WEBVTT 00:00:00.000 --> 00:00:03.000 Today we're going to start get into at least the nitty-gritty stuff of 00:00:03.000 --> 00:00:07.000 the course. I think a point I want to, just to give you a very broad 00:00:07.000 --> 00:00:10.000 perspective apart from why biology is interesting, 00:00:10.000 --> 00:00:14.000 I want to talk about just very briefly how we study biology. 00:00:14.000 --> 00:00:17.000 I sort of talked about it the other day by sort of the levels at which 00:00:17.000 --> 00:00:21.000 we could do it, from the biosphere all the way down 00:00:21.000 --> 00:00:24.000 to the molecular level. But there is another way of looking 00:00:24.000 --> 00:00:28.000 at it. And I just want to remind you of what I said the other day. 00:00:28.000 --> 00:00:32.000 Biology is an experimental science 00:00:32.000 --> 00:00:38.000 What we know or think we know at the 00:00:38.000 --> 00:00:42.000 moment is because of people having made observations, 00:00:42.000 --> 00:00:45.000 designed hypotheses, tested them and so on. 00:00:45.000 --> 00:00:49.000 And what you're seeing is sort of the sum of the current state of 00:00:49.000 --> 00:00:52.000 human knowledge when I'm talking to you right now. 00:00:52.000 --> 00:00:56.000 There are various, two sort of major disciplines that 00:00:56.000 --> 00:01:00.000 have been used to get at how biological function works. 00:01:00.000 --> 00:01:04.000 As you'll see, the main actor for many of the 00:01:04.000 --> 00:01:08.000 things that happened inside of cells and in living organisms are proteins. 00:01:08.000 --> 00:01:12.000 And we'll be talking about what those are and their structures in 00:01:12.000 --> 00:01:16.000 some detail at the next thing. But the information is not coded in 00:01:16.000 --> 00:01:20.000 the proteins. The information for coding everything that's in a cell 00:01:20.000 --> 00:01:24.000 is in units called genes which are made of, as you probably 00:01:24.000 --> 00:01:27.000 all know, DNA. So there have been, 00:01:27.000 --> 00:01:31.000 classically there were two approaches towards studying biology 00:01:31.000 --> 00:01:34.000 in detailed ways. One was the approach of the 00:01:34.000 --> 00:01:38.000 biochemist who basically took whatever it was, 00:01:38.000 --> 00:01:42.000 put it in a whirling blender or something, and ripped everything 00:01:42.000 --> 00:01:45.000 into little pieces. Sort of like taking the alarm clock 00:01:45.000 --> 00:01:49.000 and shaking it so hard all you've got is all the little bits. 00:01:49.000 --> 00:01:52.000 And once you got it into all little bits then you can purify a little 00:01:52.000 --> 00:01:56.000 thing like a spring or a little wheel or something and try then to 00:01:56.000 --> 00:02:00.000 figure out what that does in the context of the cell. 00:02:00.000 --> 00:02:05.000 You can get very detailed information. And this is in a sort 00:02:05.000 --> 00:02:11.000 of trivial way the science of, discipline of biochemistry. 00:02:11.000 --> 00:02:17.000 Geneticists take a different sort of approach. And what they do is they 00:02:17.000 --> 00:02:23.000 take the living organism and look for a variant where there has just 00:02:23.000 --> 00:02:29.000 been one single change in that whole organism and they study 00:02:29.000 --> 00:02:33.000 its properties. And what you learn from that is 00:02:33.000 --> 00:02:37.000 physiologically relevant information. And if you broke up a car and 00:02:37.000 --> 00:02:41.000 purified the ashtray you could postulate that that was really 00:02:41.000 --> 00:02:45.000 important for the car. But if you made a mutant that was 00:02:45.000 --> 00:02:48.000 missing the ashtray and it still ran, you know, you'd learn that that 00:02:48.000 --> 00:02:52.000 wasn't what was correct. And one of the really powerful 00:02:52.000 --> 00:02:56.000 things that people could only do in very rare instances for a long time 00:02:56.000 --> 00:03:00.000 was to unite the kinds of observations that biochemists made 00:03:00.000 --> 00:03:04.000 with the kinds of observations geneticists made. 00:03:04.000 --> 00:03:08.000 And the explosion in knowledge that's happened over the last couple 00:03:08.000 --> 00:03:12.000 of decades, probably, well, since probably 1975 when 00:03:12.000 --> 00:03:16.000 recombinant DNA came in, was a whole new realm of sort of a 00:03:16.000 --> 00:03:20.000 general discipline we call molecular biology that allowed us to clone 00:03:20.000 --> 00:03:24.000 genes, to sequence them, to many of the things we'll be 00:03:24.000 --> 00:03:27.000 talking about. But one of the real powers in 00:03:27.000 --> 00:03:31.000 looking at this sort of way of thinking about how we study biology 00:03:31.000 --> 00:03:34.000 is that it suddenly enabled one to put these two sorts of things 00:03:34.000 --> 00:03:38.000 together. If you were a biochemist and you purified a protein and you 00:03:38.000 --> 00:03:41.000 found out a chemical property that it had and you wondered what it did 00:03:41.000 --> 00:03:45.000 in the cell, you could sequence the protein and deduce what some of the 00:03:45.000 --> 00:03:49.000 DNA sequence was, find the gene, disable the gene in 00:03:49.000 --> 00:03:52.000 the organism, look and see if your idea was right. 00:03:52.000 --> 00:03:56.000 Or vice versa, if you were a geneticist and you found a mutant 00:03:56.000 --> 00:03:59.000 that had an interesting property and you wondered how it was working then 00:03:59.000 --> 00:04:03.000 you could clone the gene, look at the protein and try and 00:04:03.000 --> 00:04:07.000 figure it out. And that's partly way since about 00:04:07.000 --> 00:04:13.000 1975 there has just been this absolute upheaval in our knowledge 00:04:13.000 --> 00:04:18.000 of biology. And we'll be talking about all of these disciplines here 00:04:18.000 --> 00:04:24.000 as we go through the course. Three or four of you were honest 00:04:24.000 --> 00:04:30.000 enough to say I'd rather be anywhere on earth but in this class. 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 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 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 00:04:40.000 --> 00:04:44.000 life as you go looking forward to moving on with your careers and your 00:04:44.000 --> 00:04:47.000 family and everything else. However, even if you're not 00:04:47.000 --> 00:04:51.000 interested in this course, don't get caught in the trap because 00:04:51.000 --> 00:04:54.000 we're not going to be doing differential equations that it's 00:04:54.000 --> 00:04:58.000 easy. Part of the reason biology is hard is each one of these 00:04:58.000 --> 00:05:02.000 disciplines has a different kind of thinking. 00:05:02.000 --> 00:05:05.000 And to be very effective in biology right now you have to be able to 00:05:05.000 --> 00:05:08.000 think like a chemist, how bonds are formed and broken and 00:05:08.000 --> 00:05:11.000 what's reasonable. You need to be able to think in 00:05:11.000 --> 00:05:15.000 3-dimensional structures because everything happens in 3-D and 00:05:15.000 --> 00:05:18.000 biology is very much about fitting shapes together. 00:05:18.000 --> 00:05:21.000 Genetics is more like probability and statistics. 