:11:22,000 12%, nitrogen is about 5%, and then there's a whole lot of 183 00:11:22,000 --> 00:11:28,000 other stuff present at lower levels, phosphorus, sulfate, magnesium, 184 00:11:28,000 --> 00:11:34,000 manganese, selenium, etc. This isn't a particularly helpful 185 00:11:34,000 --> 00:11:41,000 way to think about cells. This is perhaps a more useful way, 186 00:11:41,000 --> 00:11:49,000 and that's to think about it in terms of molecular composition. 187 00:11:49,000 --> 00:11:56,000 And we're about 80% water. 188 00:11:56,000 --> 00:12:00,000 Virtually all living organisms, more or less the same, 80% water is 189 00:12:00,000 --> 00:12:05,000 what our cells are made up of. And of the rest of them, 190 00:12:05,000 --> 00:12:09,000 there are four major classes of macromolecule, 191 00:12:09,000 --> 00:12:13,000 large biological molecules that make up the rest of cells. 192 00:12:13,000 --> 00:12:17,000 And that's what we're going to be focusing on in a little bit. 193 00:12:17,000 --> 00:12:22,000 There are proteins, which I've already mentioned today, 194 00:12:22,000 --> 00:12:26,000 and that's about 50% of it. Nucleic acids, that's DNA and RNA, 195 00:12:26,000 --> 00:12:30,000 we'll say that's about 15%. Carbohydrates, 196 00:12:30,000 --> 00:12:35,000 which we'll be talking about today. Lipids about 10%. 197 00:12:35,000 --> 00:12:39,000 And there is a bunch of little stuff that is important but makes up 198 00:12:39,000 --> 00:12:43,000 the remaining amount. But to understand biology we're 199 00:12:43,000 --> 00:12:48,000 really going to have to try and figure out how cells work. 200 00:12:48,000 --> 00:12:52,000 We're going to need to talk about the properties of those molecules. 201 00:12:52,000 --> 00:12:56,000 And just so you'll know, this picture is actually, 202 00:12:56,000 --> 00:13:01,000 this was made by somebody at Lawrence Berkeley National Labs. 203 00:13:01,000 --> 00:13:04,000 As far as I know she still hasn't published it. This is an image of 204 00:13:04,000 --> 00:13:08,000 an actual cell. It's made by a very fancy technique 205 00:13:08,000 --> 00:13:12,000 called x-ray tomography where she sort of takes a zillion little sort 206 00:13:12,000 --> 00:13:15,000 of slices and then assembles the whole thing. This is a yeast cell. 207 00:13:15,000 --> 00:13:19,000 That purple thing, artificially colored, is the nucleus. 208 00:13:19,000 --> 00:13:23,000 This thing in the middle is a big storage thing called a vacuole in 209 00:13:23,000 --> 00:13:27,000 the cell. We cannot see the other cellular components right now, 210 00:13:27,000 --> 00:13:31,000 but that is a real cell. It looks like a textbook, 211 00:13:31,000 --> 00:13:35,000 but it's actually a yeast cell that got its picture taken by this very 212 00:13:35,000 --> 00:13:39,000 fancy thing. So, as I say, we're going to charge 213 00:13:39,000 --> 00:13:43,000 right now into starting to think about these various molecular forces 214 00:13:43,000 --> 00:13:47,000 that make possible, that give these various biomolecules 215 00:13:47,000 --> 00:13:51,000 or biomacromolecules their properties. And I just want to give 216 00:13:51,000 --> 00:13:55,000 you sort of a game plan for how we're going to do this over the next 217 00:13:55,000 --> 00:13:59,000 couple of lessons, couple of classes. 218 00:13:59,000 --> 00:14:08,000 They're sort of classes of chemical forces. And today we'll be talking 219 00:14:08,000 --> 00:14:17,000 about covalent bonds and hydrogen bonds. And we'll go onto to talk 220 00:14:17,000 --> 00:14:26,000 about other ones in the next class or two. And then we're going to 221 00:14:26,000 --> 00:14:35,000 talk about these biological macromolecules that I just listed. 222 00:14:35,000 --> 00:14:40,000 Proteins. Actually, the order we'll be talking about 223 00:14:40,000 --> 00:14:45,000 them, carbohydrates, nucleic acids, proteins and lipids. 224 00:14:45,000 --> 00:14:50,000 So the way I'm going to do this is I can tell you about the properties 225 00:14:50,000 --> 00:14:56,000 of carbohydrates by just talking about covalent bonds and hydrogen 226 00:14:56,000 --> 00:15:01,000 bonds. And once we've discussed those we'll go on here and I'll give 227 00:15:01,000 --> 00:15:05,000 you a couple of examples. And once we've learned some more 228 00:15:05,000 --> 00:15:08,000 we'll go on and I'll give you some other examples. 229 00:15:08,000 --> 00:15:11,000 And, as I said, in a second I'm going to say 230 00:15:11,000 --> 00:15:14,000 covalent bonds. It's going to seem boring. 231 00:15:14,000 --> 00:15:17,000 Here's just something to sort of keep in, we'll get another one in a 232 00:15:17,000 --> 00:15:21,000 minute, to look ahead, why do we want to do this sort of 233 00:15:21,000 --> 00:15:24,000 stuff? I showed you this picture the other day. 234 00:15:24,000 --> 00:15:27,000 These are E. coli swimming along. Those things I told you are those 235 00:15:27,000 --> 00:15:30,000 sort of long spiral things are bundles of protein filaments 236 00:15:30,000 --> 00:15:33,000 called flagella. They're being rotated by a motor at 237 00:15:33,000 --> 00:15:37,000 the end of the bacterium that's rotating ten to a hundred thousand 238 00:15:37,000 --> 00:15:41,000 RPM. And that thing is moving at such a rate, so many body lengths a 239 00:15:41,000 --> 00:15:45,000 second that if it was me moving at that speed I'd be going 300 miles 240 00:15:45,000 --> 00:15:48,000 per hour that many body lengths. So these are bacteria swimming 241 00:15:48,000 --> 00:15:52,000 around. The motor that drives them is made of proteins. 