WEBVTT 00:00:01.000 --> 00:00:04.000 OK. So today we're going to spend a little bit of time on some 00:00:04.000 --> 00:00:08.000 elementary chemistry just to develop our language that we use with one 00:00:08.000 --> 00:00:12.000 another. And so when I say hydrogen bond, you don't stare blankly at me 00:00:12.000 --> 00:00:16.000 and scratch your heads. Many of you have had this already. 00:00:16.000 --> 00:00:20.000 For many of you this is a review, but it's a useful review. 00:00:20.000 --> 00:00:24.000 We believe here at MIT of teaching things two or three times often, 00:00:24.000 --> 00:00:29.000 the same subject matter, but at increasing levels of sophistication. 00:00:29.000 --> 00:00:35.000 So I do this without apology. Our first issue here is how are 00:00:35.000 --> 00:00:41.000 atoms and molecules held together? And the most familiar way by which 00:00:41.000 --> 00:00:48.000 atoms and molecules are held together is, of course, 00:00:48.000 --> 00:00:54.000 the covalent bonds. And covalent bonds have an energy of roughly 80 00:00:54.000 --> 00:01:00.000 kilocalories per mole. And that's a rather strong energy to 00:01:00.000 --> 00:01:05.000 hold together two atoms because the energy, the thermal energy, 00:01:05.000 --> 00:01:10.000 that is the energy at, let's say, body temperature is about 0.6 00:01:10.000 --> 00:01:14.000 kilocalories per mole. And, therefore, if you had a bond, 00:01:14.000 --> 00:01:19.000 if there was something holding things together that was in this 00:01:19.000 --> 00:01:24.000 range or two or three or four times higher then the simple thermal 00:01:24.000 --> 00:01:29.000 energy at room temperature or at body temperature would be sufficient 00:01:29.000 --> 00:01:34.000 to break apart such a bond. But, in fact, this energy, 00:01:34.000 --> 00:01:38.000 the energy of a covalent bond is so much higher that it's highly 00:01:38.000 --> 00:01:43.000 unlikely that thermal energy is going to break apart a preexisting 00:01:43.000 --> 00:01:48.000 covalent bond. And I was just reading yesterday 00:01:48.000 --> 00:01:52.000 about how people were analyzing the mitochondrial DNA from some 00:01:52.000 --> 00:01:57.000 Neanderthal bones which were dug up. The last Neanderthal lived around 00:01:57.000 --> 00:02:02.000 30,000 years ago, our recently demised cousins. 00:02:02.000 --> 00:02:06.000 And they were analyzing the DNA sequences. And they got out of 00:02:06.000 --> 00:02:11.000 those analyses stretches of DNA that were 200, 300 nucleotides long. 00:02:11.000 --> 00:02:15.000 And that really is stunning testimonial to the fact that under 00:02:15.000 --> 00:02:20.000 very difficult conditions, nonetheless, complex biological 00:02:20.000 --> 00:02:24.000 molecules are able to survive over astounding periods of time, 00:02:24.000 --> 00:02:29.000 indeed those that are held together by the covalent bonds like this. 00:02:29.000 --> 00:02:33.000 Of course, you remember the film Jurassic Park where they used PCR 00:02:33.000 --> 00:02:37.000 reaction to resurrect the DNA of dinosaurs. That's a bit of a 00:02:37.000 --> 00:02:42.000 fantasy since dinosaurs left us, I guess, about 150 million years ago, 00:02:42.000 --> 00:02:46.000 something like that. There's a big difference, 00:02:46.000 --> 00:02:51.000 obviously, between 300,000 and 150 million year ago. 00:02:51.000 --> 00:02:55.000 Now, the fact is if you look at the way that molecules are actually 00:02:55.000 --> 00:03:00.000 hooked up, for instance, let's look at a water molecule here. 00:03:00.000 --> 00:03:04.000 Ideally there should be no charge on this molecule. 00:03:04.000 --> 00:03:08.000 And, in fact, there is no net charge. But the truth of the matter 00:03:08.000 --> 00:03:13.000 is, if one wants to get frank, that oxygen molecules, and we always 00:03:13.000 --> 00:03:17.000 are here, that oxygen molecules have a greater affinity for electrons 00:03:17.000 --> 00:03:22.000 than do hydrogen atoms, i.e., they are electronegative. 00:03:22.000 --> 00:03:26.000 And, therefore, what this means is that the swarms of electrons that 00:03:26.000 --> 00:03:31.000 are holding all this together at the orbitals are drawn more closely to 00:03:31.000 --> 00:03:35.000 the oxygen and the hydrogen atoms, i.e., the protons are relatively 00:03:35.000 --> 00:03:40.000 willing to give up their electrons. And what this means is that there's 00:03:40.000 --> 00:03:44.000 an unequal distribution. And, as a consequence, there is a 00:03:44.000 --> 00:03:48.000 fraction of a negative charge here at this end of the molecule and 00:03:48.000 --> 00:03:52.000 there are fractions of positive charges here because it's not as if 00:03:52.000 --> 00:03:56.000 they've totally given up the electrons, but the electrons are 00:03:56.000 --> 00:03:59.000 shifted more in this direction. And this molecule is therefore 00:03:59.000 --> 00:04:03.000 called a polar molecule by virtue of the fact that here it has a positive 00:04:03.000 --> 00:04:07.000 pole and here it has a negative pole. There are other pairs of molecules 00:04:07.000 --> 00:04:10.000 which are relatively equally electronegative. 00:04:10.000 --> 00:04:14.000 For example, here, if we have a carbon and a hydrogen, 00:04:14.000 --> 00:04:18.000 these two atoms are roughly equally matched in terms of their ability to 00:04:18.000 --> 00:04:22.000 pull electrons away, one from the other. And, 00:04:22.000 --> 00:04:25.000 as a consequence, there is no net shifting of charge. 00:04:25.000 --> 00:04:29.000 And keep in mind that this delta I show here is only a fraction of an 00:04:29.000 --> 00:04:33.000 electronic charge. It's not the entire electronic 00:04:33.000 --> 00:04:37.000 charge moved over. But this has important consequences 00:04:37.000 --> 00:04:41.000 for the entire biochemistry that we're about to get into both today 00:04:41.000 --> 00:04:46.000 and on Monday. Important because polar molecules, 00:04:46.000 --> 00:04:50.000 such as water like this, are able to dissolve certain compounds. 