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These are the user uploaded subtitles that are being translated: 0 00:00:00,040 --> 00:00:01,540 PROFESSOR: Welcome back. 1 00:00:01,540 --> 00:00:06,390 So, lecture two. 2 00:00:06,390 --> 00:00:08,800 We're going to now dive into our triangle. 3 00:00:08,800 --> 00:00:12,710 As I told you about in the last lecture, the entire course is 4 00:00:12,710 --> 00:00:20,360 organized around our coat of arms, the coat of arms function being 5 00:00:20,360 --> 00:00:22,050 understood two ways. 6 00:00:22,050 --> 00:00:27,855 Biochemistry, genetics. 7 00:00:32,350 --> 00:00:36,080 Fundamentally studying the most interesting and richest molecules, 8 00:00:36,080 --> 00:00:39,330 proteins, but we'll talk about other kinds of molecules. 9 00:00:39,330 --> 00:00:44,280 Genes, the object of study of geneticists, and the 10 00:00:44,280 --> 00:00:46,340 connection of the two. 11 00:00:46,340 --> 00:00:54,360 But today we're going to start with understanding this picture by 12 00:00:54,360 --> 00:00:58,000 beginning several lectures on biochemistry. 13 00:00:58,000 --> 00:00:59,250 All right. 14 00:01:04,402 --> 00:01:05,652 Biochemistry. 15 00:01:08,600 --> 00:01:11,060 Again, you have to put yourself back in the mindset. 16 00:01:11,060 --> 00:01:16,280 To understand how science is done you have to think about what discoveries 17 00:01:16,280 --> 00:01:19,010 meant to the people who were discovering them and what was so 18 00:01:19,010 --> 00:01:20,720 surprising. 19 00:01:20,720 --> 00:01:24,810 So put yourself back in the mindset of somebody just before the turn of the 20 00:01:24,810 --> 00:01:28,510 20th century. 21 00:01:28,510 --> 00:01:31,410 They knew about phenomena. 22 00:01:31,410 --> 00:01:34,560 I'll tell you about a phenomenon that they knew about, that you've 23 00:01:34,560 --> 00:01:36,260 probably heard of. 24 00:01:36,260 --> 00:01:38,576 Fermentation. 25 00:01:38,576 --> 00:01:41,305 A popular subject, for example. 26 00:01:46,990 --> 00:01:49,260 I'll name this section in a moment. 27 00:01:49,260 --> 00:02:02,105 If you take a glass filled with sugar water or fruit juice, and you just 28 00:02:02,105 --> 00:02:07,510 leave it sitting out just at room temperature, over the course of some 29 00:02:07,510 --> 00:02:10,310 days, you'll begin to see bubbles develop. 30 00:02:15,880 --> 00:02:21,470 Sugar water, fruit juice, bubbles develop and come out and you will also 31 00:02:21,470 --> 00:02:28,800 find that if you try to drink it, you've made alcohol. 32 00:02:28,800 --> 00:02:32,790 This is, of course, the basis of beer, wine. 33 00:02:32,790 --> 00:02:35,940 That bit of bubbles is also the basis of bread. 34 00:02:35,940 --> 00:02:39,770 So this is an observation as old as the hills, that if you take sugar 35 00:02:39,770 --> 00:02:43,920 water or fruit juice and you leave it sitting out, you develop bubbles. 36 00:02:43,920 --> 00:02:50,830 The bubbles were known to be carbon dioxide and alcohol came out of it. 37 00:02:50,830 --> 00:02:54,260 And this carbon dioxide drives the production of bread. 38 00:02:54,260 --> 00:02:56,820 That's where you can have bread rise. 39 00:02:56,820 --> 00:02:58,990 And the alcohol. 40 00:02:58,990 --> 00:03:00,330 You get beer, you get wine. 41 00:03:03,025 --> 00:03:06,980 You also had one other very strange thing, another product. 42 00:03:06,980 --> 00:03:10,820 In addition to the production of carbon dioxide and the production of 43 00:03:10,820 --> 00:03:14,535 alcohol, people noticed that the thing got cloudy. 44 00:03:19,860 --> 00:03:25,040 And this is cloudy stuff that also seemed to be produced from this sugar 45 00:03:25,040 --> 00:03:26,845 water was yeast. 46 00:03:30,700 --> 00:03:38,170 For a long time people thought the yeast was a product of fermentation. 