242 00:15:52,000 --> 00:15:56,000 And this is a textbook representation of that motor. 243 00:15:56,000 --> 00:16:00,000 It has familiar parts to some of you. 244 00:16:00,000 --> 00:16:03,000 Here's a rotator. There's a bushing. 245 00:16:03,000 --> 00:16:06,000 There's a drive shaft and so on. It's got parts that you would 246 00:16:06,000 --> 00:16:09,000 recognize as an engineer, but it's all made out of proteins. 247 00:16:09,000 --> 00:16:13,000 And that's a textbook diagram. What I want to show you in the next 248 00:16:13,000 --> 00:16:16,000 slide is they've taken a whole lot of electron micrographic images of 249 00:16:16,000 --> 00:16:19,000 those things, and the resolution isn't so good, 250 00:16:19,000 --> 00:16:23,000 but they averaged a whole bunch of them. And this is what it looks 251 00:16:23,000 --> 00:16:26,000 like. So you can sort of see this really is a machine. It's 252 00:16:26,000 --> 00:16:30,000 built of proteins. And to understand how these machines 253 00:16:30,000 --> 00:16:34,000 work you have to understand some of these forces. So that's why I'm 254 00:16:34,000 --> 00:16:39,000 going to start in and we're going to begin with covalent bonds so that 255 00:16:39,000 --> 00:16:43,000 we're all on the same page right from the beginning. 256 00:16:43,000 --> 00:16:48,000 And another aspect, as you'll see, even though you may 257 00:16:48,000 --> 00:16:52,000 have heard about some of these bonds before, there's a new issue that's 258 00:16:52,000 --> 00:16:57,000 going to need to occupy your attention. And that is, 259 00:16:57,000 --> 00:17:01,000 what's the strength of the bond in the context of temperatures and 260 00:17:01,000 --> 00:17:06,000 conditions that are relevant to life? 261 00:17:06,000 --> 00:17:10,000 If you can break a bond at 1000 degrees it doesn't matter because 262 00:17:10,000 --> 00:17:14,000 you cannot have life at that temperature. You've got to be 263 00:17:14,000 --> 00:17:18,000 thinking about a much more restricted temperature sort of range. 264 00:17:18,000 --> 00:17:22,000 So covalent bonds, as most of you know, 265 00:17:22,000 --> 00:17:26,000 this is the principle force that holds atoms together. 266 00:17:26,000 --> 00:17:33,000 It involves a sharing of the 267 00:17:33,000 --> 00:17:38,000 electrons. And an example you can all do in your sleep, 268 00:17:38,000 --> 00:17:43,000 I'm sure. If we take four hydrogen atoms and a carbon atom we can come 269 00:17:43,000 --> 00:17:48,000 up with this molecule which has four covalent bonds. 270 00:17:48,000 --> 00:17:53,000 This is methane. That's the molecule that the cow we 271 00:17:53,000 --> 00:17:59,000 saw the other day burps 400 liters of. 272 00:17:59,000 --> 00:18:04,000 Those are the little bubbles you see coming up when you walk around the 273 00:18:04,000 --> 00:18:10,000 edge of a lake. And it's usually those pairs of 274 00:18:10,000 --> 00:18:16,000 electrons, as you know, that are usually represented like 275 00:18:16,000 --> 00:18:22,000 this. The typical length is about 0. 5 to 0.2 nanometers. 276 00:18:22,000 --> 00:18:28,000 And the important thing about these bonds is these are strong. 277 00:18:28,000 --> 00:18:40,000 It takes about 83 kilocalories per 278 00:18:40,000 --> 00:18:53,000 mole to break a carbon-carbon bond. So at physiologically relevant 279 00:18:53,000 --> 00:19:02,000 temperatures they don't break. They can rotate, 280 00:19:02,000 --> 00:19:07,000 they can stretch and they can bend, but they're not going to break. And 281 00:19:07,000 --> 00:19:12,000 so if you have a carbon-carbon bond in a biological organism it will be 282 00:19:12,000 --> 00:19:16,000 doing this. The carbons will be going this way. 283 00:19:16,000 --> 00:19:21,000 They'll be bending back and forth this way but they won't be breaking. 284 00:19:21,000 --> 00:19:26,000 And to just give you a sense of how far away they are from breaking, 285 00:19:26,000 --> 00:19:31,000 the energy of, say, one of these vibrational modes is about 0. 286 00:19:31,000 --> 00:19:36,000 kilocalories per mole so that you have -- 287 00:19:36,000 --> 00:19:40,000 The average bond is so far away from breaking, even though it's a 288 00:19:40,000 --> 00:19:44,000 distribution, and some are more than others that our molecules stay 289 00:19:44,000 --> 00:19:49,000 together, which is good because we wouldn't want our DNA flying apart 290 00:19:49,000 --> 00:19:53,000 because the covalent bonds were breaking under physiological 291 00:19:53,000 --> 00:19:58,000 conditions. But that also leads us to the need 292 00:19:58,000 --> 00:20:02,000 for one of the things that we'll have to talk about, 293 00:20:02,000 --> 00:20:06,000 which is one of the great secretes of life, is that the metabolism, 294 00:20:06,000 --> 00:20:10,000 all stages of life involve the making and the breaking of bonds. 295 00:20:10,000 --> 00:20:14,000 And you cannot just add a platinum catalyst and put it at 500 degrees 296 00:20:14,000 --> 00:20:18,000 centigrade under a thousand atmospheres of pressure. 297 00:20:18,000 --> 00:20:22,000 All the chemistry that happens in life has to take place in aqueous 298 00:20:22,000 --> 00:20:26,000 solution pretty close to pH 7 at about, you know, 25, 37 299 00:20:26,000 --> 00:20:30,000 degree centigrade. There are a few organisms that can 300 00:20:30,000 --> 00:20:34,000 do it out, but most of it is somewhere around body temperature. 301 00:20:34,000 --> 00:20:37,000 Room temperate is where all that has to take place. 