00:04:50.000 --> 00:04:55.000 And nonpolar molecules, which have large arrays of these kinds of bonds 00:04:55.000 --> 00:05:00.000 or carbon-carbon bonds, these are relatively insoluble in 00:05:00.000 --> 00:05:04.000 water, and that has important consequences for the organization of 00:05:04.000 --> 00:05:08.000 biological membranes. We might have a carbonyl bond here, 00:05:08.000 --> 00:05:12.000 that is a C going to an O via a double bond. And here we have, 00:05:12.000 --> 00:05:15.000 once again, a situation where the oxygen is far more avid in terms of 00:05:15.000 --> 00:05:19.000 its willingness and interest in pulling electrons toward itself. 00:05:19.000 --> 00:05:22.000 And, therefore, the carbon gives up a little bit of the electron cloud 00:05:22.000 --> 00:05:26.000 and it becomes slightly electropositive. 00:05:26.000 --> 00:05:30.000 Whereas, the oxygen atom becomes slightly electronegative. 00:05:30.000 --> 00:05:35.000 Now, the fact of the matter is that there are also other bonds that are 00:05:35.000 --> 00:05:40.000 noncovalent and are much less energetic. For example, 00:05:40.000 --> 00:05:46.000 let's talk for a moment about a hydrogen bond. 00:05:46.000 --> 00:05:51.000 And it's perhaps easiest to demonstrate a hydrogen bond by 00:05:51.000 --> 00:05:57.000 looking at the structure of two neighboring water molecules in a 00:05:57.000 --> 00:06:02.000 solution of water of all things. And, the fact of the matter is, 00:06:02.000 --> 00:06:06.000 let's say we draw one water molecule down here and one water molecule 00:06:06.000 --> 00:06:11.000 down here. What will happen is that this oxygen atom over here by virtue 00:06:11.000 --> 00:06:15.000 of its electronegativity will have a certain affinity for pulling this 00:06:15.000 --> 00:06:20.000 hydrogen atom toward itself. And, in fact, what actually happens 00:06:20.000 --> 00:06:25.000 in real life, whatever that is at the molecular level, 00:06:25.000 --> 00:06:29.000 is that this hydrogen atom may actually be bouncing back and forth 00:06:29.000 --> 00:06:34.000 between these two oxygens. It may be rapidly an interchange 00:06:34.000 --> 00:06:38.000 between them. This interchange causes a strong association between 00:06:38.000 --> 00:06:43.000 two neighboring water molecules. And, indeed, represents the reason 00:06:43.000 --> 00:06:48.000 why water does not vaporize at room temperature because the water 00:06:48.000 --> 00:06:52.000 molecules have a strong affinity or an avidity for one another. 00:06:52.000 --> 00:06:57.000 And, therefore, just to take some illustrations out of the book, 00:06:57.000 --> 00:07:02.000 this is the way it's illustrated in the book. 00:07:02.000 --> 00:07:07.000 Probably good to have a screen down. And here you can see the way that 00:07:07.000 --> 00:07:12.000 water molecules are actually arrayed in water. This is the lower 00:07:12.000 --> 00:07:17.000 illustration here. Just to indicate to you that the 00:07:17.000 --> 00:07:22.000 hydrogen atoms are not really the possession, the ownership of one 00:07:22.000 --> 00:07:27.000 molecule of water. They're just constantly being 00:07:27.000 --> 00:07:32.000 exchanged back and forth. And this back and forth exchange, 00:07:32.000 --> 00:07:37.000 this sharing of a hydrogen atom is what enables a hydrogen bond of 00:07:37.000 --> 00:07:43.000 roughly 5 kilocalories of energy per mole to hold things together. 00:07:43.000 --> 00:07:46.000 5 kilocalories is not much. It's only one order of magnitude 00:07:46.000 --> 00:07:50.000 above 0.6 rather than being two orders of magnitude. 00:07:50.000 --> 00:07:53.000 And, therefore, if one raises the temperature to the level of boiling, 00:07:53.000 --> 00:07:57.000 if the temperature is high enough, the thermal energy is high enough to 00:07:57.000 --> 00:08:01.000 rip apart these kinds of associations. 00:08:01.000 --> 00:08:05.000 Now, if we were to go back here to look at this carbonyl atom we would 00:08:05.000 --> 00:08:10.000 find the following sort of situation. Here we have this unequal sharing 00:08:10.000 --> 00:08:15.000 of electropositive and electronegative bonds. 00:08:15.000 --> 00:08:20.000 Let's put an acidic group like this. This is a carboxylic acid right 00:08:20.000 --> 00:08:25.000 here. Here we see a carbon bond to a hydroxyl here via 00:08:25.000 --> 00:08:30.000 this oxygen atom. Here, once again, 00:08:30.000 --> 00:08:34.000 we have an electronegative atom. And, in fact, if we talk about an 00:08:34.000 --> 00:08:38.000 ionized acid, normally in the absence of ionization there would be 00:08:38.000 --> 00:08:42.000 a net zero charge right here. But at neutral pH it may well be 00:08:42.000 --> 00:08:47.000 the case that the association, for various reasons, between this 00:08:47.000 --> 00:08:51.000 oxygen and this hydrogen will allow the hydrogen, or rather the proton, 00:08:51.000 --> 00:08:55.000 the nucleus of the hydrogen atom to just wander away. 00:08:55.000 --> 00:08:59.000 And, therefore, we can imagine there could be a net negative 00:08:59.000 --> 00:09:04.000 charge here. A whole, this has one full electron, 00:09:04.000 --> 00:09:08.000 electronegative charge here, the charge of one electron, 00:09:08.000 --> 00:09:12.000 and this proton will have ionized, will have left the carboxylic group 00:09:12.000 --> 00:09:16.000 in which it originated, and now we have an ionized acid 00:09:16.000 --> 00:09:20.000 group. Either before or even after this ionization, 00:09:20.000 --> 00:09:24.000 there is a strong affinity of the carboxyl group with the water around 00:09:24.000 --> 00:09:28.000 it because let's look at what happened before the ionization 00:09:28.000 --> 00:09:33.000 occurred. This carbon here is strong and 00:09:33.000 --> 00:09:37.000 electronegative. And, therefore, it will participate 00:09:37.000 --> 00:09:42.000 in hydrogen bonding to the water solvent here, i. 00:09:42.000 --> 00:09:46.000 ., this proton will be shared a bit between the oxygen of the water 00:09:46.000 --> 00:09:51.000 molecule and the oxygen right here. Similarly, here this oxygen will be 00:09:51.000 --> 00:09:55.000 slightly electronegative for the reasons I've just described. 