47 00:03:38,170 --> 00:03:40,050 They didn't know that yeast was a living organism. 48 00:03:40,050 --> 00:03:41,510 They didn't know it was a cell. 49 00:03:41,510 --> 00:03:43,630 They thought it was a product of fermentation. 50 00:03:43,630 --> 00:03:47,740 And it took some pretty clever science to show that the yeast was not a 51 00:03:47,740 --> 00:03:51,990 result of fermentation, it was the cause of the fermentation. 52 00:03:51,990 --> 00:03:56,050 Because there was a little bit of yeast there, it produces fermentation 53 00:03:56,050 --> 00:03:59,360 and it grows and divides and makes more and more yeast cells, and the 54 00:03:59,360 --> 00:04:02,000 yeast is the cause. 55 00:04:02,000 --> 00:04:06,570 So Pasteur was involved in showing that you needed living organisms there 56 00:04:06,570 --> 00:04:08,980 in order to produce the fermentation. 57 00:04:08,980 --> 00:04:11,640 Fermentation, ferment, from the Latin [LATIN] 58 00:04:11,640 --> 00:04:12,330 to boil. 59 00:04:12,330 --> 00:04:14,520 The bubbles coming off there. 60 00:04:14,520 --> 00:04:15,770 Really cool stuff. 61 00:04:18,529 --> 00:04:24,070 The problem was they got into their heads so solidly that you needed this 62 00:04:24,070 --> 00:04:30,820 living organism yeast to do the fermentation that people began to ask, 63 00:04:30,820 --> 00:04:34,310 was this something only living matter could do? 64 00:04:34,310 --> 00:04:37,650 Now the chemists at the time, in the 1700s and the 65 00:04:37,650 --> 00:04:38,830 1800s, were really curious. 66 00:04:38,830 --> 00:04:39,690 This looked like chemistry. 67 00:04:39,690 --> 00:04:43,770 You were taking sugar, you were producing carbon dioxide and alcohols. 68 00:04:43,770 --> 00:04:45,830 How could this be made to work? 69 00:04:45,830 --> 00:04:48,220 Did you need a living organism to do it? 70 00:04:48,220 --> 00:04:54,390 People worked really hard to try to somehow extract from the living 71 00:04:54,390 --> 00:04:58,030 organism something capable of doing fermentation 72 00:04:58,030 --> 00:05:00,100 without a living organism. 73 00:05:00,100 --> 00:05:02,790 And they failed miserably. 74 00:05:02,790 --> 00:05:03,760 Miserably. 75 00:05:03,760 --> 00:05:10,000 They tried sodium hydroxide treatment of this yeast and see if they could 76 00:05:10,000 --> 00:05:10,930 extract things. 77 00:05:10,930 --> 00:05:14,140 They tried boiling it at high temperatures to extract things. 78 00:05:14,140 --> 00:05:19,620 They tried letting it sit for days and then whatever they did the resulting 79 00:05:19,620 --> 00:05:25,290 goop that they got could not do fermentation. 80 00:05:25,290 --> 00:05:28,950 You might now guess that the reason they couldn't do fermentation is they 81 00:05:28,950 --> 00:05:31,990 had managed, with their harsh treatment of high temperatures and 82 00:05:31,990 --> 00:05:35,760 sodium hydroxide and other things like that, to have destroyed that which 83 00:05:35,760 --> 00:05:37,020 might carry out fermentation. 84 00:05:37,020 --> 00:05:40,060 But that was not the conclusion in the late 1800s. 85 00:05:40,060 --> 00:05:44,860 The conclusion was that fermentation, this miraculous transformation that 86 00:05:44,860 --> 00:05:50,920 life could carry out, was inherently only possible because of a living 87 00:05:50,920 --> 00:05:51,930 organism being present. 88 00:05:51,930 --> 00:05:57,730 It was inherently necessary to have living protoplasm to do this. 89 00:05:57,730 --> 00:06:00,540 It was not chemistry, it was beyond chemistry. 90 00:06:00,540 --> 00:06:03,290 It was some vitalism. 91 00:06:03,290 --> 00:06:06,520 And it was referred to as vital forces, vitalism, the idea that in 92 00:06:06,520 --> 00:06:09,230 addition to the laws of physics and the laws of chemistry there were these 93 00:06:09,230 --> 00:06:14,300 other properties that life had that couldn't be understood as chemistry. 