302 00:20:37,000 --> 00:20:41,000 So what you can see is that there had to be some, 303 00:20:41,000 --> 00:20:44,000 in order for life to occur there had to be some invention that would let 304 00:20:44,000 --> 00:20:48,000 bonds be broken and be formed under physiologically relevant conditions. 305 00:20:48,000 --> 00:20:51,000 And those are enzymes. I know most of you have heard of those. 306 00:20:51,000 --> 00:20:55,000 We'll talk about them in a maybe more sublevel, 307 00:20:55,000 --> 00:20:59,000 beyond what some of you have heard anyway. But that -- 308 00:20:59,000 --> 00:21:04,000 Keep in mind now that's the driving force for why we need enzymes, 309 00:21:04,000 --> 00:21:10,000 because covalent bonds are so strong. I also remind you that there are 310 00:21:10,000 --> 00:21:15,000 different types of covalent bonds. That's a single bond. This would 311 00:21:15,000 --> 00:21:21,000 be a double bond or a triple bond. And they get stronger as you share 312 00:21:21,000 --> 00:21:27,000 more electrons. It gets harder and harder to break 313 00:21:27,000 --> 00:21:32,000 them. These are double and triple bonds 314 00:21:32,000 --> 00:21:37,000 called unsaturated bonds. When we talk about unsaturated fats 315 00:21:37,000 --> 00:21:42,000 and things that's because they have double bonds in them. 316 00:21:42,000 --> 00:21:47,000 So olive oil has double bonds in it and beef fat, for example, 317 00:21:47,000 --> 00:21:52,000 doesn't. Other molecules that have double bonds that are important are 318 00:21:52,000 --> 00:21:58,000 oxygen and nitrogen gas, which has got a triple bond. 319 00:21:58,000 --> 00:22:02,000 And when Penny talks to you about the nitrogen cycle this is one of 320 00:22:02,000 --> 00:22:06,000 the really important ones thinking about ecology because we all use 321 00:22:06,000 --> 00:22:10,000 nitrogen, but most organisms including ourselves and most things 322 00:22:10,000 --> 00:22:15,000 on earth cannot break that bond. Yet we all need nitrogen. It has 323 00:22:15,000 --> 00:22:19,000 be what they called fixed, so it's joined to something like 324 00:22:19,000 --> 00:22:23,000 ammonia or nitrite or something like that. And that little fluorescently 325 00:22:23,000 --> 00:22:27,000 labeled bacteria I showed you invading a plant, 326 00:22:27,000 --> 00:22:32,000 we'll see it again, is able to form a symbiosis of plant. 327 00:22:32,000 --> 00:22:36,000 It's one of the few creatures on earth that knows how to break that 328 00:22:36,000 --> 00:22:40,000 bond. And that's why you can get plants that can grow, 329 00:22:40,000 --> 00:22:44,000 like peas and beans and alfalfa and things that can grow without 330 00:22:44,000 --> 00:22:48,000 nitrogen fertilizer. Because they have a little 331 00:22:48,000 --> 00:22:52,000 bacterium who knows how to break that bond and they figured out how 332 00:22:52,000 --> 00:22:56,000 to get together and collaborate in a symbiosis. So these bonds are very 333 00:22:56,000 --> 00:23:00,000 important. So there's another characteristic of these bonds which 334 00:23:00,000 --> 00:23:05,000 is going to be very important for thinking about biology. 335 00:23:05,000 --> 00:23:09,000 And it's known as chirality. And it comes from the fact that our 336 00:23:09,000 --> 00:23:13,000 life on this planet is based on carbon, and carbon's ability to form 337 00:23:13,000 --> 00:23:18,000 remarkable kinds of bonds. And, as you see over there, 338 00:23:18,000 --> 00:23:22,000 carbon forms four bonds. But right now we have to start thinking in 339 00:23:22,000 --> 00:23:26,000 3-dimensional space because carbon is a tetrahedron. Carbon, 340 00:23:26,000 --> 00:23:31,000 four single bonds. And they're in a tetrahedral 341 00:23:31,000 --> 00:23:37,000 arrangement. So if I label them like this, this means it's coming 342 00:23:37,000 --> 00:23:43,000 out of the board, I'm sorry. A, B, C. 343 00:23:43,000 --> 00:23:48,000 And that means it's going back into the board. So if I do a mirror 344 00:23:48,000 --> 00:23:54,000 image, if I looked at what this would look like, 345 00:23:54,000 --> 00:24:00,000 if I could look at its reflection in a mirror, I would see it 346 00:24:00,000 --> 00:24:05,000 would look like this. So these are what are known as 347 00:24:05,000 --> 00:24:10,000 optical isomers. And depending on how you are at 348 00:24:10,000 --> 00:24:14,000 thinking in 3-dimensions this may be obvious to you or it may not be 349 00:24:14,000 --> 00:24:19,000 obvious to you, but you cannot superimpose those. 350 00:24:19,000 --> 00:24:24,000 And this is critical because all through biology there are carbons 351 00:24:24,000 --> 00:24:29,000 that have four different substituents that join to them. 352 00:24:29,000 --> 00:24:33,000 And every time that occurs, biology chooses one of those 353 00:24:33,000 --> 00:24:37,000 arrangements, not the other. And we have sort of a macro way of 354 00:24:37,000 --> 00:24:41,000 perhaps communicating this. So you've been at the party at the 355 00:24:41,000 --> 00:24:46,000 dorm. I was housemaster in McCormick for six years a while back 356 00:24:46,000 --> 00:24:50,000 so I've lived at least in that environment. It's early February, 357 00:24:50,000 --> 00:24:54,000 you're having to go back across the Mass Ave bridge, 358 00:24:54,000 --> 00:24:58,000 it's minus 20 and the wind is whipping along and your 359 00:24:58,000 --> 00:25:02,000 hands are freezing. And you reach into your pocket to 360 00:25:02,000 --> 00:25:06,000 get your gloves and uh-oh, two left gloves. Right there you 361 00:25:06,000 --> 00:25:10,000 have the problem. Biology, as a theme you'll hear 362 00:25:10,000 --> 00:25:14,000 over and over again, is about fitting shapes. 