00:09:55.000 --> 00:10:00.000 And here, once again, there may be some weak hydrogen bonding going on. 00:10:00.000 --> 00:10:04.000 Although, not as effective as over here where we have a double-bond 00:10:04.000 --> 00:10:09.000 where we have a lot of concentration of a cloud of electrons pulled 00:10:09.000 --> 00:10:13.000 towards the oxygen atom. And this begins to give us clues as 00:10:13.000 --> 00:10:18.000 to why certain molecules are soluble in water and others are insoluble. 00:10:18.000 --> 00:10:22.000 For example, if we look at aliphatic compounds. 00:10:22.000 --> 00:10:27.000 Let's look at a compound that's structured like this. 00:10:27.000 --> 00:10:34.000 I guess most people would call this 00:10:34.000 --> 00:10:38.000 pentane. And we can call it that, too. And this has no 00:10:38.000 --> 00:10:42.000 electronegativity or positivity by virtue of the equal affinities of 00:10:42.000 --> 00:10:47.000 these two kinds of atoms, that is the hydrogen and the carbons 00:10:47.000 --> 00:10:51.000 for electrons. And as a consequence, 00:10:51.000 --> 00:10:55.000 this will not be able to form any hydrogen bonds with a solvent around 00:10:55.000 --> 00:11:00.000 it if the solvent happens to be water. 00:11:00.000 --> 00:11:05.000 So there's not good bonding here. And this will, in fact, also if one 00:11:05.000 --> 00:11:10.000 puts this in a solution of water, this will cause all the water 00:11:10.000 --> 00:11:15.000 molecules to line up in a certain way, almost a quasi-crystal around 00:11:15.000 --> 00:11:21.000 the aliphatic molecule. They'll be ordered in a certain 00:11:21.000 --> 00:11:26.000 layer around the aliphatic molecule without being able to form any 00:11:26.000 --> 00:11:31.000 strong hydrogen bonds with them. And this ordering represents a loss 00:11:31.000 --> 00:11:36.000 of chaos, a loss of entropy. Entropy is chaos. It's disorder. 00:11:36.000 --> 00:11:40.000 It's what happens, let's say, at 10:55 when we all leave the room, 00:11:40.000 --> 00:11:45.000 all of a sudden order becomes chaotic. And here, 00:11:45.000 --> 00:11:50.000 before this lining up occurred, the water molecules were chaotically 00:11:50.000 --> 00:11:55.000 arrayed throughout the solvent. After this lining up occurred there 00:11:55.000 --> 00:12:00.000 was a loss of entropy, there was a loss of chaos. 00:12:00.000 --> 00:12:03.000 And thermodynamics tells us that generally the ordering of molecules 00:12:03.000 --> 00:12:07.000 is disfavored. And consequently we now have two 00:12:07.000 --> 00:12:11.000 reasons why this molecule doesn't like to be in the midst of water. 00:12:11.000 --> 00:12:15.000 First of all, it's unable to form hydrogen bonds with the solvent. 00:12:15.000 --> 00:12:19.000 And second of all there is a decrease in the entropy, 00:12:19.000 --> 00:12:23.000 in the chaos that occurs when this molecule directly confronts water. 00:12:23.000 --> 00:12:27.000 And because of those two reasons it turns out that this molecule doesn't 00:12:27.000 --> 00:12:31.000 like to be in water. The aliphatic molecule, 00:12:31.000 --> 00:12:35.000 as one would call this in organic chemistry, doesn't like to be in 00:12:35.000 --> 00:12:40.000 water. And a dislike of water is often called its hydrophobicity, 00:12:40.000 --> 00:12:45.000 or we often call it hydro, might as well spell it right, 00:12:45.000 --> 00:12:49.000 hydrophobic, i.e., it really hates to be in water. 00:12:49.000 --> 00:12:54.000 In fact, class, there's a second meaning for 00:12:54.000 --> 00:12:59.000 hydrophobia, or hydrophobic has a second meaning. 00:12:59.000 --> 00:13:03.000 Every five years I ask a class to see who knows what the second 00:13:03.000 --> 00:13:07.000 meaning of hydrophobia is. This is really obscure. Sorry? 00:13:07.000 --> 00:13:12.000 Rabies, right. The TAs aren't allowed to answer that. 00:13:12.000 --> 00:13:16.000 If somebody has rabies, at one stage of rabies, almost near 00:13:16.000 --> 00:13:21.000 the terminal stage, the individual becomes hydrophobic 00:13:21.000 --> 00:13:25.000 because he or she doesn't like to drink water, for reasons that are 00:13:25.000 --> 00:13:30.000 obscure at least to me. Now, conversely, 00:13:30.000 --> 00:13:35.000 molecules that have carboxyl group on it would be called hydrophilic. 00:13:35.000 --> 00:13:40.000 And, as we'll see over this lecture and the next one, 00:13:40.000 --> 00:13:45.000 these hydrophobic and hydrophilic tendencies tend to have great 00:13:45.000 --> 00:13:50.000 affects on the overall behavior of molecules. Let's, 00:13:50.000 --> 00:13:55.000 for example, imagine a situation where we have a long aliphatic tail 00:13:55.000 --> 00:14:00.000 like this. In fact, these tails can go on in certain 00:14:00.000 --> 00:14:05.000 aliphatic compounds. They can go on for 20 or even 30 00:14:05.000 --> 00:14:09.000 carbons. And at the end of this, let's just put arbitrarily a 00:14:09.000 --> 00:14:13.000 carboxyl group. And let's say we ionized it. 00:14:13.000 --> 00:14:17.000 So here's an acidic group that's ionized. It's shed its proton. 00:14:17.000 --> 00:14:21.000 It's actually acquired a negative charge. And now we have something, 00:14:21.000 --> 00:14:25.000 this molecule is a bit schizoid. Because on one end of it, 00:14:25.000 --> 00:14:29.000 it loves to be in water, the other end of it hates to be in water. 