00:05:21.000 --> 00:05:25.000 Some of those logic games that you sort of used to try and do. 00:05:25.000 --> 00:05:28.000 It's more like that. PCR is, I don't know, recombinant DNA, all 00:05:28.000 --> 00:05:32.000 this sort of stuff is sort of a strategy kind of game. 00:05:32.000 --> 00:05:35.000 So you'll find, as you go through this course, 00:05:35.000 --> 00:05:38.000 that there maybe some things that are easy and some that are difficult. 00:05:38.000 --> 00:05:41.000 But for you, easier or difficult, you'll need to do a lot of different 00:05:41.000 --> 00:05:45.000 thinking. And then, at the moment, you cannot do biology 00:05:45.000 --> 00:05:48.000 anymore by just being a biochemist or just being a geneticist. 00:05:48.000 --> 00:05:51.000 You could in the old days, but now you've got to do it all. 00:05:51.000 --> 00:05:54.000 So where we're going to start right now will be with biochemistry. 00:05:54.000 --> 00:05:58.000 And just before I do that I just want to show you -- 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 00:06:01.000 --> 00:06:04.000 that light on. I think we'll see if we can do this. 00:06:04.000 --> 00:06:07.000 So the green fluorescent protein, thanks, that's great. The green 00:06:07.000 --> 00:06:10.000 fluorescent protein, which we showed you the other day, 00:06:10.000 --> 00:06:13.000 is a protein. And we're going to be talking about that. 00:06:13.000 --> 00:06:16.000 And you'll see it's got structures. You've got these sorts of sheets 00:06:16.000 --> 00:06:19.000 and you'll see little helices. And in a couple of days you'll know 00:06:19.000 --> 00:06:22.000 what this is all about. But I wanted to tell you a couple 00:06:22.000 --> 00:06:26.000 of things just before I get into this. 00:06:26.000 --> 00:06:30.000 This actually was, I showed you that little Barney 00:06:30.000 --> 00:06:34.000 thing to try to emphasize that if you looked at evolution that way, 00:06:34.000 --> 00:06:38.000 you can see most of it was at the level of single cells, 00:06:38.000 --> 00:06:42.000 and that's why things are so common when you get down to the cellular 00:06:42.000 --> 00:06:46.000 and molecular level. I've actually done that demo one 00:06:46.000 --> 00:06:50.000 other place, and that was after, I'm an American Cancer Society 00:06:50.000 --> 00:06:54.000 research professor, and they asked me to give a talk for 00:06:54.000 --> 00:06:58.000 the 50th anniversary of the Illinois Division of the American Cancer 00:06:58.000 --> 00:07:03.000 Society of the importance of basic research. 00:07:03.000 --> 00:07:06.000 And it was after dinner, 500 people in tuxedos and evening 00:07:06.000 --> 00:07:09.000 gowns and bottles of wine, and they kept shortening my time. 00:07:09.000 --> 00:07:12.000 And finally I had ten minutes to get up there in my tux and tell them 00:07:12.000 --> 00:07:16.000 about the importance of research, basic research. And I finally 00:07:16.000 --> 00:07:19.000 decided maybe what I could do is help them understand why when they 00:07:19.000 --> 00:07:22.000 gave money to cure cancer biologists went, ah, signed this one off, 00:07:22.000 --> 00:07:25.000 and studied all these other organisms, fruit flies and 00:07:25.000 --> 00:07:29.000 everything. So I did this little demo. So I was up on the stage at 00:07:29.000 --> 00:07:32.000 the Sheraton holding the Barney and the dinosaur doing what 00:07:32.000 --> 00:07:35.000 you saw me do here. And I thought of briefly about 00:07:35.000 --> 00:07:38.000 putting my tux on just to kind of, you know, give a little zip to the 00:07:38.000 --> 00:07:41.000 extra lecture, but decided not to because I'd get 00:07:41.000 --> 00:07:45.000 chalk all over it or something. So if you think I look stupid doing 00:07:45.000 --> 00:07:48.000 this, you know, my cats thought I was absolutely an 00:07:48.000 --> 00:07:51.000 idiot afterwards. They looked very, 00:07:51.000 --> 00:07:54.000 very puzzled as to what was going on. OK. So I'm going to start talking 00:07:54.000 --> 00:07:57.000 in a couple of minutes about covalent bonds, 00:07:57.000 --> 00:08:00.000 and you're going to roll your eyes upwards and think I've heard about 00:08:00.000 --> 00:08:04.000 that since I was a baby, or some of you will think that. 00:08:04.000 --> 00:08:07.000 But I just want to keep, you've got to understand something 00:08:07.000 --> 00:08:10.000 about how the parts that are used in biology are built or it won't make 00:08:10.000 --> 00:08:13.000 sense. And so just to sort of give you something to sort of keep you 00:08:13.000 --> 00:08:17.000 going here, I want to sort of foreshadow a couple of things that 00:08:17.000 --> 00:08:20.000 are coming. Here's an example of what happens with genetics. 00:08:20.000 --> 00:08:23.000 This is a single mutation in one gene of an individual. 00:08:23.000 --> 00:08:26.000 This woman has what's known as Werner syndrome. 00:08:26.000 --> 00:08:30.000 That's what she looked like as a teenager. 00:08:30.000 --> 00:08:33.000 That's what she looked like at age 48. That's one of these mutations 00:08:33.000 --> 00:08:37.000 that causes advanced aging. And people are working very hard on 00:08:37.000 --> 00:08:40.000 what that, you know, trying to understand aging. 00:08:40.000 --> 00:08:44.000 During your time at MIT, there are going to be some, 00:08:44.000 --> 00:08:47.000 there already have been some amazing discoveries in the last five years, 00:08:47.000 --> 00:08:51.000 and it's going to be a time of explosive growth. 00:08:51.000 --> 00:08:55.000 But that's just one change. And it offers a huge clue as to why 00:08:55.000 --> 00:08:58.000 we age. Here's another example. These are people who have a human 00:08:58.000 --> 00:09:02.000 condition called Xeroderma Pigmentosum. And this was the way 00:09:02.000 --> 00:09:06.000 they used to look before we understood it. 00:09:06.000 --> 00:09:10.000 They have a deficiency in handling damage to their DNA that's caused by 00:09:10.000 --> 00:09:13.000 sunlight. So if they went out in the sunlight once they'd get skin 00:09:13.000 --> 00:09:17.000 cancer. You can see they get skin lesions and everything else. 00:09:17.000 --> 00:09:21.000 It was due to a defect in just one gene. And it took out an important 00:09:21.000 --> 00:09:25.000 kind of DNA repair. Now they know how it works. 00:09:25.000 --> 00:09:29.000 The kids who do this only go out at night. 00:09:29.000 --> 00:09:32.000 They go to summer camp at night. They call them ìChildren of the 00:09:32.000 --> 00:09:35.000 Moonî. They look normal and they don't get skin cancer, 00:09:35.000 --> 00:09:38.000 but they have to live a kind of special life because of this problem. 00:09:38.000 --> 00:09:41.000 And people are working on fixing that. That's the sort of thing that 00:09:41.000 --> 00:09:44.000 can come out genetics. Single change, absolutely dramatic 00:09:44.000 --> 00:09:47.000 affect. You can sort of make inferences that something important 00:09:47.000 --> 00:09:50.000 is broken in that individual because the rest of us don't have this 00:09:50.000 --> 00:09:53.000 problem. The biochemists, you know Watson and Crick, and we'll 00:09:53.000 --> 00:09:56.000 talk more about their structure of DNA. But DNA has to 00:09:56.000 --> 00:10:00.000 get replicated. In fact, just in the last couple 00:10:00.000 --> 00:10:04.000 years we now know that's what's wrong with this person is that 00:10:04.000 --> 00:10:09.000 they're lacking a special DNA copying machine that is able to copy 00:10:09.000 --> 00:10:13.000 over strands of DNA that have damage in them that's caused by sunlight. 