363 00:25:14,000 --> 00:25:18,000 And your hands are mirror images of each other. And you could think of 364 00:25:18,000 --> 00:25:22,000 your gloves as being sort of a receptor. And if the receptor is 365 00:25:22,000 --> 00:25:26,000 designed to take your right hand, take your left hand, I guess, let's 366 00:25:26,000 --> 00:25:30,000 say, you cannot get your right hand into the glove. 367 00:25:30,000 --> 00:25:34,000 It just doesn't fit. And it's at a molecular level. 368 00:25:34,000 --> 00:25:39,000 It's exactly that same thing. So we're going to have to worry as we 369 00:25:39,000 --> 00:25:43,000 go through this about not only how many bonds there are, 370 00:25:43,000 --> 00:25:48,000 but this is why the exact molecular shape, including this optical isomer 371 00:25:48,000 --> 00:25:52,000 issue is going to be very important. There's another very important 372 00:25:52,000 --> 00:25:57,000 principle of covalent bonds that has, again, a huge impact on biology. 373 00:25:57,000 --> 00:26:01,000 And that concerns how the atoms involved in the forming that 374 00:26:01,000 --> 00:26:06,000 covalent bond think about sharing electrons. 375 00:26:06,000 --> 00:26:10,000 In some cases the sharing is pretty much equal, as in a carbon-carbon 376 00:26:10,000 --> 00:26:15,000 bond. That would make sense since it's the same thing on both sides. 377 00:26:15,000 --> 00:26:19,000 Or a carbon-hydrogen bond. The sharing of electrons is pretty much 378 00:26:19,000 --> 00:26:24,000 the same, so the electrons on average are distributed in between 379 00:26:24,000 --> 00:26:29,000 them. And this is what's known as a nonpolar bond. 380 00:26:29,000 --> 00:26:35,000 However, there are important cases of unequal sharing. 381 00:26:35,000 --> 00:26:41,000 And the characteristic of an atom or an element that determines how 382 00:26:41,000 --> 00:26:47,000 this sharing goes is known as electronegativity. 383 00:26:47,000 --> 00:26:53,000 And you could think of this of this as sort of a euphemism for the 384 00:26:53,000 --> 00:26:59,000 greediness of an atom for electrons. 385 00:26:59,000 --> 00:27:03,000 So if you have an oxygen-hydrogen bond, oxygen is more electronegative 386 00:27:03,000 --> 00:27:07,000 than hydrogen. What that means is that although 387 00:27:07,000 --> 00:27:12,000 the electrons are still shared, this is not an ion or anything, the 388 00:27:12,000 --> 00:27:16,000 electrons are shared, there's going to be a little bit of 389 00:27:16,000 --> 00:27:21,000 a negative charge on the oxygen and a little bit of a positive charge on 390 00:27:21,000 --> 00:27:25,000 the hydrogen. And that means you, you know, this will have all sorts 391 00:27:25,000 --> 00:27:30,000 of consequences, as you'll see in a minute. 392 00:27:30,000 --> 00:27:34,000 And there's one important molecule, which if we did the molecular 393 00:27:34,000 --> 00:27:38,000 composition you can see there's a lot of it around, 394 00:27:38,000 --> 00:27:43,000 and that's water. And it's got two OH bonds. And here's where the 395 00:27:43,000 --> 00:27:47,000 structure of water is important, that these two bonds are not 180 396 00:27:47,000 --> 00:27:52,000 degrees opposite to each other. They're 104.5 degrees. So you end 397 00:27:52,000 --> 00:27:56,000 up with a little negative charge here, a little positive charge here, 398 00:27:56,000 --> 00:28:02,000 a little positive charge there. And so every single water molecules 399 00:28:02,000 --> 00:28:08,000 sort of have a negative side and more or less a positive kind of side. 400 00:28:08,000 --> 00:28:14,000 And this has consequences because this means that the water molecules 401 00:28:14,000 --> 00:28:20,000 are going to interact. And to understand that part I need 402 00:28:20,000 --> 00:28:26,000 to introduce you to this second force which we know as the hydrogen 403 00:28:26,000 --> 00:28:35,000 bond. And this is the -- This is a bond that takes place, 404 00:28:35,000 --> 00:28:45,000 that arises because of the slight positive charge of an H bonded to 405 00:28:45,000 --> 00:28:57,000 oxygen or nitrogen -- 406 00:28:57,000 --> 00:28:59,000 -- and the slight negative charge -- 407 00:28:59,000 --> 00:29:09,000 -- of the oxygen or the nitrogen 408 00:29:09,000 --> 00:29:14,000 itself. And right in water we see this be an issue, 409 00:29:14,000 --> 00:29:19,000 because if we have water like this with a couple little bit of positive 410 00:29:19,000 --> 00:29:24,000 charges here and there and a little negative charge here, 411 00:29:24,000 --> 00:29:29,000 and there's another water molecule over here, a little positive charge, 412 00:29:29,000 --> 00:29:34,000 a little negative, a little positive, we can get here what's known 413 00:29:34,000 --> 00:29:42,000 as a hydrogen bond. The hydrogen bond is about 414 00:29:42,000 --> 00:29:53,000 one-twentieth the strength -- 415 00:29:53,000 --> 00:29:57,000 -- of a covalent bond. And that number is really important, 416 00:29:57,000 --> 00:30:01,000 because what that means is that at temperatures that are relevant for 417 00:30:01,000 --> 00:30:05,000 life, not all the molecules will have enough energy to break, 418 00:30:05,000 --> 00:30:09,000 in a population will have enough energy to break that bond. 419 00:30:09,000 --> 00:30:15,000 But some of them will. So hydrogen bonds, let me just 420 00:30:15,000 --> 00:30:21,000 write that down, so at physiologically relevant 421 00:30:21,000 --> 00:30:35,000 temperatures some molecules -- 422 00:30:35,000 --> 00:30:38,000 -- have the energy to break a hydrogen bond. 423 00:30:38,000 --> 00:30:42,000 And we'll talk about it