00:14:29.000 --> 00:14:33.000 And this has strong affects. It's sometimes called amphipathic, 00:14:33.000 --> 00:14:37.000 but we don't need to worry about that word. And, 00:14:37.000 --> 00:14:42.000 therefore, this carboxyl head loves to stick its head, 00:14:42.000 --> 00:14:46.000 to immerse its head in water. And these things, the aliphatic 00:14:46.000 --> 00:14:51.000 portion hates to be in water. Now, as a consequence of these 00:14:51.000 --> 00:14:55.000 rather conflicted feelings that these molecules have about water, 00:14:55.000 --> 00:14:59.000 we can ask the question what happens when we put such molecules 00:14:59.000 --> 00:15:04.000 actually into water? And what we see here is the 00:15:04.000 --> 00:15:09.000 following. That if we were to construct, for example, 00:15:09.000 --> 00:15:13.000 a molecule of the sort that has here, in this case we're talking about a 00:15:13.000 --> 00:15:18.000 molecule that has two hydrophobic tails. We'll get into its detailed 00:15:18.000 --> 00:15:23.000 structure shortly, but just imagine for a moment two 00:15:23.000 --> 00:15:28.000 long hydrophobic tails out here ended with a hydrophilic head. 00:15:28.000 --> 00:15:33.000 And under such situations, if we put thousands of these or 00:15:33.000 --> 00:15:38.000 millions of these molecules into a solution of water, 00:15:38.000 --> 00:15:43.000 what we will then see is, no pointer? All right. Pointer? 00:15:43.000 --> 00:15:48.000 All right. What we will then see is that the hydrophilic head groups, 00:15:48.000 --> 00:15:53.000 which are here depicted in red, will point their way outwards, 00:15:53.000 --> 00:15:59.000 they will want to stick their heads in water. 00:15:59.000 --> 00:16:03.000 And conversely the hydrophobic tails fleeing from the water will actually 00:16:03.000 --> 00:16:08.000 associate one with the other. And so you have a structure that's 00:16:08.000 --> 00:16:12.000 called, in this case, an a micelle where you form this 00:16:12.000 --> 00:16:17.000 little globular sphere where the lipid tails are tucked inside. 00:16:17.000 --> 00:16:22.000 And, therefore, are actually being shielded from any direct exposure to 00:16:22.000 --> 00:16:26.000 water. This structure down here, the lipid bilayer, is actually, as 00:16:26.000 --> 00:16:31.000 we will discuss in greater detail shortly, the overall topology of the 00:16:31.000 --> 00:16:36.000 way most biological membranes are organized. 00:16:36.000 --> 00:16:40.000 In fact, virtually all of them. Why is that? Because biological 00:16:40.000 --> 00:16:45.000 membranes separate two hydrophilic or two aqueous spaces. 00:16:45.000 --> 00:16:50.000 Thank you, sir. A gentleman you are. So here is an aqueous space 00:16:50.000 --> 00:16:55.000 and here is an aqueous space. And as we see the hydrophilic heads 00:16:55.000 --> 00:17:00.000 are immersed or sticking their heads into the hydrophilic space. 00:17:00.000 --> 00:17:04.000 This is called a lipid bilayer. And, obviously, it's highly 00:17:04.000 --> 00:17:08.000 effective for separately these two aqueous compartments. 00:17:08.000 --> 00:17:12.000 In eukaryotic cells, as I mentioned last time, there is an enormous 00:17:12.000 --> 00:17:16.000 premium placed on separating and segregating different aqueous 00:17:16.000 --> 00:17:20.000 compartments which is invariably achieved through the device of 00:17:20.000 --> 00:17:24.000 constructing these lipid bilayers. Here's a vesicle. A vesicle is 00:17:24.000 --> 00:17:28.000 more complicated than a micelle. Because if you look at the membrane 00:17:28.000 --> 00:17:32.000 lining the vesicle, you see it's actually a lipid 00:17:32.000 --> 00:17:36.000 bilayer, but one that in 3-dimensional space is actually a 00:17:36.000 --> 00:17:40.000 sphere. And in the case of this vesicle, we can well imagine that on 00:17:40.000 --> 00:17:43.000 the inside of the vesicle water is kept, can be stored, 00:17:43.000 --> 00:17:47.000 and on the outside of the vesicle water can be stored. 00:17:47.000 --> 00:17:51.000 And many of the membranes that we see within the cytoplasms themselves 00:17:51.000 --> 00:17:55.000 are actually constructed on this kind of design. 00:17:55.000 --> 00:17:58.000 So when we draw, for example, in this case the Golgi 00:17:58.000 --> 00:18:02.000 apparatus, which I mentioned to you in passing last time we met, 00:18:02.000 --> 00:18:05.000 each one of these membranes here, it's obviously drawn as a double 00:18:05.000 --> 00:18:09.000 line, but whenever you see a membrane indicated, 00:18:09.000 --> 00:18:13.000 implicit in that drawing is the fact that each one of these membranes is 00:18:13.000 --> 00:18:16.000 actually a bilayer. There are never any monolayers of 00:18:16.000 --> 00:18:20.000 lipids in living cells. Each one of these vesicles you see 00:18:20.000 --> 00:18:24.000 here is actually a lipid bilayer with an aqueous inside and, 00:18:24.000 --> 00:18:28.000 once again, aqueous on the outside. Again, much of the thermodynamic 00:18:28.000 --> 00:18:34.000 stability that allows these vesicles to remain intact rather than just 00:18:34.000 --> 00:18:39.000 diffuse apart is created by these hydrophilic and hydrophobic forces 00:18:39.000 --> 00:18:45.000 which tie such molecules together or will rip them apart. 00:18:45.000 --> 00:18:51.000 Now, in truth there are yet other kinds of forces that govern the 00:18:51.000 --> 00:18:56.000 affinity of molecules to one another. For example, let's imagine a 00:18:56.000 --> 00:19:02.000 situation where we have an ionized acid group of the sort we just 00:19:02.000 --> 00:19:07.000 talked about before. Now, by the way, 00:19:07.000 --> 00:19:11.000 here, let's say I'll draw the negative charge on one of these two 00:19:11.000 --> 00:19:15.000 oxygens, if you can see that. But the truth is that the electrons 00:19:15.000 --> 00:19:19.000 are swarming back and forth, and so the negative charge is shared 00:19:19.000 --> 00:19:23.000 equally, the negative one electron charge is shared equally between 00:19:23.000 --> 00:19:27.000 these two oxygen atoms. And this is obviously an area of 00:19:27.000 --> 00:19:32.000 great electronegativity. Independent of that, 00:19:32.000 --> 00:19:36.000 let's imagine up here we have a basic group, let's say an amine 00:19:36.000 --> 00:19:40.000 group over here. And, the fact of the matter is, 00:19:40.000 --> 00:19:44.000 amine groups, NH2 groups, that's what an amine is, 00:19:44.000 --> 00:19:48.000 here's an amine group. This is a carboxylic group. 