00:10:13.000 --> 00:10:17.000 It's got a very sort of flexible active site. It can accommodate the 00:10:17.000 --> 00:10:22.000 bulkiness of this UV induced lesion. And so here's a case where we've 00:10:22.000 --> 00:10:26.000 now united our understanding of that disease at the ultimate biochemical 00:10:26.000 --> 00:10:31.000 molecular level and the high level human syndrome. 00:10:31.000 --> 00:10:35.000 So that's kind of one thing to sort of keep you going. 00:10:35.000 --> 00:10:39.000 OK. So here's a cell. That's the fundamental unit of life. 00:10:39.000 --> 00:10:43.000 I said the other day member cells carry out metabolism. 00:10:43.000 --> 00:10:48.000 They do regulated growth. They do reproduction. That's what 00:10:48.000 --> 00:10:52.000 makes them different from just a bag of proteins and nucleic acids and 00:10:52.000 --> 00:10:56.000 things. And we could think about cells at a couple of 00:10:56.000 --> 00:11:01.000 different levels. We could think about them in terms 00:11:01.000 --> 00:11:06.000 of their atomic composition. I guess we can. Let's see. And if 00:11:06.000 --> 00:11:12.000 we think about it that way it's not particularly exciting. 00:11:12.000 --> 00:11:17.000 Hydrogen is about 60%, oxygen is about 20%, carbon is about 00:11:17.000 --> 00:11:22.000 12%, nitrogen is about 5%, and then there's a whole lot of 00:11:22.000 --> 00:11:28.000 other stuff present at lower levels, phosphorus, sulfate, magnesium, 00:11:28.000 --> 00:11:34.000 manganese, selenium, etc. This isn't a particularly helpful 00:11:34.000 --> 00:11:41.000 way to think about cells. This is perhaps a more useful way, 00:11:41.000 --> 00:11:49.000 and that's to think about it in terms of molecular composition. 00:11:49.000 --> 00:11:56.000 And we're about 80% water. 00:11:56.000 --> 00:12:00.000 Virtually all living organisms, more or less the same, 80% water is 00:12:00.000 --> 00:12:05.000 what our cells are made up of. And of the rest of them, 00:12:05.000 --> 00:12:09.000 there are four major classes of macromolecule, 00:12:09.000 --> 00:12:13.000 large biological molecules that make up the rest of cells. 00:12:13.000 --> 00:12:17.000 And that's what we're going to be focusing on in a little bit. 00:12:17.000 --> 00:12:22.000 There are proteins, which I've already mentioned today, 00:12:22.000 --> 00:12:26.000 and that's about 50% of it. Nucleic acids, that's DNA and RNA, 00:12:26.000 --> 00:12:30.000 we'll say that's about 15%. Carbohydrates, 00:12:30.000 --> 00:12:35.000 which we'll be talking about today. Lipids about 10%. 00:12:35.000 --> 00:12:39.000 And there is a bunch of little stuff that is important but makes up 00:12:39.000 --> 00:12:43.000 the remaining amount. But to understand biology we're 00:12:43.000 --> 00:12:48.000 really going to have to try and figure out how cells work. 00:12:48.000 --> 00:12:52.000 We're going to need to talk about the properties of those molecules. 00:12:52.000 --> 00:12:56.000 And just so you'll know, this picture is actually, 00:12:56.000 --> 00:13:01.000 this was made by somebody at Lawrence Berkeley National Labs. 00:13:01.000 --> 00:13:04.000 As far as I know she still hasn't published it. This is an image of 00:13:04.000 --> 00:13:08.000 an actual cell. It's made by a very fancy technique 00:13:08.000 --> 00:13:12.000 called x-ray tomography where she sort of takes a zillion little sort 00:13:12.000 --> 00:13:15.000 of slices and then assembles the whole thing. This is a yeast cell. 00:13:15.000 --> 00:13:19.000 That purple thing, artificially colored, is the nucleus. 00:13:19.000 --> 00:13:23.000 This thing in the middle is a big storage thing called a vacuole in 00:13:23.000 --> 00:13:27.000 the cell. We cannot see the other cellular components right now, 00:13:27.000 --> 00:13:31.000 but that is a real cell. It looks like a textbook, 00:13:31.000 --> 00:13:35.000 but it's actually a yeast cell that got its picture taken by this very 00:13:35.000 --> 00:13:39.000 fancy thing. So, as I say, we're going to charge 00:13:39.000 --> 00:13:43.000 right now into starting to think about these various molecular forces 00:13:43.000 --> 00:13:47.000 that make possible, that give these various biomolecules 00:13:47.000 --> 00:13:51.000 or biomacromolecules their properties. And I just want to give 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 00:13:55.000 --> 00:13:59.000 couple of lessons, couple of classes. 00:13:59.000 --> 00:14:08.000 They're sort of classes of chemical forces. And today we'll be talking 00:14:08.000 --> 00:14:17.000 about covalent bonds and hydrogen bonds. And we'll go onto to talk 00:14:17.000 --> 00:14:26.000 about other ones in the next class or two. And then we're going to 00:14:26.000 --> 00:14:35.000 talk about these biological macromolecules that I just listed. 00:14:35.000 --> 00:14:40.000 Proteins. Actually, the order we'll be talking about 00:14:40.000 --> 00:14:45.000 them, carbohydrates, nucleic acids, proteins and lipids. 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 00:14:50.000 --> 00:14:56.000 of carbohydrates by just talking about covalent bonds and hydrogen 00:14:56.000 --> 00:15:01.000 bonds. And once we've discussed those we'll go on here and I'll give 00:15:01.000 --> 00:15:05.000 you a couple of examples. And once we've learned some more 00:15:05.000 --> 00:15:08.000 we'll go on and I'll give you some other examples. 00:15:08.000 --> 00:15:11.000 And, as I said, in a second I'm going to say 00:15:11.000 --> 00:15:14.000 covalent bonds. It's going to seem boring. 00:15:14.000 --> 00:15:17.000 Here's just something to sort of keep in, we'll get another one in a 00:15:17.000 --> 00:15:21.000 minute, to look ahead, why do we want to do this sort of 00:15:21.000 --> 00:15:24.000 stuff? I showed you this picture the other day. 00:15:24.000 --> 00:15:27.000 These are E. coli swimming along. Those things I told you are those 00:15:27.000 --> 00:15:30.000 sort of long spiral things are bundles of protein filaments 00:15:30.000 --> 00:15:33.000 called flagella. They're being rotated by a motor at 00:15:33.000 --> 00:15:37.000 the end of the bacterium that's rotating ten to a hundred thousand 00:15:37.000 --> 00:15:41.000 RPM. And that thing is moving at such a rate, so many body lengths a 00:15:41.000 --> 00:15:45.000 second that if it was me moving at that speed I'd be going 300 miles 00:15:45.000 --> 00:15:48.000 per hour that many body lengths. So these are bacteria swimming 00:15:48.000 --> 00:15:52.000 around. The motor that drives them is made of proteins. 00:15:52.000 --> 00:15:56.000 And this is a textbook representation of that motor. 00:15:56.000 --> 00:16:00.000 It has familiar parts to some of you. 00:16:00.000 --> 00:16:03.000 Here's a rotator. There's a bushing. 00:16:03.000 --> 00:16:06.000 There's a drive shaft and so on. It's got parts that you would 00:16:06.000 --> 00:16:09.000 recognize as an engineer, but it's all made out of proteins. 