next time. But probably many of you know that 424 00:30:42,000 --> 00:30:46,000 DNA is made of two strands. And the whole principle of copying 425 00:30:46,000 --> 00:30:50,000 the genetic information is you can pull the strands apart and copy the 426 00:30:50,000 --> 00:30:54,000 complimentary information. And we'll spend a lot of time 427 00:30:54,000 --> 00:30:58,000 talking about that. But the relevant thing for the 428 00:30:58,000 --> 00:31:02,000 moment is those two strands, each of which are joined by covalent 429 00:31:02,000 --> 00:31:06,000 bonds, are held together by a whole series of hydrogen bonds between the 430 00:31:06,000 --> 00:31:10,000 different base pairs. And so right there sort of is the 431 00:31:10,000 --> 00:31:14,000 root of why the cells are able to pull those apart, 432 00:31:14,000 --> 00:31:18,000 put them together. And so these hydrogen bonds are 433 00:31:18,000 --> 00:31:22,000 really, really important. And because our life on this planet 434 00:31:22,000 --> 00:31:26,000 is based, we're water-based, and the reason what is such a good 435 00:31:26,000 --> 00:31:31,000 solvent is that it is able to form these hydrogen bonds. 436 00:31:31,000 --> 00:31:34,000 So this is just a little movie showing the hydrogen bonds, 437 00:31:34,000 --> 00:31:38,000 a little simulation of how they can move around and rotate. 438 00:31:38,000 --> 00:31:42,000 The green thing would be the hydrogen bonds here. 439 00:31:42,000 --> 00:31:46,000 This is not really a full representation because the water 440 00:31:46,000 --> 00:31:49,000 molecules are constantly changing partners so they form little cages 441 00:31:49,000 --> 00:31:53,000 and little shells, but they keep forming hydrogen bonds. 442 00:31:53,000 --> 00:31:57,000 They'll break one with one water molecule and immediately reform with 443 00:31:57,000 --> 00:32:01,000 another. This is a simulation that someone did. 444 00:32:01,000 --> 00:32:04,000 It's a picosecond of what would happen to water molecules at zero 445 00:32:04,000 --> 00:32:07,000 degrees centigrade where they're liquid. So, at this point, 446 00:32:07,000 --> 00:32:11,000 they haven't frozen but they're just above that. And you can sort of get 447 00:32:11,000 --> 00:32:14,000 the sense how they're changing partners here. 448 00:32:14,000 --> 00:32:18,000 Here's another simulation done at 100 degrees centigrade. 449 00:32:18,000 --> 00:32:21,000 So this would be a boiling temperature. And what you can see 450 00:32:21,000 --> 00:32:25,000 now is every now and then one of the molecules gets enough energy to 451 00:32:25,000 --> 00:32:28,000 break free of these cages. And that, when you're watching 452 00:32:28,000 --> 00:32:32,000 something boil in a kettle, that, at a molecular level, is 453 00:32:32,000 --> 00:32:36,000 what's happening, is one or another molecule is 454 00:32:36,000 --> 00:32:39,000 finally getting enough energy to break free of this sort of change of 455 00:32:39,000 --> 00:32:43,000 hydrogen bonds that are formed. And it's when we go to think about 456 00:32:43,000 --> 00:32:47,000 how things interact in water, when you dissolve sugar in water or 457 00:32:47,000 --> 00:32:50,000 something in water, you try and dissolve butter in water, 458 00:32:50,000 --> 00:32:54,000 when you stick something into water you have to break a whole lot of 459 00:32:54,000 --> 00:32:58,000 bonds. So there's an energy cost to just simply putting something 460 00:32:58,000 --> 00:33:02,000 into water. And what makes things dissolve or 461 00:33:02,000 --> 00:33:06,000 not is whether once they're in there they can form bonds back again 462 00:33:06,000 --> 00:33:10,000 because water is carbon and hydrogen bonds. There is no polarity. 463 00:33:10,000 --> 00:33:14,000 To get it to dissolve you'd have to break hydrogen bonds. 464 00:33:14,000 --> 00:33:18,000 That costs energy. And it cannot form any because it's only got 465 00:33:18,000 --> 00:33:22,000 nonpolar bonds in the butter so the butter floats around on the water. 466 00:33:22,000 --> 00:33:27,000 But this is really a very, very important force. 467 00:33:27,000 --> 00:33:31,000 And, in fact, you know, this is why when some of the really 468 00:33:31,000 --> 00:33:36,000 interesting properties of water come from. You all know about surface 469 00:33:36,000 --> 00:33:40,000 tension. You've watched little bugs skate around on the surface of the 470 00:33:40,000 --> 00:33:45,000 water. This is the lizard that lives in the rainforest of Central 471 00:33:45,000 --> 00:33:49,000 and South America, and it's about two and a half feet 472 00:33:49,000 --> 00:33:54,000 long. And it can take advantage of this surface tension that's due to 473 00:33:54,000 --> 00:33:59,000 the hydrogen bonding of water to go scooting right across the water. 474 00:33:59,000 --> 00:34:02,000 This is not the greatest of videos. It's what I've managed to find so 475 00:34:02,000 --> 00:34:06,000 far, but you get the idea. It actually runs across the water. 476 00:34:06,000 --> 00:34:09,000 And you're watching the hydrogen bonding in action here. 477 00:34:09,000 --> 00:34:13,000 When I was a grad student my work thesis was on the synthesis of 478 00:34:13,000 --> 00:34:16,000 ribonucleotides, little pieces of RNA. 479 00:34:16,000 --> 00:34:20,000 And I went in a thesis competition. And at the end, where you're 480 00:34:20,000 --> 00:34:23,000 supposed to give a talk about your thesis, and there were four of us, 481 00:34:23,000 --> 00:34:27,000 I thought, well, at least I have a fighting chance. 