94 00:06:14,300 --> 00:06:18,680 And that was pretty much the view up until the 1890s. 95 00:06:18,680 --> 00:06:23,640 As late as the 1890s this idea that there was some magic living things 96 00:06:23,640 --> 00:06:27,300 could do was still holding sway. 97 00:06:27,300 --> 00:06:30,600 That was called vitalism, this concept. 98 00:06:34,130 --> 00:06:40,010 And what I want to start talking about is the death of vitalism. 99 00:06:44,600 --> 00:06:50,490 It turns out that vitalism came because nobody could manage to get 100 00:06:50,490 --> 00:06:54,120 something that could do this fermentation. 101 00:06:54,120 --> 00:06:57,790 If you could somehow show that you could extract the thing that could 102 00:06:57,790 --> 00:07:00,820 ferment without the need of the organism, that would be a big deal. 103 00:07:03,970 --> 00:07:13,360 A guy called Eduard Buchner came along and, for a variety of reasons I won't 104 00:07:13,360 --> 00:07:19,850 go into, but in the mid-1890s said, you know, maybe we should try to be a 105 00:07:19,850 --> 00:07:22,910 little more gentle with this yeast thing. 106 00:07:22,910 --> 00:07:27,470 And, as so often happens in science, it was technology that drove it. 107 00:07:27,470 --> 00:07:31,280 He invented powerful new technology. 108 00:07:31,280 --> 00:07:35,850 He invented this powerful technology right here. 109 00:07:35,850 --> 00:07:43,140 The powerful technology that he invented was first this thing here. 110 00:07:43,140 --> 00:07:49,390 A long mortar hanging and a little pestle here in which he could put the 111 00:07:49,390 --> 00:07:56,370 yeast, add some sand, some quartz, little particles of sand, and swing 112 00:07:56,370 --> 00:07:58,820 this thing around very gently. 113 00:07:58,820 --> 00:08:03,920 And the little sand would crack open the yeast and the yeast would become 114 00:08:03,920 --> 00:08:08,910 kind of a doughy, gray, mushy mixture. 115 00:08:08,910 --> 00:08:11,600 And he only did that for a couple of minutes, just going around and around 116 00:08:11,600 --> 00:08:12,450 and around. 117 00:08:12,450 --> 00:08:17,360 Then what he did was he scooped it off and he put it in a piece of canvas. 118 00:08:17,360 --> 00:08:21,210 And he covered canvas up into a little package and he stuffed 119 00:08:21,210 --> 00:08:22,835 it into this press. 120 00:08:22,835 --> 00:08:28,620 And he turns to press and squeezes out yeast juice. 121 00:08:31,620 --> 00:08:38,610 And remarkably, the yeast juice was able to carry out fermentation. 122 00:08:38,610 --> 00:08:42,120 Now he had to convince people that it wasn't that a whole lot of cells had 123 00:08:42,120 --> 00:08:43,610 somehow gotten in the yeast juice. 124 00:08:43,610 --> 00:08:46,800 So he had to convince people that there weren't cells there. 125 00:08:46,800 --> 00:08:50,390 And he showed there really weren't cells there, or not very many cells. 126 00:08:50,390 --> 00:08:53,290 And even a few cells getting in wouldn't be a problem, 127 00:08:53,290 --> 00:08:54,290 because it was so active. 128 00:08:54,290 --> 00:08:57,175 It was doing so much fermentation it couldn't be accounted for by a couple 129 00:08:57,175 --> 00:08:58,320 little strays cells. 130 00:08:58,320 --> 00:09:00,450 So he had to be very scientific about it. 131 00:09:00,450 --> 00:09:11,810 But he eventually publishes in 1897 that this yeast juice can carry out 132 00:09:11,810 --> 00:09:13,060 fermentation. 133 00:09:21,270 --> 00:09:26,760 The stuff that carried out fermentation was referred to as, you 134 00:09:26,760 --> 00:09:28,700 know, something from yeast. 135 00:09:28,700 --> 00:09:33,260 The Latin name here referring to yeast is zyme. 136 00:09:33,260 --> 00:09:36,690 The thing that was in yeast was called an enzyme. 