00:16:09.000 --> 00:16:13.000 And that's a textbook diagram. What I want to show you in the next 00:16:13.000 --> 00:16:16.000 slide is they've taken a whole lot of electron micrographic images of 00:16:16.000 --> 00:16:19.000 those things, and the resolution isn't so good, 00:16:19.000 --> 00:16:23.000 but they averaged a whole bunch of them. And this is what it looks 00:16:23.000 --> 00:16:26.000 like. So you can sort of see this really is a machine. It's 00:16:26.000 --> 00:16:30.000 built of proteins. And to understand how these machines 00:16:30.000 --> 00:16:34.000 work you have to understand some of these forces. So that's why I'm 00:16:34.000 --> 00:16:39.000 going to start in and we're going to begin with covalent bonds so that 00:16:39.000 --> 00:16:43.000 we're all on the same page right from the beginning. 00:16:43.000 --> 00:16:48.000 And another aspect, as you'll see, even though you may 00:16:48.000 --> 00:16:52.000 have heard about some of these bonds before, there's a new issue that's 00:16:52.000 --> 00:16:57.000 going to need to occupy your attention. And that is, 00:16:57.000 --> 00:17:01.000 what's the strength of the bond in the context of temperatures and 00:17:01.000 --> 00:17:06.000 conditions that are relevant to life? 00:17:06.000 --> 00:17:10.000 If you can break a bond at 1000 degrees it doesn't matter because 00:17:10.000 --> 00:17:14.000 you cannot have life at that temperature. You've got to be 00:17:14.000 --> 00:17:18.000 thinking about a much more restricted temperature sort of range. 00:17:18.000 --> 00:17:22.000 So covalent bonds, as most of you know, 00:17:22.000 --> 00:17:26.000 this is the principle force that holds atoms together. 00:17:26.000 --> 00:17:33.000 It involves a sharing of the 00:17:33.000 --> 00:17:38.000 electrons. And an example you can all do in your sleep, 00:17:38.000 --> 00:17:43.000 I'm sure. If we take four hydrogen atoms and a carbon atom we can come 00:17:43.000 --> 00:17:48.000 up with this molecule which has four covalent bonds. 00:17:48.000 --> 00:17:53.000 This is methane. That's the molecule that the cow we 00:17:53.000 --> 00:17:59.000 saw the other day burps 400 liters of. 00:17:59.000 --> 00:18:04.000 Those are the little bubbles you see coming up when you walk around the 00:18:04.000 --> 00:18:10.000 edge of a lake. And it's usually those pairs of 00:18:10.000 --> 00:18:16.000 electrons, as you know, that are usually represented like 00:18:16.000 --> 00:18:22.000 this. The typical length is about 0. 5 to 0.2 nanometers. 00:18:22.000 --> 00:18:28.000 And the important thing about these bonds is these are strong. 00:18:28.000 --> 00:18:40.000 It takes about 83 kilocalories per 00:18:40.000 --> 00:18:53.000 mole to break a carbon-carbon bond. So at physiologically relevant 00:18:53.000 --> 00:19:02.000 temperatures they don't break. They can rotate, 00:19:02.000 --> 00:19:07.000 they can stretch and they can bend, but they're not going to break. And 00:19:07.000 --> 00:19:12.000 so if you have a carbon-carbon bond in a biological organism it will be 00:19:12.000 --> 00:19:16.000 doing this. The carbons will be going this way. 00:19:16.000 --> 00:19:21.000 They'll be bending back and forth this way but they won't be breaking. 00:19:21.000 --> 00:19:26.000 And to just give you a sense of how far away they are from breaking, 00:19:26.000 --> 00:19:31.000 the energy of, say, one of these vibrational modes is about 0. 00:19:31.000 --> 00:19:36.000 kilocalories per mole so that you have -- 00:19:36.000 --> 00:19:40.000 The average bond is so far away from breaking, even though it's a 00:19:40.000 --> 00:19:44.000 distribution, and some are more than others that our molecules stay 00:19:44.000 --> 00:19:49.000 together, which is good because we wouldn't want our DNA flying apart 00:19:49.000 --> 00:19:53.000 because the covalent bonds were breaking under physiological 00:19:53.000 --> 00:19:58.000 conditions. But that also leads us to the need 00:19:58.000 --> 00:20:02.000 for one of the things that we'll have to talk about, 00:20:02.000 --> 00:20:06.000 which is one of the great secretes of life, is that the metabolism, 00:20:06.000 --> 00:20:10.000 all stages of life involve the making and the breaking of bonds. 00:20:10.000 --> 00:20:14.000 And you cannot just add a platinum catalyst and put it at 500 degrees 00:20:14.000 --> 00:20:18.000 centigrade under a thousand atmospheres of pressure. 00:20:18.000 --> 00:20:22.000 All the chemistry that happens in life has to take place in aqueous 00:20:22.000 --> 00:20:26.000 solution pretty close to pH 7 at about, you know, 25, 37 00:20:26.000 --> 00:20:30.000 degree centigrade. There are a few organisms that can 00:20:30.000 --> 00:20:34.000 do it out, but most of it is somewhere around body temperature. 00:20:34.000 --> 00:20:37.000 Room temperate is where all that has to take place. 00:20:37.000 --> 00:20:41.000 So what you can see is that there had to be some, 00:20:41.000 --> 00:20:44.000 in order for life to occur there had to be some invention that would let 00:20:44.000 --> 00:20:48.000 bonds be broken and be formed under physiologically relevant conditions. 00:20:48.000 --> 00:20:51.000 And those are enzymes. I know most of you have heard of those. 00:20:51.000 --> 00:20:55.000 We'll talk about them in a maybe more sublevel, 00:20:55.000 --> 00:20:59.000 beyond what some of you have heard anyway. But that -- 00:20:59.000 --> 00:21:04.000 Keep in mind now that's the driving force for why we need enzymes, 00:21:04.000 --> 00:21:10.000 because covalent bonds are so strong. I also remind you that there are 00:21:10.000 --> 00:21:15.000 different types of covalent bonds. That's a single bond. This would 00:21:15.000 --> 00:21:21.000 be a double bond or a triple bond. And they get stronger as you share 00:21:21.000 --> 00:21:27.000 more electrons. It gets harder and harder to break 00:21:27.000 --> 00:21:32.000 them. These are double and triple bonds 00:21:32.000 --> 00:21:37.000 called unsaturated bonds. When we talk about unsaturated fats 00:21:37.000 --> 00:21:42.000 and things that's because they have double bonds in them. 00:21:42.000 --> 00:21:47.000 So olive oil has double bonds in it and beef fat, for example, 00:21:47.000 --> 00:21:52.000 doesn't. Other molecules that have double bonds that are important are 00:21:52.000 --> 00:21:58.000 oxygen and nitrogen gas, which has got a triple bond. 00:21:58.000 --> 00:22:02.000 And when Penny talks to you about the nitrogen cycle this is one of 00:22:02.000 --> 00:22:06.000 the really important ones thinking about ecology because we all use 00:22:06.000 --> 00:22:10.000 nitrogen, but most organisms including ourselves and most things 00:22:10.000 --> 00:22:15.000 on earth cannot break that bond. Yet we all need nitrogen. It has 00:22:15.000 --> 00:22:19.000 be what they called fixed, so it's joined to something like 00:22:19.000 --> 00:22:23.000 ammonia or nitrite or something like that. And that little fluorescently 00:22:23.000 --> 00:22:27.000 labeled bacteria I showed you invading a plant, 00:22:27.000 --> 00:22:32.000 we'll see it again, is able to form a symbiosis of plant. 00:22:32.000 --> 00:22:36.000 It's one of the few creatures on earth that knows how to break that 00:22:36.000 --> 00:22:40.000 bond. And that's why you can get plants that can grow, 00:22:40.000 --> 00:22:44.000 like peas and beans and alfalfa and things that can grow without 00:22:44.000 --> 00:22:48.000 nitrogen fertilizer. Because they have a little 00:22:48.000 --> 00:22:52.000 bacterium who knows how to break that bond and they figured out how 00:22:52.000 --> 00:22:56.000 to get together and collaborate in a symbiosis. So these bonds are very 00:22:56.000 --> 00:23:00.000 important. So there's another characteristic of these bonds which 00:23:00.000 --> 00:23:05.000 is going to be very important for thinking about biology. 