482 00:34:27,000 --> 00:34:30,000 And when I got in there it turned out one of the other people who was 483 00:34:30,000 --> 00:34:33,000 competing was a guy who studied this lizard, so his talk was full of 484 00:34:33,000 --> 00:34:37,000 movies of these lizards running back and forth across ponds of water. 485 00:34:37,000 --> 00:34:40,000 And I thought I'm dead meat. But it actually turned out I won it, 486 00:34:40,000 --> 00:34:44,000 so I was very surprised. But every time I see something like this it 487 00:34:44,000 --> 00:34:47,000 reminds me of it. OK. And just to remind you, 488 00:34:47,000 --> 00:34:51,000 too, I mean you may not have been thinking of it in this way, 489 00:34:51,000 --> 00:34:54,000 but of course what was all that fuss about when they sent the expeditions 490 00:34:54,000 --> 00:34:58,000 to mars? They were looking for traces of water. 491 00:34:58,000 --> 00:35:02,000 And why is that so important? It's because water has this amazing 492 00:35:02,000 --> 00:35:06,000 capacity to form hydrogen bonds and be the solvent that can let life go. 493 00:35:06,000 --> 00:35:10,000 The moon on triton has methane. All nonpolar bonds, 494 00:35:10,000 --> 00:35:14,000 they're talking about raining methane and rivers of liquid methane 495 00:35:14,000 --> 00:35:18,000 and stuff. You might think about whether it be possible to design a 496 00:35:18,000 --> 00:35:22,000 life form or not or at least what ways things would have to 497 00:35:22,000 --> 00:35:27,000 be different. OK. And we've done enough that I can 498 00:35:27,000 --> 00:35:33,000 quickly now introduce you to our first class of molecules which are 499 00:35:33,000 --> 00:35:39,000 carbohydrates. Julia, would you mind flipping that 500 00:35:39,000 --> 00:35:45,000 light back on for a minute? OK. So carbohydrates have the 501 00:35:45,000 --> 00:35:51,000 general property, general formula. They're CA20. 502 00:35:51,000 --> 00:35:57,000 And you can have different numbers of them. 503 00:35:57,000 --> 00:36:05,000 N-1 carbons have a COH bond. That's known as a hydroxyl group. 504 00:36:05,000 --> 00:36:13,000 And one carbon has a double bond oxygen which is either known as an 505 00:36:13,000 --> 00:36:21,000 aldehyde if it's at the end of a chain or as a ketone if it's in the 506 00:36:21,000 --> 00:36:29,000 middle. And these things can come in different numbers. 507 00:36:29,000 --> 00:36:33,000 So if N equals three it's a triose. If N equals five it's a pentose. 508 00:36:33,000 --> 00:36:38,000 The sugars that you'll see in DNA and RNA are pentoses. 509 00:36:38,000 --> 00:36:43,000 They're five carbon units. A six carbon unit is a hexose. 510 00:36:43,000 --> 00:36:48,000 And a very common hexose that you're all familiar with, 511 00:36:48,000 --> 00:36:53,000 at least familiar with the name of is glucose. And the structure of 512 00:36:53,000 --> 00:36:58,000 glucose in a linear form, if I draw it out here, it's got the 513 00:36:58,000 --> 00:37:03,000 double bond at one end, so it's an aldehyde in that case. 514 00:37:03,000 --> 00:37:07,000 And then there's an OH this way, OH this way, OH, let's see. One, 515 00:37:07,000 --> 00:37:12,000 two, three, four, five, six. OH. And it's just going off the bottom 516 00:37:12,000 --> 00:37:17,000 of the end here, bottom of the board for some of you 517 00:37:17,000 --> 00:37:22,000 probably. But we have hydrogens in the other places. 518 00:37:22,000 --> 00:37:26,000 Now, what I had to do in order to put up this depiction was kind of 519 00:37:26,000 --> 00:37:31,000 flatten this molecule, which you'll know every one of these 520 00:37:31,000 --> 00:37:36,000 is a tetrahedral arrangement. And flatten it down so I could write 521 00:37:36,000 --> 00:37:40,000 it on the board. So there are actually four chiral 522 00:37:40,000 --> 00:37:45,000 centers in a glucose molecule. And, furthermore, although this is 523 00:37:45,000 --> 00:37:49,000 a representation that you can find in textbooks and I can write it on 524 00:37:49,000 --> 00:37:54,000 the board that's not how it appears in nature. What happens is that the 525 00:37:54,000 --> 00:37:58,000 oxygen here comes up and actually cyclizes to this carbon. 526 00:37:58,000 --> 00:38:03,000 And this hydrogen goes and sits up here. 527 00:38:03,000 --> 00:38:07,000 And it gives you, the way glucose is actually found in 528 00:38:07,000 --> 00:38:12,000 solution, this would be what's known as beta-glucose. 529 00:38:12,000 --> 00:38:17,000 And the reason I'm saying beta is we've got a new chiral center that's 530 00:38:17,000 --> 00:38:22,000 formed by this cyclization. And just to give you a sense of 531 00:38:22,000 --> 00:38:27,000 where we are, this is one, two, three, four, five, six going 532 00:38:27,000 --> 00:38:32,000 this way. And over here it's one, 533 00:38:32,000 --> 00:38:36,000 two, three, four, five and six that way. And you can sit there and work 534 00:38:36,000 --> 00:38:40,000 this out yourself afterwards. This is known as a pyranose ring 535 00:38:40,000 --> 00:38:44,000 because it's got, it's actually a six-member ring, 536 00:38:44,000 --> 00:38:49,000 but you can see one of the oxygens is now part of the ring and the 537 00:38:49,000 --> 00:38:53,000 extra carbon is sticking out here. And in solution, because of this 538 00:38:53,000 --> 00:38:57,000 new chiral center, we've now got the possibility of 539 00:38:57,000 --> 00:39:02,000 this thing joining so that the OH is up or the OH is down. 540 00:39:02,000 --> 00:39:05,000 And when it's up, the OH is up, that's known as the 541 00:39:05,000 --> 00:39:09,000 beta form. And if the OH is down, that's known as the alpha form. So, 542 00:39:09,000 --> 00:39:13,000 again, we've got to keep our eyes on all these chiral centers. 