137 00:09:39,590 --> 00:09:41,690 There were enzymes. 138 00:09:41,690 --> 00:09:42,920 Something in yeast. 139 00:09:42,920 --> 00:09:45,460 They didn't quite know what it was. 140 00:09:45,460 --> 00:09:51,070 And these enzyme or enzymes could carry out this miraculous 141 00:09:51,070 --> 00:09:53,800 transformation. 142 00:09:53,800 --> 00:09:59,380 Well, Buchner like knocked everybody's socks off with this. 143 00:09:59,380 --> 00:10:05,050 And, amongst other things, Buchner wins the Nobel prize 144 00:10:05,050 --> 00:10:07,110 for this for chemistry. 145 00:10:07,110 --> 00:10:13,300 Nobel prize in chemistry for the year in 1907. 146 00:10:13,300 --> 00:10:17,830 One of the first Nobel prizes, the seventh Nobel prize given in chemistry 147 00:10:17,830 --> 00:10:21,320 goes to Buchner for this landmark thing. 148 00:10:21,320 --> 00:10:29,560 Now, I got to say, this whole notion is so remarkable that I went back and 149 00:10:29,560 --> 00:10:35,060 pulled out Buchner's Nobel lecture 1907 in which when he gets invited to 150 00:10:35,060 --> 00:10:38,960 Sweden on December 10 for Alfred Nobel's birthday and gives a 151 00:10:38,960 --> 00:10:40,550 talk and all that. 152 00:10:40,550 --> 00:10:41,590 It's still so cool. 153 00:10:41,590 --> 00:10:45,350 And we have on the web in the resource box associated with the course 154 00:10:45,350 --> 00:10:46,700 Buchner's lecture. 155 00:10:46,700 --> 00:10:50,120 I'm just going to read you a little bit from the end of Buchner's lecture. 156 00:10:50,120 --> 00:10:54,060 Because on the one hand he's so excited that they understand this, and 157 00:10:54,060 --> 00:10:58,620 on the other hand he realizes, boy, we hardly know anything. 158 00:10:58,620 --> 00:11:01,610 Like, I can't tell you what these enzymes are at all. 159 00:11:01,610 --> 00:11:03,800 We've managed to show that yeast juice can do this. 160 00:11:03,800 --> 00:11:05,380 We don't need a living organism. 161 00:11:05,380 --> 00:11:06,870 Vitalism isn't right. 162 00:11:06,870 --> 00:11:08,880 But boy, I have no clue what's going on. 163 00:11:08,880 --> 00:11:10,080 And so honest here. 164 00:11:10,080 --> 00:11:11,490 It's wonderful. 165 00:11:11,490 --> 00:11:15,390 "Distinguished audience," he says in his closing remarks, "as you'll see, 166 00:11:15,390 --> 00:11:19,500 we are still far from an understanding of the processes involved in alcohol 167 00:11:19,500 --> 00:11:24,390 fermentation of sugar, as well as from a more detailed description of the 168 00:11:24,390 --> 00:11:28,880 nature of the zymes" which he also was using for enzyme. 169 00:11:28,880 --> 00:11:32,390 "Quite the contrary, every step we take the present leads to fresh 170 00:11:32,390 --> 00:11:34,170 complications. 171 00:11:34,170 --> 00:11:39,780 We must be thankful, however, if the increasingly narrow and steep paths do 172 00:11:39,780 --> 00:11:44,580 not end in an unclimbable cliff." He had no idea that they'd ever be able 173 00:11:44,580 --> 00:11:46,540 to understand what these enzymes were about. 174 00:11:46,540 --> 00:11:50,450 He goes on for a little bit, and he says, "Nevertheless, there is no cause 175 00:11:50,450 --> 00:11:52,740 for discouragement. 176 00:11:52,740 --> 00:11:56,180 The progress made in the field of fermentation processes is clearly 177 00:11:56,180 --> 00:11:59,530 revealed when you compare our present knowledge with that of just a few 178 00:11:59,530 --> 00:12:01,680 decades ago. 179 00:12:01,680 --> 00:12:06,210 The differences between the vitalistic view and the enzyme theory have been 180 00:12:06,210 --> 00:12:08,540 reconciled. 