00:23:05.000 --> 00:23:09.000 And it's known as chirality. And it comes from the fact that our 00:23:09.000 --> 00:23:13.000 life on this planet is based on carbon, and carbon's ability to form 00:23:13.000 --> 00:23:18.000 remarkable kinds of bonds. And, as you see over there, 00:23:18.000 --> 00:23:22.000 carbon forms four bonds. But right now we have to start thinking in 00:23:22.000 --> 00:23:26.000 3-dimensional space because carbon is a tetrahedron. Carbon, 00:23:26.000 --> 00:23:31.000 four single bonds. And they're in a tetrahedral 00:23:31.000 --> 00:23:37.000 arrangement. So if I label them like this, this means it's coming 00:23:37.000 --> 00:23:43.000 out of the board, I'm sorry. A, B, C. 00:23:43.000 --> 00:23:48.000 And that means it's going back into the board. So if I do a mirror 00:23:48.000 --> 00:23:54.000 image, if I looked at what this would look like, 00:23:54.000 --> 00:24:00.000 if I could look at its reflection in a mirror, I would see it 00:24:00.000 --> 00:24:05.000 would look like this. So these are what are known as 00:24:05.000 --> 00:24:10.000 optical isomers. And depending on how you are at 00:24:10.000 --> 00:24:14.000 thinking in 3-dimensions this may be obvious to you or it may not be 00:24:14.000 --> 00:24:19.000 obvious to you, but you cannot superimpose those. 00:24:19.000 --> 00:24:24.000 And this is critical because all through biology there are carbons 00:24:24.000 --> 00:24:29.000 that have four different substituents that join to them. 00:24:29.000 --> 00:24:33.000 And every time that occurs, biology chooses one of those 00:24:33.000 --> 00:24:37.000 arrangements, not the other. And we have sort of a macro way of 00:24:37.000 --> 00:24:41.000 perhaps communicating this. So you've been at the party at the 00:24:41.000 --> 00:24:46.000 dorm. I was housemaster in McCormick for six years a while back 00:24:46.000 --> 00:24:50.000 so I've lived at least in that environment. It's early February, 00:24:50.000 --> 00:24:54.000 you're having to go back across the Mass Ave bridge, 00:24:54.000 --> 00:24:58.000 it's minus 20 and the wind is whipping along and your 00:24:58.000 --> 00:25:02.000 hands are freezing. And you reach into your pocket to 00:25:02.000 --> 00:25:06.000 get your gloves and uh-oh, two left gloves. Right there you 00:25:06.000 --> 00:25:10.000 have the problem. Biology, as a theme you'll hear 00:25:10.000 --> 00:25:14.000 over and over again, is about fitting shapes. 00:25:14.000 --> 00:25:18.000 And your hands are mirror images of each other. And you could think of 00:25:18.000 --> 00:25:22.000 your gloves as being sort of a receptor. And if the receptor is 00:25:22.000 --> 00:25:26.000 designed to take your right hand, take your left hand, I guess, let's 00:25:26.000 --> 00:25:30.000 say, you cannot get your right hand into the glove. 00:25:30.000 --> 00:25:34.000 It just doesn't fit. And it's at a molecular level. 00:25:34.000 --> 00:25:39.000 It's exactly that same thing. So we're going to have to worry as we 00:25:39.000 --> 00:25:43.000 go through this about not only how many bonds there are, 00:25:43.000 --> 00:25:48.000 but this is why the exact molecular shape, including this optical isomer 00:25:48.000 --> 00:25:52.000 issue is going to be very important. There's another very important 00:25:52.000 --> 00:25:57.000 principle of covalent bonds that has, again, a huge impact on biology. 00:25:57.000 --> 00:26:01.000 And that concerns how the atoms involved in the forming that 00:26:01.000 --> 00:26:06.000 covalent bond think about sharing electrons. 00:26:06.000 --> 00:26:10.000 In some cases the sharing is pretty much equal, as in a carbon-carbon 00:26:10.000 --> 00:26:15.000 bond. That would make sense since it's the same thing on both sides. 00:26:15.000 --> 00:26:19.000 Or a carbon-hydrogen bond. The sharing of electrons is pretty much 00:26:19.000 --> 00:26:24.000 the same, so the electrons on average are distributed in between 00:26:24.000 --> 00:26:29.000 them. And this is what's known as a nonpolar bond. 00:26:29.000 --> 00:26:35.000 However, there are important cases of unequal sharing. 00:26:35.000 --> 00:26:41.000 And the characteristic of an atom or an element that determines how 00:26:41.000 --> 00:26:47.000 this sharing goes is known as electronegativity. 00:26:47.000 --> 00:26:53.000 And you could think of this of this as sort of a euphemism for the 00:26:53.000 --> 00:26:59.000 greediness of an atom for electrons. 00:26:59.000 --> 00:27:03.000 So if you have an oxygen-hydrogen bond, oxygen is more electronegative 00:27:03.000 --> 00:27:07.000 than hydrogen. What that means is that although 00:27:07.000 --> 00:27:12.000 the electrons are still shared, this is not an ion or anything, the 00:27:12.000 --> 00:27:16.000 electrons are shared, there's going to be a little bit of 00:27:16.000 --> 00:27:21.000 a negative charge on the oxygen and a little bit of a positive charge on 00:27:21.000 --> 00:27:25.000 the hydrogen. And that means you, you know, this will have all sorts 00:27:25.000 --> 00:27:30.000 of consequences, as you'll see in a minute. 00:27:30.000 --> 00:27:34.000 And there's one important molecule, which if we did the molecular 00:27:34.000 --> 00:27:38.000 composition you can see there's a lot of it around, 00:27:38.000 --> 00:27:43.000 and that's water. And it's got two OH bonds. And here's where the 00:27:43.000 --> 00:27:47.000 structure of water is important, that these two bonds are not 180 00:27:47.000 --> 00:27:52.000 degrees opposite to each other. They're 104.5 degrees. So you end 00:27:52.000 --> 00:27:56.000 up with a little negative charge here, a little positive charge here, 00:27:56.000 --> 00:28:02.000 a little positive charge there. And so every single water molecules 00:28:02.000 --> 00:28:08.000 sort of have a negative side and more or less a positive kind of side. 00:28:08.000 --> 00:28:14.000 And this has consequences because this means that the water molecules 00:28:14.000 --> 00:28:20.000 are going to interact. And to understand that part I need 00:28:20.000 --> 00:28:26.000 to introduce you to this second force which we know as the hydrogen 00:28:26.000 --> 00:28:35.000 bond. And this is the -- This is a bond that takes place, 00:28:35.000 --> 00:28:45.000 that arises because of the slight positive charge of an H bonded to 00:28:45.000 --> 00:28:57.000 oxygen or nitrogen -- 00:28:57.000 --> 00:28:59.000 -- and the slight negative charge -- 00:28:59.000 --> 00:29:09.000 -- of the oxygen or the nitrogen 00:29:09.000 --> 00:29:14.000 itself. And right in water we see this be an issue, 00:29:14.000 --> 00:29:19.000 because if we have water like this with a couple little bit of positive 00:29:19.000 --> 00:29:24.000 charges here and there and a little negative charge here, 00:29:24.000 --> 00:29:29.000 and there's another water molecule over here, a little positive charge, 00:29:29.000 --> 00:29:34.000 a little negative, a little positive, we can get here what's known 00:29:34.000 --> 00:29:42.000 as a hydrogen bond. The hydrogen bond is about 00:29:42.000 --> 00:29:53.000 one-twentieth the strength -- 