543 00:39:13,000 --> 00:39:17,000 This kind of depiction, again, is sort of hard to draw. So, again, 544 00:39:17,000 --> 00:39:21,000 people tend to sort of flatten it out. And you'll see this kind of 545 00:39:21,000 --> 00:39:25,000 representation. You have to realize that this is 546 00:39:25,000 --> 00:39:29,000 approximately the 3-dimensional shape. This is a representation. 547 00:39:29,000 --> 00:39:34,000 Here's beta-glucose there. Every time that you change the 548 00:39:34,000 --> 00:39:39,000 position of one of these hydroxyls, we end up with another sugar. So 549 00:39:39,000 --> 00:39:44,000 this is beta-galactose, sugar with very different properties. 550 00:39:44,000 --> 00:39:50,000 And the difference is here the hydroxyl is up, 551 00:39:50,000 --> 00:39:55,000 here the hydroxyl is down. Two different sugars, two different 552 00:39:55,000 --> 00:40:01,000 properties, but as simple a difference as that. 553 00:40:01,000 --> 00:40:07,000 And then a thing that happens in nature is you can join different 554 00:40:07,000 --> 00:40:13,000 sugar molecules together by a principle that you'll see over and 555 00:40:13,000 --> 00:40:19,000 over again. And that you'll split out a molecule of water and you get 556 00:40:19,000 --> 00:40:25,000 a new covalent bond where this oxygen joins over to the curb and 557 00:40:25,000 --> 00:40:32,000 over here. And what that gives you is galactose beta-1,4 glucose. 558 00:40:32,000 --> 00:40:36,000 This beta-1, 4 glucose is a molecule that you know as lactose 559 00:40:36,000 --> 00:40:44,000 or milk sugar. 560 00:40:44,000 --> 00:40:48,000 And part of the reason we know about it is because in order to metabolize 561 00:40:48,000 --> 00:40:53,000 that you need to have a special enzyme that cuts right here. 562 00:40:53,000 --> 00:40:58,000 That enzyme is known as beta-galactosidase. 563 00:40:58,000 --> 00:41:02,000 That's an enzyme. It's a protein, 564 00:41:02,000 --> 00:41:05,000 which we'll be talking about in the coming lectures, 565 00:41:05,000 --> 00:41:09,000 and it's able to cause this bond to break. And what happens when you 566 00:41:09,000 --> 00:41:12,000 become lactose intolerant is you lose the beta-galactosidase that we 567 00:41:12,000 --> 00:41:15,000 all have as a baby, because we need to be able to eat 568 00:41:15,000 --> 00:41:18,000 milk. And if you don't have it then the lactose passes through your 569 00:41:18,000 --> 00:41:22,000 stomach without getting metabolized. It gets into your intestine and 570 00:41:22,000 --> 00:41:25,000 there are those ten to the fourth bacteria. They metabolize it, 571 00:41:25,000 --> 00:41:28,000 break that bond, and then that causes the gas and discomfort that's 572 00:41:28,000 --> 00:41:32,000 associated with lactose intolerance. 573 00:41:32,000 --> 00:41:36,000 So all the textbooks use lactose as the, beta-galactosidase as the 574 00:41:36,000 --> 00:41:40,000 common enzyme. So the first time I thought that 575 00:41:40,000 --> 00:41:45,000 I'd teach this course I thought, boy, I have a really good idea. I'm 576 00:41:45,000 --> 00:41:49,000 going to come up with a sample enzyme that's different, 577 00:41:49,000 --> 00:41:53,000 but I have to learn what it was. And it was inspired by there's this 578 00:41:53,000 --> 00:41:58,000 product called Beano which is supposed to reduce the side effects 579 00:41:58,000 --> 00:42:02,000 that are commonly associated with eating beans, which probably many of 580 00:42:02,000 --> 00:42:07,000 you are familiar with from summer camps and things. 581 00:42:07,000 --> 00:42:09,000 And the technical term is flatulents. But, in any case, 582 00:42:09,000 --> 00:42:12,000 this was supposed to be something that reduced flatulents. 583 00:42:12,000 --> 00:42:15,000 So I thought it's got to be an enzyme. I know it had something to 584 00:42:15,000 --> 00:42:18,000 do with all of the saccharide s that will change the sugar. 585 00:42:18,000 --> 00:42:21,000 So I looked at the little thing of Beano, and it said Hotline, 586 00:42:21,000 --> 00:42:24,000 any questions call. So I phoned up and said, hi, this is kind of an 587 00:42:24,000 --> 00:42:27,000 unusual question. I'm a college professor and I'm 588 00:42:27,000 --> 00:42:30,000 going to be teaching an introductory biology course. 589 00:42:30,000 --> 00:42:33,000 And I was wondering if I could find out what enzyme you had in Beano and 590 00:42:33,000 --> 00:42:36,000 what it did to what was in the beans. And I said, you know, 591 00:42:36,000 --> 00:42:40,000 it's really sort of an odd question but, you know, 592 00:42:40,000 --> 00:42:43,000 maybe I could talk to one of the scientists in the lab. 593 00:42:43,000 --> 00:42:47,000 And a woman says, hello, Beano. And she listens to me. 594 00:42:47,000 --> 00:42:50,000 And she says, yes, we have a special package we send out to 595 00:42:50,000 --> 00:42:54,000 college professors. And the next thing I knew I got 596 00:42:54,000 --> 00:42:59,000 this huge flood of stuff. So I am now able to quickly tell you 597 00:42:59,000 --> 00:43:05,000 why beans are the musical fruit. And the basis of it is if you join 598 00:43:05,000 --> 00:43:11,000 a glucose and a fructose together by an alpha-1, 2 linkage you get 599 00:43:11,000 --> 00:43:17,000 sucrose. And you all know that's table sugar. We can eat sucrose not 600 00:43:17,000 --> 00:43:23,000 problem. But what beans have is beans have a galactose alpha-1, 601 00:43:23,000 --> 00:43:28,000 6 linkage to sucrose. Or they actually, 602 00:43:28,000 --> 00:43:33,000 sometimes they have two galactose alpha-1, 6 linkages to sucrose and 603 00:43:33,000 --> 00:43:37,000 we cannot metabolize them. And that's sort of related to the 604 00:43:37,000 --> 00:43:42,000 same idea as the glucose intolerance that they go through a stomach, 605 00:43:42,000 --> 00:43:47,000 and then the bacteria know how to break that bond and that causes the 606 00:43:47,000 --> 00:43:51,000 problems that you encountered at summer camp. And so what Beano 607 00:43:51,000 --> 00:43:56,000 turned out to be is it's a sort of low-tech biotech product. 