00:19:48.000 --> 00:19:52.000 And the amine group, which is used very often in biochemistry, 00:19:52.000 --> 00:19:56.000 actually has an affinity. It has an unpaired set of electrons on the 00:19:56.000 --> 00:20:00.000 nitrogen, and so it likes to attract protons to it, 00:20:00.000 --> 00:20:04.000 which makes it, causes it to be called basic. 00:20:04.000 --> 00:20:08.000 And this attraction, the scavenging of protons, 00:20:08.000 --> 00:20:12.000 perhaps from the water, will obviously give this whole group here 00:20:12.000 --> 00:20:16.000 a net positive charge, a charge equal to the charge of one 00:20:16.000 --> 00:20:20.000 proton. Here, once again, we can imagine this is 00:20:20.000 --> 00:20:24.000 hydrophilic because this charge group can once again also associate 00:20:24.000 --> 00:20:29.000 quite intimately with aqueous solvent. 00:20:29.000 --> 00:20:33.000 Now, independent of any other forces that might exist here, 00:20:33.000 --> 00:20:37.000 indeed one could imagine situations where there is a sharing of a proton. 00:20:37.000 --> 00:20:41.000 And, therefore, a hydrogen bond formed between these 00:20:41.000 --> 00:20:45.000 two. Independent of that is the simple electrostatic interaction of 00:20:45.000 --> 00:20:50.000 these two groups. That is the mutual attraction of 00:20:50.000 --> 00:20:54.000 positive and negative groups, one to the other. And the 00:20:54.000 --> 00:20:58.000 electrostatic interactions, you cannot quantify exactly how many 00:20:58.000 --> 00:21:02.000 kilocalories a mole there is because the energetic value in electrostatic 00:21:02.000 --> 00:21:06.000 interaction is equal to one over r squared where r is the distance 00:21:06.000 --> 00:21:11.000 between these two charged groups. And obviously the further apart you 00:21:11.000 --> 00:21:15.000 get the weaker the attraction with one another. There are also what 00:21:15.000 --> 00:21:19.000 are called van der Walls interactions. There are largely of 00:21:19.000 --> 00:21:23.000 interest to a very small community of biochemists. 00:21:23.000 --> 00:21:27.000 You probably will never, you may never hear this term again 00:21:27.000 --> 00:21:32.000 in your life. And van der Waals interactions come 00:21:32.000 --> 00:21:36.000 from the fact that if we were to have, for example, 00:21:36.000 --> 00:21:40.000 two molecules over here which are not normally charged in any way, 00:21:40.000 --> 00:21:44.000 let's just talk about two aliphatic chains again. And I won't put in 00:21:44.000 --> 00:21:49.000 all the protons and everything, but just imagine a situation like 00:21:49.000 --> 00:21:53.000 this. What will happen is that because of the fluctuations of 00:21:53.000 --> 00:21:57.000 electrons, because the electrons are swimming around here all the time, 00:21:57.000 --> 00:22:02.000 moving from one area to the next they're never equally distributed 00:22:02.000 --> 00:22:06.000 homogenously over a long period of time, there will be brief instance 00:22:06.000 --> 00:22:10.000 in time, microseconds or even nanoseconds when there happens to be 00:22:10.000 --> 00:22:15.000 more electrons over here than right here. 00:22:15.000 --> 00:22:19.000 Just by chance. And this area of unequal 00:22:19.000 --> 00:22:23.000 distribution of electrons will in turn induce the opposite kind of 00:22:23.000 --> 00:22:27.000 electron shift in a neighboring molecule down here. 00:22:27.000 --> 00:22:31.000 Obviously, depending on the distance between them. 00:22:31.000 --> 00:22:34.000 But the negative here will repel electrons down here. 00:22:34.000 --> 00:22:38.000 The positive here will attract electrons down here. 00:22:38.000 --> 00:22:42.000 And so you will have these two quasi-polar arrangements here and 00:22:42.000 --> 00:22:46.000 here, very ephemeral, that is lasting for a very short 00:22:46.000 --> 00:22:50.000 transient period of time. But, nonetheless, sufficient to 00:22:50.000 --> 00:22:54.000 give a very weak interaction between these two molecules which may 00:22:54.000 --> 00:22:58.000 persist only for a microsecond and then be dissipated because the 00:22:58.000 --> 00:23:02.000 charges then redistributed once again. 00:23:02.000 --> 00:23:06.000 And, as a consequence of that, one has very weak interactions which, 00:23:06.000 --> 00:23:11.000 in the great scheme of things, play only a very minor role in the 00:23:11.000 --> 00:23:16.000 overall energy which holds molecules together. Now, 00:23:16.000 --> 00:23:21.000 with that background in mind, let's begin to elaborate on it, 00:23:21.000 --> 00:23:25.000 on how we can make molecules that have interesting properties that 00:23:25.000 --> 00:23:30.000 enable them, among other things, to participate in the construction 00:23:30.000 --> 00:23:35.000 of lipid bilayers, which will be the first object of 00:23:35.000 --> 00:23:40.000 our attentions today in terms of actual biochemistry. 00:23:40.000 --> 00:23:44.000 So here's a fatty acid. We see that up here. I, 00:23:44.000 --> 00:23:48.000 in effect, drew you the structure of a fatty acid up here already once 00:23:48.000 --> 00:23:53.000 before. And what we can see is through a linkage known as 00:23:53.000 --> 00:23:57.000 esterification we can create this molecule. So what do I 00:23:57.000 --> 00:24:02.000 mean by esterification? Well, in this case we're talking 00:24:02.000 --> 00:24:07.000 about a situation here where we have a carbon atom over here like this 00:24:07.000 --> 00:24:12.000 with a hydroxyl group. You see it over here. And what 00:24:12.000 --> 00:24:17.000 we're doing is we're dehydrating this, we're pulling out one net 00:24:17.000 --> 00:24:22.000 molecule of water. And each time we do that, 00:24:22.000 --> 00:24:27.000 on three separate occasions, what we end up doing is to create 00:24:27.000 --> 00:24:32.000 instead of this is to create a covalent bond between these two. 00:24:32.000 --> 00:24:36.000 And so the end product of dehydrating this, 00:24:36.000 --> 00:24:40.000 pulling out one net molecule of water is that we end up with a 00:24:40.000 --> 00:24:48.000 structure that looks like this. 00:24:48.000 --> 00:24:53.000 And you see that happening on at least three different occasions, 00:24:53.000 --> 00:24:58.000 here, here and here. Well, actually, I should put a carbon over here. 00:24:58.000 --> 00:25:02.000 So here we have three esterifications. 