00:29:53.000 --> 00:29:57.000 -- of a covalent bond. And that number is really important, 00:29:57.000 --> 00:30:01.000 because what that means is that at temperatures that are relevant for 00:30:01.000 --> 00:30:05.000 life, not all the molecules will have enough energy to break, 00:30:05.000 --> 00:30:09.000 in a population will have enough energy to break that bond. 00:30:09.000 --> 00:30:15.000 But some of them will. So hydrogen bonds, let me just 00:30:15.000 --> 00:30:21.000 write that down, so at physiologically relevant 00:30:21.000 --> 00:30:35.000 temperatures some molecules -- 00:30:35.000 --> 00:30:38.000 -- have the energy to break a hydrogen bond. 00:30:38.000 --> 00:30:42.000 And we'll talk about it next time. But probably many of you know that 00:30:42.000 --> 00:30:46.000 DNA is made of two strands. And the whole principle of copying 00:30:46.000 --> 00:30:50.000 the genetic information is you can pull the strands apart and copy the 00:30:50.000 --> 00:30:54.000 complimentary information. And we'll spend a lot of time 00:30:54.000 --> 00:30:58.000 talking about that. But the relevant thing for the 00:30:58.000 --> 00:31:02.000 moment is those two strands, each of which are joined by covalent 00:31:02.000 --> 00:31:06.000 bonds, are held together by a whole series of hydrogen bonds between the 00:31:06.000 --> 00:31:10.000 different base pairs. And so right there sort of is the 00:31:10.000 --> 00:31:14.000 root of why the cells are able to pull those apart, 00:31:14.000 --> 00:31:18.000 put them together. And so these hydrogen bonds are 00:31:18.000 --> 00:31:22.000 really, really important. And because our life on this planet 00:31:22.000 --> 00:31:26.000 is based, we're water-based, and the reason what is such a good 00:31:26.000 --> 00:31:31.000 solvent is that it is able to form these hydrogen bonds. 00:31:31.000 --> 00:31:34.000 So this is just a little movie showing the hydrogen bonds, 00:31:34.000 --> 00:31:38.000 a little simulation of how they can move around and rotate. 00:31:38.000 --> 00:31:42.000 The green thing would be the hydrogen bonds here. 00:31:42.000 --> 00:31:46.000 This is not really a full representation because the water 00:31:46.000 --> 00:31:49.000 molecules are constantly changing partners so they form little cages 00:31:49.000 --> 00:31:53.000 and little shells, but they keep forming hydrogen bonds. 00:31:53.000 --> 00:31:57.000 They'll break one with one water molecule and immediately reform with 00:31:57.000 --> 00:32:01.000 another. This is a simulation that someone did. 00:32:01.000 --> 00:32:04.000 It's a picosecond of what would happen to water molecules at zero 00:32:04.000 --> 00:32:07.000 degrees centigrade where they're liquid. So, at this point, 00:32:07.000 --> 00:32:11.000 they haven't frozen but they're just above that. And you can sort of get 00:32:11.000 --> 00:32:14.000 the sense how they're changing partners here. 00:32:14.000 --> 00:32:18.000 Here's another simulation done at 100 degrees centigrade. 00:32:18.000 --> 00:32:21.000 So this would be a boiling temperature. And what you can see 00:32:21.000 --> 00:32:25.000 now is every now and then one of the molecules gets enough energy to 00:32:25.000 --> 00:32:28.000 break free of these cages. And that, when you're watching 00:32:28.000 --> 00:32:32.000 something boil in a kettle, that, at a molecular level, is 00:32:32.000 --> 00:32:36.000 what's happening, is one or another molecule is 00:32:36.000 --> 00:32:39.000 finally getting enough energy to break free of this sort of change of 00:32:39.000 --> 00:32:43.000 hydrogen bonds that are formed. And it's when we go to think about 00:32:43.000 --> 00:32:47.000 how things interact in water, when you dissolve sugar in water or 00:32:47.000 --> 00:32:50.000 something in water, you try and dissolve butter in water, 00:32:50.000 --> 00:32:54.000 when you stick something into water you have to break a whole lot of 00:32:54.000 --> 00:32:58.000 bonds. So there's an energy cost to just simply putting something 00:32:58.000 --> 00:33:02.000 into water. And what makes things dissolve or 00:33:02.000 --> 00:33:06.000 not is whether once they're in there they can form bonds back again 00:33:06.000 --> 00:33:10.000 because water is carbon and hydrogen bonds. There is no polarity. 00:33:10.000 --> 00:33:14.000 To get it to dissolve you'd have to break hydrogen bonds. 00:33:14.000 --> 00:33:18.000 That costs energy. And it cannot form any because it's only got 00:33:18.000 --> 00:33:22.000 nonpolar bonds in the butter so the butter floats around on the water. 00:33:22.000 --> 00:33:27.000 But this is really a very, very important force. 00:33:27.000 --> 00:33:31.000 And, in fact, you know, this is why when some of the really 00:33:31.000 --> 00:33:36.000 interesting properties of water come from. You all know about surface 00:33:36.000 --> 00:33:40.000 tension. You've watched little bugs skate around on the surface of the 00:33:40.000 --> 00:33:45.000 water. This is the lizard that lives in the rainforest of Central 00:33:45.000 --> 00:33:49.000 and South America, and it's about two and a half feet 00:33:49.000 --> 00:33:54.000 long. And it can take advantage of this surface tension that's due to 00:33:54.000 --> 00:33:59.000 the hydrogen bonding of water to go scooting right across the water. 00:33:59.000 --> 00:34:02.000 This is not the greatest of videos. It's what I've managed to find so 00:34:02.000 --> 00:34:06.000 far, but you get the idea. It actually runs across the water. 00:34:06.000 --> 00:34:09.000 And you're watching the hydrogen bonding in action here. 00:34:09.000 --> 00:34:13.000 When I was a grad student my work thesis was on the synthesis of 00:34:13.000 --> 00:34:16.000 ribonucleotides, little pieces of RNA. 00:34:16.000 --> 00:34:20.000 And I went in a thesis competition. And at the end, where you're 00:34:20.000 --> 00:34:23.000 supposed to give a talk about your thesis, and there were four of us, 00:34:23.000 --> 00:34:27.000 I thought, well, at least I have a fighting chance. 00:34:27.000 --> 00:34:30.000 And when I got in there it turned out one of the other people who was 00:34:30.000 --> 00:34:33.000 competing was a guy who studied this lizard, so his talk was full of 00:34:33.000 --> 00:34:37.000 movies of these lizards running back and forth across ponds of water. 00:34:37.000 --> 00:34:40.000 And I thought I'm dead meat. But it actually turned out I won it, 00:34:40.000 --> 00:34:44.000 so I was very surprised. But every time I see something like this it 00:34:44.000 --> 00:34:47.000 reminds me of it. OK. And just to remind you, 00:34:47.000 --> 00:34:51.000 too, I mean you may not have been thinking of it in this way, 00:34:51.000 --> 00:34:54.000 but of course what was all that fuss about when they sent the expeditions 00:34:54.000 --> 00:34:58.000 to mars? They were looking for traces of water. 