608 00:43:56,000 --> 00:44:01,000 It's a food-grade mold called neurospora. And it's a very, 609 00:44:01,000 --> 00:44:06,000 very crude preparation of an alpha-1, 6 galactosidase. 610 00:44:06,000 --> 00:44:10,000 In other words, an enzyme that can break that 611 00:44:10,000 --> 00:44:14,000 molecule. And once it breaks it you have sucrose, which we can eat, 612 00:44:14,000 --> 00:44:18,000 and galactose, which we know what to do with. And that's the basis of 613 00:44:18,000 --> 00:44:22,000 that. So the very last thing is to talk about polysaccharides. 614 00:44:22,000 --> 00:44:26,000 These come when you join together multiple sugars. 615 00:44:26,000 --> 00:44:30,000 And, as you can appreciate by now, there are many, many ways of joining 616 00:44:30,000 --> 00:44:35,000 sugars together. But suppose we take N glucoses. 617 00:44:35,000 --> 00:44:43,000 There are two common ways they can get joined. They can get joined 618 00:44:43,000 --> 00:44:51,000 together by alpha-1, 4 bonds. And these give a helical 619 00:44:51,000 --> 00:44:59,000 confirmation. And you know these as starch or glycogen. 620 00:44:59,000 --> 00:45:04,000 These are energy storage molecules. And I've run marathons, 621 00:45:04,000 --> 00:45:07,000 some of you may have, but at least you probably know about 622 00:45:07,000 --> 00:45:10,000 carbo-loading. What you're trying to then before 623 00:45:10,000 --> 00:45:14,000 you go is you're eating pasta and everything, which is full of 624 00:45:14,000 --> 00:45:17,000 starches, so it's got polymerized sugars. And you're trying to get 625 00:45:17,000 --> 00:45:20,000 your body to take these in and polymerize them into glycogen so 626 00:45:20,000 --> 00:45:23,000 your liver is as loaded with glycogen before you start the race. 627 00:45:23,000 --> 00:45:26,000 And hitting the wall in a marathon is when you run out of glycogen. 628 00:45:26,000 --> 00:45:30,000 And then you start burning fatty acids and it's no fun at all. 629 00:45:30,000 --> 00:45:34,000 But that's what carbo-loading is all about, is manipulating glucoses that 630 00:45:34,000 --> 00:45:39,000 are in an alpha-1, 4 confirmation, if you just make a 631 00:45:39,000 --> 00:45:43,000 beta-1, 4 confirmation. So the only difference that's 632 00:45:43,000 --> 00:45:48,000 happening in the way we join glucoses together is whether the 633 00:45:48,000 --> 00:45:53,000 hydroxyl is up or down when you join the two of them together. 634 00:45:53,000 --> 00:45:57,000 You get something that's a linear molecule that forms hydrogen bonds 635 00:45:57,000 --> 00:46:02,000 between the sugars. So you have a linear chain of sugars. 636 00:46:02,000 --> 00:46:06,000 And I'm not going to show the details of the hydrogen bond, 637 00:46:06,000 --> 00:46:10,000 but you have one chain going this way and another chain of sugars here. 638 00:46:10,000 --> 00:46:14,000 And you can get hydrogen bonds between them. And you know this as 639 00:46:14,000 --> 00:46:18,000 cellulose. So there are two very important biomolecules that are made 640 00:46:18,000 --> 00:46:22,000 up of glucose. That's just some glucose there. 641 00:46:22,000 --> 00:46:26,000 And if you join them by alpha-1, 4 linkages you get starch, corn 642 00:46:26,000 --> 00:46:31,000 starch, which you've all encountered. 643 00:46:31,000 --> 00:46:35,000 If you join them by hydroxyl in the other direction you get cellulose. 644 00:46:35,000 --> 00:46:39,000 Cellulose is important in biology. It's what plants make their cell 645 00:46:39,000 --> 00:46:44,000 walls of. That's why you can have trees that are so enormously high. 646 00:46:44,000 --> 00:46:48,000 And I guess I'll close with one last. So most of the paper we get 647 00:46:48,000 --> 00:46:53,000 from cellulose is from trees. If you've ever tried and make beer 648 00:46:53,000 --> 00:46:57,000 or wine or something, you probably know you've got to keep 649 00:46:57,000 --> 00:47:02,000 fruit flies away or you're going to get vinegar. 650 00:47:02,000 --> 00:47:07,000 And the reason you get vinegar is that the fruit flies carry on their 651 00:47:07,000 --> 00:47:12,000 feet a bacterium called acidobacteria. 652 00:47:12,000 --> 00:47:17,000 And it likes to live at the surface between the water and the air. 653 00:47:17,000 --> 00:47:22,000 And what it does then, in order to do that is it makes cellulose, 654 00:47:22,000 --> 00:47:27,000 and it floats itself right at the, it makes this great thick mat of 655 00:47:27,000 --> 00:47:32,000 cellulose. And it floats itself right at the air surface interface. 656 00:47:32,000 --> 00:47:36,000 And you can get a mat that's half an inch thick of absolutely perfect 657 00:47:36,000 --> 00:47:41,000 cellulose. And so you don't ever want to see that if you're trying to 658 00:47:41,000 --> 00:47:45,000 make beer or wine or something. But it's a bacterium that's making 659 00:47:45,000 --> 00:47:50,000 this molecule. So you find it in other places 660 00:47:50,000 --> 00:47:53,000 besides trees. So, OK, we'll see you on Monday.