181 00:12:08,540 --> 00:12:13,710 The fermentation process becomes comprehensible to us now that it is 182 00:12:13,710 --> 00:12:17,870 possible to separate it from the rest of the processes of life. 183 00:12:17,870 --> 00:12:21,460 Just as the first step toward the explanation of the phenomenon of 184 00:12:21,460 --> 00:12:25,290 combustion rested on the fact that it was possible to separate the 185 00:12:25,290 --> 00:12:29,930 generation of light and heat from the processes of oxidation." He's thinking 186 00:12:29,930 --> 00:12:32,250 about this in a very broad sense. 187 00:12:32,250 --> 00:12:37,100 And he says, "We are seeing the cells of plants and animals more and more 188 00:12:37,100 --> 00:12:41,350 clearly as chemical factories where the various products are manufactured 189 00:12:41,350 --> 00:12:45,430 in separate workshops." A very industrial revolution 190 00:12:45,430 --> 00:12:46,590 kind if view here. 191 00:12:46,590 --> 00:12:51,820 "The enzymes act as the overseers." What a factory view of 192 00:12:51,820 --> 00:12:54,350 the late 1800s here. 193 00:12:54,350 --> 00:12:57,320 "Our acquaintance with these most important agents of living things is 194 00:12:57,320 --> 00:12:58,480 constantly increasing. 195 00:12:58,480 --> 00:13:02,800 Even though we may still be a long way from our goal, we are approaching it 196 00:13:02,800 --> 00:13:03,750 step by step. 197 00:13:03,750 --> 00:13:06,210 Everything is justifying our hopes. 198 00:13:06,210 --> 00:13:09,950 We must never therefore let ourselves fall into the way of thinking 199 00:13:09,950 --> 00:13:13,070 ignorabimus, we shall never know. 200 00:13:13,070 --> 00:13:17,810 But we must have every confidence that the day will dawn with even those 201 00:13:17,810 --> 00:13:22,210 processes of life, which are still a puzzle today, will cease to be 202 00:13:22,210 --> 00:13:26,490 inaccessible to us natural scientists." 203 00:13:26,490 --> 00:13:28,920 That's one hell of a way to end a Nobel lecture. 204 00:13:28,920 --> 00:13:33,270 And it's a statement about what is amazing about science was that it all 205 00:13:33,270 --> 00:13:37,820 seemed unimaginable that we were ever going to understand what those enzymes 206 00:13:37,820 --> 00:13:41,570 were about at essentially the turn of the 20th century. 207 00:13:41,570 --> 00:13:44,540 And of course you know perfectly well we do know, and we're going to cover 208 00:13:44,540 --> 00:13:47,230 in the next couple of lectures what all of that is about. 209 00:13:47,230 --> 00:13:51,440 And all the things we don't understand today, you can just apply Buchner to 210 00:13:51,440 --> 00:13:52,610 that as well. 211 00:13:52,610 --> 00:13:55,310 So all right, that's where we are. 212 00:13:55,310 --> 00:13:59,270 Buchner the death of vitalism, and now we've got actually dive in and 213 00:13:59,270 --> 00:14:01,860 understand how all that stuff works. 214 00:14:01,860 --> 00:14:03,050 What are those enzymes? 215 00:14:03,050 --> 00:14:07,570 Can we understand these amazing properties of life? 216 00:14:07,570 --> 00:14:11,210 Properties of being able to carry out chemical transformations, properties 217 00:14:11,210 --> 00:14:13,720 of being able to, oh, I don't know, even more simple things. 218 00:14:13,720 --> 00:14:15,650 Having cells in the first place. 219 00:14:15,650 --> 00:14:17,750 Membranes around cells. 220 00:14:17,750 --> 00:14:19,310 How in the world you do that? 221 00:14:19,310 --> 00:14:21,860 Like, what makes a membrane the divides a cell's 222 00:14:21,860 --> 00:14:23,200 inside from its outside? 223 00:14:23,200 --> 00:14:24,690 How you do other sorts of things? 224 00:14:24,690 --> 00:14:28,825 Can we understand all of those things in terms of fundamental chemistry? 225 00:14:28,825 --> 00:14:31,280 That's what biochemistry's asking us here. 226 00:14:31,280 --> 00:14:33,430 So before we go on to the next segment, test 227 00:14:33,430 --> 00:14:34,680 yourself with this problem. 19254

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