00:34:58.000 --> 00:35:02.000 And why is that so important? It's because water has this amazing 00:35:02.000 --> 00:35:06.000 capacity to form hydrogen bonds and be the solvent that can let life go. 00:35:06.000 --> 00:35:10.000 The moon on triton has methane. All nonpolar bonds, 00:35:10.000 --> 00:35:14.000 they're talking about raining methane and rivers of liquid methane 00:35:14.000 --> 00:35:18.000 and stuff. You might think about whether it be possible to design a 00:35:18.000 --> 00:35:22.000 life form or not or at least what ways things would have to 00:35:22.000 --> 00:35:27.000 be different. OK. And we've done enough that I can 00:35:27.000 --> 00:35:33.000 quickly now introduce you to our first class of molecules which are 00:35:33.000 --> 00:35:39.000 carbohydrates. Julia, would you mind flipping that 00:35:39.000 --> 00:35:45.000 light back on for a minute? OK. So carbohydrates have the 00:35:45.000 --> 00:35:51.000 general property, general formula. They're CA20. 00:35:51.000 --> 00:35:57.000 And you can have different numbers of them. 00:35:57.000 --> 00:36:05.000 N-1 carbons have a COH bond. That's known as a hydroxyl group. 00:36:05.000 --> 00:36:13.000 And one carbon has a double bond oxygen which is either known as an 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 00:36:21.000 --> 00:36:29.000 middle. And these things can come in different numbers. 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. 00:36:33.000 --> 00:36:38.000 The sugars that you'll see in DNA and RNA are pentoses. 00:36:38.000 --> 00:36:43.000 They're five carbon units. A six carbon unit is a hexose. 00:36:43.000 --> 00:36:48.000 And a very common hexose that you're all familiar with, 00:36:48.000 --> 00:36:53.000 at least familiar with the name of is glucose. And the structure of 00:36:53.000 --> 00:36:58.000 glucose in a linear form, if I draw it out here, it's got the 00:36:58.000 --> 00:37:03.000 double bond at one end, so it's an aldehyde in that case. 00:37:03.000 --> 00:37:07.000 And then there's an OH this way, OH this way, OH, let's see. One, 00:37:07.000 --> 00:37:12.000 two, three, four, five, six. OH. And it's just going off the bottom 00:37:12.000 --> 00:37:17.000 of the end here, bottom of the board for some of you 00:37:17.000 --> 00:37:22.000 probably. But we have hydrogens in the other places. 00:37:22.000 --> 00:37:26.000 Now, what I had to do in order to put up this depiction was kind of 00:37:26.000 --> 00:37:31.000 flatten this molecule, which you'll know every one of these 00:37:31.000 --> 00:37:36.000 is a tetrahedral arrangement. And flatten it down so I could write 00:37:36.000 --> 00:37:40.000 it on the board. So there are actually four chiral 00:37:40.000 --> 00:37:45.000 centers in a glucose molecule. And, furthermore, although this is 00:37:45.000 --> 00:37:49.000 a representation that you can find in textbooks and I can write it on 00:37:49.000 --> 00:37:54.000 the board that's not how it appears in nature. What happens is that the 00:37:54.000 --> 00:37:58.000 oxygen here comes up and actually cyclizes to this carbon. 00:37:58.000 --> 00:38:03.000 And this hydrogen goes and sits up here. 00:38:03.000 --> 00:38:07.000 And it gives you, the way glucose is actually found in 00:38:07.000 --> 00:38:12.000 solution, this would be what's known as beta-glucose. 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 00:38:17.000 --> 00:38:22.000 formed by this cyclization. And just to give you a sense of 00:38:22.000 --> 00:38:27.000 where we are, this is one, two, three, four, five, six going 00:38:27.000 --> 00:38:32.000 this way. And over here it's one, 00:38:32.000 --> 00:38:36.000 two, three, four, five and six that way. And you can sit there and work 00:38:36.000 --> 00:38:40.000 this out yourself afterwards. This is known as a pyranose ring 00:38:40.000 --> 00:38:44.000 because it's got, it's actually a six-member ring, 00:38:44.000 --> 00:38:49.000 but you can see one of the oxygens is now part of the ring and the 00:38:49.000 --> 00:38:53.000 extra carbon is sticking out here. And in solution, because of this 00:38:53.000 --> 00:38:57.000 new chiral center, we've now got the possibility of 00:38:57.000 --> 00:39:02.000 this thing joining so that the OH is up or the OH is down. 00:39:02.000 --> 00:39:05.000 And when it's up, the OH is up, that's known as the 00:39:05.000 --> 00:39:09.000 beta form. And if the OH is down, that's known as the alpha form. So, 00:39:09.000 --> 00:39:13.000 again, we've got to keep our eyes on all these chiral centers. 00:39:13.000 --> 00:39:17.000 This kind of depiction, again, is sort of hard to draw. So, again, 00:39:17.000 --> 00:39:21.000 people tend to sort of flatten it out. And you'll see this kind of 00:39:21.000 --> 00:39:25.000 representation. You have to realize that this is 00:39:25.000 --> 00:39:29.000 approximately the 3-dimensional shape. This is a representation. 00:39:29.000 --> 00:39:34.000 Here's beta-glucose there. Every time that you change the 00:39:34.000 --> 00:39:39.000 position of one of these hydroxyls, we end up with another sugar. So 00:39:39.000 --> 00:39:44.000 this is beta-galactose, sugar with very different properties. 00:39:44.000 --> 00:39:50.000 And the difference is here the hydroxyl is up, 00:39:50.000 --> 00:39:55.000 here the hydroxyl is down. Two different sugars, two different 00:39:55.000 --> 00:40:01.000 properties, but as simple a difference as that. 00:40:01.000 --> 00:40:07.000 And then a thing that happens in nature is you can join different 00:40:07.000 --> 00:40:13.000 sugar molecules together by a principle that you'll see over and 00:40:13.000 --> 00:40:19.000 over again. And that you'll split out a molecule of water and you get 00:40:19.000 --> 00:40:25.000 a new covalent bond where this oxygen joins over to the curb and 00:40:25.000 --> 00:40:32.000 over here. And what that gives you is galactose beta-1,4 glucose. 00:40:32.000 --> 00:40:36.000 This beta-1, 4 glucose is a molecule that you know as lactose 00:40:36.000 --> 00:40:44.000 or milk sugar. 00:40:44.000 --> 00:40:48.000 And part of the reason we know about it is because in order to metabolize 00:40:48.000 --> 00:40:53.000 that you need to have a special enzyme that cuts right here. 00:40:53.000 --> 00:40:58.000 That enzyme is known as beta-galactosidase. 00:40:58.000 --> 00:41:02.000 That's an enzyme. It's a protein, 00:41:02.000 --> 00:41:05.000 which we'll be talking about in the coming lectures, 00:41:05.000 --> 00:41:09.000 and it's able to cause this bond to break. And what happens when you 00:41:09.000 --> 00:41:12.000 become lactose intolerant is you lose the beta-galactosidase that we 00:41:12.000 --> 00:41:15.000 all have as a baby, because we need to be able to eat 00:41:15.000 --> 00:41:18.000 milk. And if you don't have it then the lactose passes through your 00:41:18.000 --> 00:41:22.000 stomach without getting metabolized. It gets into your intestine and 00:41:22.000 --> 00:41:25.000 there are those ten to the fourth bacteria. They metabolize it, 00:41:25.000 --> 00:41:28.000 break that bond, and then that causes the gas and discomfort that's 00:41:28.000 --> 00:41:32.000 associated with lactose intolerance. 00:41:32.000 --> 00:41:36.000 So all the textbooks use lactose as the, beta-galactosidase as the 00:41:36.000 --> 00:41:40.000 common enzyme. So the first time I thought that 00:41:40.000 --> 00:41:45.000 I'd teach this course I thought, boy, I have a really good idea. I'm 00:41:45.000 --> 00:41:49.000 going to come up with a sample enzyme that's different, 00:41:49.000 --> 00:41:53.000 but I have to learn what it was. And it was inspired by there's this 00:41:53.000 --> 00:41:58.000 product called Beano which is supposed to reduce the side effects 00:41:58.000 --> 00:42:02.000 that are commonly associated with eating beans, which probably many of 00:42:02.000 --> 00:42:07.000 you are familiar with from summer camps and things. 