00:25:02.000 --> 00:25:07.000 The hydroxyl group in each case is reacting with a carboxyl group here 00:25:07.000 --> 00:25:11.000 pulling out one water, and each case creating what's called 00:25:11.000 --> 00:25:16.000 triacylglyercol or triglyceride. Triglyceride refers to the fact 00:25:16.000 --> 00:25:21.000 that we started here with a glycerol and we have now esterified it. 00:25:21.000 --> 00:25:25.000 Now, in fact, there are two directions here in this 00:25:25.000 --> 00:25:30.000 kind of reaction. Esterification is the kind of 00:25:30.000 --> 00:25:34.000 linkage that we just showed here. And the truth is that vast numbers 00:25:34.000 --> 00:25:38.000 of biochemical linkages are made by esterification reactions and 00:25:38.000 --> 00:25:43.000 reversed by reactions that are called simply hydrolysis. 00:25:43.000 --> 00:25:47.000 And, in this case, what we're referring to is the fact that if one 00:25:47.000 --> 00:25:51.000 were to reintroduce a water molecule into each of these three linkages, 00:25:51.000 --> 00:25:56.000 one, two and three, we would break the bond and cause this entire 00:25:56.000 --> 00:26:00.000 structure to revert to the two precursors that existed or 00:26:00.000 --> 00:26:05.000 preexisted prior to these three esterification reactions. 00:26:05.000 --> 00:26:10.000 And time and again you'll see, over the next weeks, that 00:26:10.000 --> 00:26:16.000 esterification reactions are important for constructing different 00:26:16.000 --> 00:26:22.000 kinds of molecules. Now, the fact of the matter is we 00:26:22.000 --> 00:26:28.000 can do other kinds of modifications of a glycerol like this. 00:26:28.000 --> 00:26:32.000 Here what we've done, instead of adding a third fatty acid, 00:26:32.000 --> 00:26:36.000 note what was done here. Here through an esterification, 00:26:36.000 --> 00:26:40.000 let's look up at this one here, instead of adding a third fatty acid, 00:26:40.000 --> 00:26:44.000 we've saved, we've reserved one of the three groups of the glycerol. 00:26:44.000 --> 00:26:48.000 Here's what we saw just before. We've saved one of the three groups 00:26:48.000 --> 00:26:52.000 of the glycerol and put on instead this highly hydrophilic phosphate 00:26:52.000 --> 00:26:56.000 group, once again through a dehydration reaction, an 00:26:56.000 --> 00:27:00.000 esterification reaction. And now what we've done is add 00:27:00.000 --> 00:27:04.000 insult to injury because in the absence of this phosphate it would 00:27:04.000 --> 00:27:07.000 have a hydroxyl here which is mildly hydrophilic. But now look how 00:27:07.000 --> 00:27:11.000 strongly charged this is. Here are two negative charges, 00:27:11.000 --> 00:27:14.000 one electron each. And this is already a bit electronegative. 00:27:14.000 --> 00:27:18.000 So here we have an extremely potent hydrophilic entity. 00:27:18.000 --> 00:27:21.000 And here the degree of schizophrenia between one end of the 00:27:21.000 --> 00:27:25.000 molecule and the other is greatly exaggerated. Here, 00:27:25.000 --> 00:27:29.000 in fact, this is extremely hydrophilic. 00:27:29.000 --> 00:27:33.000 And, as a consequence of that, this really likes to stick its head 00:27:33.000 --> 00:27:37.000 inside water. And when we therefore talk about, we draw the images of 00:27:37.000 --> 00:27:41.000 different kinds of membranes, like this I showed you before the 00:27:41.000 --> 00:27:46.000 two tails. Here you saw the two tails I drew before in that diagram. 00:27:46.000 --> 00:27:50.000 Here's what we can imagine they actually look like in more real 00:27:50.000 --> 00:27:54.000 molecular terms. And the hydrophilic heads sticking 00:27:54.000 --> 00:27:58.000 in the water, this is just repeating what we saw before, 00:27:58.000 --> 00:28:03.000 become even more hydrophilic if we look at a molecule like this. 00:28:03.000 --> 00:28:07.000 Let's look at this thing here. Here's a very long hydrophobic tail. 00:28:07.000 --> 00:28:11.000 Here are the two glycerols once again. Here is the phosphate. 00:28:11.000 --> 00:28:15.000 And keep in mind that phosphate obviously has these extra oxygens. 00:28:15.000 --> 00:28:19.000 Phosphate can react with more than just one partner, 00:28:19.000 --> 00:28:23.000 the glycerol down here. In this case we've added this group 00:28:23.000 --> 00:28:27.000 up here. And this group up here is, once again, this happens to be a 00:28:27.000 --> 00:28:31.000 serine which is an amino acid, this also happens to be quite 00:28:31.000 --> 00:28:35.000 hydrophilic. Here's our old friend the basic 00:28:35.000 --> 00:28:39.000 amino group. Here's the carboxyl group. This is a bit hydrophobic, 00:28:39.000 --> 00:28:43.000 CH2. And then we once again have the hydrophilic head here. 00:28:43.000 --> 00:28:47.000 And, therefore, we imagine, if we look at what's called a 00:28:47.000 --> 00:28:50.000 space-filling model, and a space-filling model really is 00:28:50.000 --> 00:28:54.000 intended to show us what one imagines if one had this vision, 00:28:54.000 --> 00:28:58.000 which we don't have, how much space each of these atoms would actually 00:28:58.000 --> 00:29:02.000 take up if one were able to see them. 00:29:02.000 --> 00:29:07.000 And here we see this space filling model. This lipid molecule here is 00:29:07.000 --> 00:29:12.000 actually slightly kinked with its hydrophilic head tucked into the 00:29:12.000 --> 00:29:18.000 water space. And so here's actually the way that many biological 00:29:18.000 --> 00:29:23.000 membranes look in terms of the way that they are constructed. 00:29:23.000 --> 00:29:28.000 Now, the fact of the matter is this also affords the cell the ability to 00:29:28.000 --> 00:29:34.000 segregate contents on one or the other side of whatever lipid bilayer 00:29:34.000 --> 00:29:39.000 it happens to have constructed. And here we can see about the 00:29:39.000 --> 00:29:44.000 semi-permeability, how permeable these membranes are to 00:29:44.000 --> 00:29:49.000 different kinds of molecules. Permeability obviously refers to 00:29:49.000 --> 00:29:54.000 the ability of this membrane to obstruct or to allow the migration 00:29:54.000 --> 00:30:00.000 of molecules from one side to the other. 00:30:00.000 --> 00:30:03.000 Ions, and these ions we see right here are obviously highly 00:30:03.000 --> 00:30:07.000 hydrophilic by virtue of their charge. That's explains, 00:30:07.000 --> 00:30:11.000 in fact, why, for example, table salt goes so readily into 00:30:11.000 --> 00:30:15.000 solution, because it readily ionizes into sodium, NA and CL, 00:30:15.000 --> 00:30:18.000 which then are avidly taken up by the water molecules. 00:30:18.000 --> 00:30:22.000 So these are highly hydrophilic ions. And the questions is, 00:30:22.000 --> 00:30:26.000 can they go from one side of the membrane to the other? 00:30:26.000 --> 00:30:30.000 And the answer is absolutely not or highly improbably. Why? 00:30:30.000 --> 00:30:33.000 Because these are so highly hydrophilic, the water molecules 00:30:33.000 --> 00:30:37.000 love to gather around them and form hydrogen bonds and electrostatic 00:30:37.000 --> 00:30:40.000 bonds with them. And if one of these ions ventures 00:30:40.000 --> 00:30:44.000 over here, it's going from an area where it's warmly embraced by the 00:30:44.000 --> 00:30:47.000 solvent molecules to an area where these molecules intensely dislike 00:30:47.000 --> 00:30:51.000 these ions. And, therefore, thermodynamically the 00:30:51.000 --> 00:30:55.000 entrance of any one of these ions into the membrane, 00:30:55.000 --> 00:30:58.000 into the hydrophobic portion of the membrane is highly disfavored, 00:30:58.000 --> 00:31:02.000 which makes the membrane essentially, for all practical purposes, 00:31:02.000 --> 00:31:05.000 impermeable. The same can be said of glucose 00:31:05.000 --> 00:31:09.000 which happens to be a carbohydrate. We'll talk about it shortly. But 00:31:09.000 --> 00:31:12.000 it's also nicely hydrophilic. It also can go in water. In fact, 00:31:12.000 --> 00:31:15.000 it can go through. And it's actually the case, 00:31:15.000 --> 00:31:19.000 to my knowledge, that one doesn't really understand to this day why 00:31:19.000 --> 00:31:22.000 lipid bilayers are reasonably permeable to water. 00:31:22.000 --> 00:31:26.000 You would say, well, water shouldn't be able to go 00:31:26.000 --> 00:31:29.000 through. It clearly doesn't have to have a 00:31:29.000 --> 00:31:32.000 net positive or negative charge, but the physical chemist, if you 00:31:32.000 --> 00:31:35.000 asked them why does water, why is water able to go through 00:31:35.000 --> 00:31:38.000 lipid bilayers? They'll say, well, 00:31:38.000 --> 00:31:41.000 we've been working on that and we'll get you an answer in the next five 00:31:41.000 --> 00:31:44.000 or ten years. And they said that 40 years ago and 30 years ago, 00:31:44.000 --> 00:31:47.000 and they're still saying it. And we don't really understand why 00:31:47.000 --> 00:31:50.000 water goes through, which is an embarrassment because 00:31:50.000 --> 00:31:53.000 here's one of the fundamental biochemical properties of living 00:31:53.000 --> 00:31:56.000 matter that is poorly understood. Gases can go right through. 00:31:56.000 --> 00:32:00.000 And amino acids, ATP, glucose 6 phosphate, 00:32:00.000 --> 00:32:05.000 highly hydrophilic, can also not go through. Now, 00:32:05.000 --> 00:32:09.000 the advantage of this is that a cell can accumulate large concentrations 00:32:09.000 --> 00:32:14.000 of these molecules either on the inside or it can pump them to the 00:32:14.000 --> 00:32:19.000 outside. In other words, it can create great gradients in the 00:32:19.000 --> 00:32:23.000 concentrations of different kinds of ions. For example, 00:32:23.000 --> 00:32:28.000 in many cells, the concentration of calcium, CA++ is a thousand times 00:32:28.000 --> 00:32:33.000 higher on the outside of the cell than on the inside of the cell which 00:32:33.000 --> 00:32:38.000 is a testimonial to how impermeable these lipid bilayer membranes are. 00:32:38.000 --> 00:32:41.000 The fact of the matter is I'm fudging a little bit here because in 00:32:41.000 --> 00:32:45.000 the lipid bilayers of the plasma membrane of the cell, 00:32:45.000 --> 00:32:49.000 the outer membrane of the cell that we talked about in passing last time, 00:32:49.000 --> 00:32:53.000 there are ion pumps which are constantly working away pumping ions 00:32:53.000 --> 00:32:57.000 from one side to the other overcomes the little bit of leakage which may 00:32:57.000 --> 00:33:01.000 have occurred if a calcium ion happens to have snuck through in one 00:33:01.000 --> 00:33:05.000 direction or the other. And we end up expending a lot of 00:33:05.000 --> 00:33:10.000 energy to keep these ion gradients in appropriate concentrations on the 00:33:10.000 --> 00:33:15.000 outside and the inside. In fact, virtually all the energy 00:33:15.000 --> 00:33:20.000 that is expended in our brain, almost all of it is expended to 00:33:20.000 --> 00:33:25.000 power the ion pumps which are constantly insuring that the 00:33:25.000 --> 00:33:30.000 concentrations of certain ions on the outside and the inside of 00:33:30.000 --> 00:33:36.000 neurons are kept at their proper respective levels. 