00:42:07.000 --> 00:42:09.000 And the technical term is flatulents. But, in any case, 00:42:09.000 --> 00:42:12.000 this was supposed to be something that reduced flatulents. 00:42:12.000 --> 00:42:15.000 So I thought it's got to be an enzyme. I know it had something to 00:42:15.000 --> 00:42:18.000 do with all of the saccharide s that will change the sugar. 00:42:18.000 --> 00:42:21.000 So I looked at the little thing of Beano, and it said Hotline, 00:42:21.000 --> 00:42:24.000 any questions call. So I phoned up and said, hi, this is kind of an 00:42:24.000 --> 00:42:27.000 unusual question. I'm a college professor and I'm 00:42:27.000 --> 00:42:30.000 going to be teaching an introductory biology course. 00:42:30.000 --> 00:42:33.000 And I was wondering if I could find out what enzyme you had in Beano and 00:42:33.000 --> 00:42:36.000 what it did to what was in the beans. And I said, you know, 00:42:36.000 --> 00:42:40.000 it's really sort of an odd question but, you know, 00:42:40.000 --> 00:42:43.000 maybe I could talk to one of the scientists in the lab. 00:42:43.000 --> 00:42:47.000 And a woman says, hello, Beano. And she listens to me. 00:42:47.000 --> 00:42:50.000 And she says, yes, we have a special package we send out to 00:42:50.000 --> 00:42:54.000 college professors. And the next thing I knew I got 00:42:54.000 --> 00:42:59.000 this huge flood of stuff. So I am now able to quickly tell you 00:42:59.000 --> 00:43:05.000 why beans are the musical fruit. And the basis of it is if you join 00:43:05.000 --> 00:43:11.000 a glucose and a fructose together by an alpha-1, 2 linkage you get 00:43:11.000 --> 00:43:17.000 sucrose. And you all know that's table sugar. We can eat sucrose not 00:43:17.000 --> 00:43:23.000 problem. But what beans have is beans have a galactose alpha-1, 00:43:23.000 --> 00:43:28.000 6 linkage to sucrose. Or they actually, 00:43:28.000 --> 00:43:33.000 sometimes they have two galactose alpha-1, 6 linkages to sucrose and 00:43:33.000 --> 00:43:37.000 we cannot metabolize them. And that's sort of related to the 00:43:37.000 --> 00:43:42.000 same idea as the glucose intolerance that they go through a stomach, 00:43:42.000 --> 00:43:47.000 and then the bacteria know how to break that bond and that causes the 00:43:47.000 --> 00:43:51.000 problems that you encountered at summer camp. And so what Beano 00:43:51.000 --> 00:43:56.000 turned out to be is it's a sort of low-tech biotech product. 00:43:56.000 --> 00:44:01.000 It's a food-grade mold called neurospora. And it's a very, 00:44:01.000 --> 00:44:06.000 very crude preparation of an alpha-1, 6 galactosidase. 00:44:06.000 --> 00:44:10.000 In other words, an enzyme that can break that 00:44:10.000 --> 00:44:14.000 molecule. And once it breaks it you have sucrose, which we can eat, 00:44:14.000 --> 00:44:18.000 and galactose, which we know what to do with. And that's the basis of 00:44:18.000 --> 00:44:22.000 that. So the very last thing is to talk about polysaccharides. 00:44:22.000 --> 00:44:26.000 These come when you join together multiple sugars. 00:44:26.000 --> 00:44:30.000 And, as you can appreciate by now, there are many, many ways of joining 00:44:30.000 --> 00:44:35.000 sugars together. But suppose we take N glucoses. 00:44:35.000 --> 00:44:43.000 There are two common ways they can get joined. They can get joined 00:44:43.000 --> 00:44:51.000 together by alpha-1, 4 bonds. And these give a helical 00:44:51.000 --> 00:44:59.000 confirmation. And you know these as starch or glycogen. 00:44:59.000 --> 00:45:04.000 These are energy storage molecules. And I've run marathons, 00:45:04.000 --> 00:45:07.000 some of you may have, but at least you probably know about 00:45:07.000 --> 00:45:10.000 carbo-loading. What you're trying to then before 00:45:10.000 --> 00:45:14.000 you go is you're eating pasta and everything, which is full of 00:45:14.000 --> 00:45:17.000 starches, so it's got polymerized sugars. And you're trying to get 00:45:17.000 --> 00:45:20.000 your body to take these in and polymerize them into glycogen so 00:45:20.000 --> 00:45:23.000 your liver is as loaded with glycogen before you start the race. 00:45:23.000 --> 00:45:26.000 And hitting the wall in a marathon is when you run out of glycogen. 00:45:26.000 --> 00:45:30.000 And then you start burning fatty acids and it's no fun at all. 00:45:30.000 --> 00:45:34.000 But that's what carbo-loading is all about, is manipulating glucoses that 00:45:34.000 --> 00:45:39.000 are in an alpha-1, 4 confirmation, if you just make a 00:45:39.000 --> 00:45:43.000 beta-1, 4 confirmation. So the only difference that's 00:45:43.000 --> 00:45:48.000 happening in the way we join glucoses together is whether the 00:45:48.000 --> 00:45:53.000 hydroxyl is up or down when you join the two of them together. 00:45:53.000 --> 00:45:57.000 You get something that's a linear molecule that forms hydrogen bonds 00:45:57.000 --> 00:46:02.000 between the sugars. So you have a linear chain of sugars. 00:46:02.000 --> 00:46:06.000 And I'm not going to show the details of the hydrogen bond, 00:46:06.000 --> 00:46:10.000 but you have one chain going this way and another chain of sugars here. 00:46:10.000 --> 00:46:14.000 And you can get hydrogen bonds between them. And you know this as 00:46:14.000 --> 00:46:18.000 cellulose. So there are two very important biomolecules that are made 00:46:18.000 --> 00:46:22.000 up of glucose. That's just some glucose there. 00:46:22.000 --> 00:46:26.000 And if you join them by alpha-1, 4 linkages you get starch, corn 00:46:26.000 --> 00:46:31.000 starch, which you've all encountered. 00:46:31.000 --> 00:46:35.000 If you join them by hydroxyl in the other direction you get cellulose. 00:46:35.000 --> 00:46:39.000 Cellulose is important in biology. It's what plants make their cell 00:46:39.000 --> 00:46:44.000 walls of. That's why you can have trees that are so enormously high. 00:46:44.000 --> 00:46:48.000 And I guess I'll close with one last. So most of the paper we get 00:46:48.000 --> 00:46:53.000 from cellulose is from trees. If you've ever tried and make beer 00:46:53.000 --> 00:46:57.000 or wine or something, you probably know you've got to keep 00:46:57.000 --> 00:47:02.000 fruit flies away or you're going to get vinegar. 00:47:02.000 --> 00:47:07.000 And the reason you get vinegar is that the fruit flies carry on their 00:47:07.000 --> 00:47:12.000 feet a bacterium called acidobacteria. 00:47:12.000 --> 00:47:17.000 And it likes to live at the surface between the water and the air. 00:47:17.000 --> 00:47:22.000 And what it does then, in order to do that is it makes cellulose, 00:47:22.000 --> 00:47:27.000 and it floats itself right at the, it makes this great thick mat of 00:47:27.000 --> 00:47:32.000 cellulose. And it floats itself right at the air surface interface. 00:47:32.000 --> 00:47:36.000 And you can get a mat that's half an inch thick of absolutely perfect 00:47:36.000 --> 00:47:41.000 cellulose. And so you don't ever want to see that if you're trying to 00:47:41.000 --> 00:47:45.000 make beer or wine or something. But it's a bacterium that's making 00:47:45.000 --> 00:47:50.000 this molecule. So you find it in other places 00:47:50.000 --> 00:47:53.000 besides trees. So, OK, we'll see you on Monday.