00:33:36.000 --> 00:33:40.000 It could therefore be that actually more than half of our metabolic 00:33:40.000 --> 00:33:44.000 burden every day is expended just keeping the ions segregated on the 00:33:44.000 --> 00:33:48.000 outside and inside of cells. For example, potassium is at high 00:33:48.000 --> 00:33:52.000 levels inside cells, sodium is at high levels outside 00:33:52.000 --> 00:33:56.000 cells, just to site some arbitrary examples. There are also, 00:33:56.000 --> 00:34:00.000 by the way, as I mentioned last time, channels. 00:34:00.000 --> 00:34:04.000 And channels are actually just little doughnut shaped objects which 00:34:04.000 --> 00:34:08.000 are placed, inserted into lipid bilayers in the plasma membranes and 00:34:08.000 --> 00:34:13.000 just allow for the passive diffusion of an ion through them, 00:34:13.000 --> 00:34:17.000 through the doughnut hole enabling an ion, so if here's the lipid 00:34:17.000 --> 00:34:22.000 bilayer, not showing its two things, these kinds of doughnut shaped 00:34:22.000 --> 00:34:26.000 protein aggregates will allow the passage of ions in one 00:34:26.000 --> 00:34:31.000 direction or another. And here energy is not being 00:34:31.000 --> 00:34:35.000 expended to enable this passage. It may just be through diffusion. 00:34:35.000 --> 00:34:39.000 If there's a higher concentration of ion on side of the lipid bilayer 00:34:39.000 --> 00:34:43.000 and a lower one on this side, this diffusion will allow the ion to 00:34:43.000 --> 00:34:47.000 migrate through the bore of the ion channel from one side to the other. 00:34:47.000 --> 00:34:51.000 In fact, even though this does not involve the expenditure of energy on 00:34:51.000 --> 00:34:55.000 the part of the cell, the cell may actually use a gating 00:34:55.000 --> 00:35:00.000 mechanism to open or close these channels. 00:35:00.000 --> 00:35:04.000 When the channels are closed then the ions cannot move through. 00:35:04.000 --> 00:35:08.000 When the channels are gated open then diffusion can take over and 00:35:08.000 --> 00:35:12.000 insure the transfer, the transportation of ions from one 00:35:12.000 --> 00:35:17.000 side to the other. Now, having said that, 00:35:17.000 --> 00:35:21.000 we can begin to look at yet other higher level structures. 00:35:21.000 --> 00:35:25.000 Here, by the way, is a better drawing than the one I provided you. 00:35:25.000 --> 00:35:30.000 This comes from your book of what a vesicle looks like. 00:35:30.000 --> 00:35:34.000 Here's what it looks like under the electron microscope and here's what 00:35:34.000 --> 00:35:39.000 it looks like when a talented rather than hapless and hopeless artist 00:35:39.000 --> 00:35:44.000 like myself tries to draw it. So let's just say that's our intro 00:35:44.000 --> 00:35:49.000 into lipids and membranes. And let's move onto the next layer 00:35:49.000 --> 00:35:54.000 of complexity. And the next layer of complexity in 00:35:54.000 --> 00:35:59.000 terms of molecules represents carbohydrates. 00:35:59.000 --> 00:36:03.000 And when we talk about a carbohydrate amongst ourselves we're 00:36:03.000 --> 00:36:07.000 talking about a molecule which, roughly speaking, has one carbon 00:36:07.000 --> 00:36:11.000 atom for every water molecule. And we'll shortly indulge ourselves 00:36:11.000 --> 00:36:15.000 in talking about all kinds of different carbohydrate molecules. 00:36:15.000 --> 00:36:19.000 Here is really one of the most important carbohydrate molecules, 00:36:19.000 --> 00:36:23.000 glucose. And what should we note about glucose? 00:36:23.000 --> 00:36:27.000 Well, the first thing you should see is that glucose has six carbon 00:36:27.000 --> 00:36:31.000 atoms. And, therefore, as a consequence it's called a 00:36:31.000 --> 00:36:35.000 hexose. We're going to talk about pentoses 00:36:35.000 --> 00:36:39.000 very shortly. They only have five, to state the obvious. Glycerol, 00:36:39.000 --> 00:36:44.000 which we talked about before, is also considered in one sense a 00:36:44.000 --> 00:36:48.000 carbohydrate, but it's been called by some people a triose. 00:36:48.000 --> 00:36:53.000 It only has three carbon atoms. And you can imagine, therefore, in 00:36:53.000 --> 00:36:57.000 principal that there are certain biochemical mechanisms which indeed 00:36:57.000 --> 00:37:02.000 exist which enable one to join two glycerol molecules, 00:37:02.000 --> 00:37:07.000 one to the other, to create something like a hexose, glucose. 00:37:07.000 --> 00:37:11.000 In fact, what we see from this drawing, expertly drawn by yours 00:37:11.000 --> 00:37:16.000 truly, is that the hexose molecule isn't really a linear molecule in 00:37:16.000 --> 00:37:20.000 solution. What happens is that because of various steric and 00:37:20.000 --> 00:37:25.000 thermodynamic forces it likes to cyclize. So let me just mention, 00:37:25.000 --> 00:37:30.000 I've just used two words that are useful to know about. 00:37:30.000 --> 00:37:34.000 Steric or stereochemistry refers to the 3-dimensional structure of a 00:37:34.000 --> 00:37:39.000 molecule. And, obviously, the stereochemistry of a 00:37:39.000 --> 00:37:43.000 molecule is dictated by the flexibility with which participating 00:37:43.000 --> 00:37:48.000 atoms can form bonds, whether we have a trivalent atom 00:37:48.000 --> 00:37:52.000 like nitrogen or a tetravalent atom like carbon or a monovalent 00:37:52.000 --> 00:37:57.000 like hydrogen. And these structures, 00:37:57.000 --> 00:38:03.000 the stereochemistry is dictated both by what atoms are present here and 00:38:03.000 --> 00:38:08.000 by thermodynamic considerations which cause this particular hexose, 00:38:08.000 --> 00:38:13.000 indeed virtually all hexoses, to cyclize. When I say cyclize, 00:38:13.000 --> 00:38:19.000 obviously I mean to form a circular structure. Here we note one thing. 00:38:19.000 --> 00:38:24.000 You can see how the hydroxyl here actually attacks the positively 00:38:24.000 --> 00:38:30.000 charged carbon here in order to form this cyclic structure. 00:38:30.000 --> 00:38:36.000 You see one of the six points on this hexagonal structure here is 00:38:36.000 --> 00:38:43.000 oxygen. It's not carbon at all. So there is one oxygen and five 00:38:43.000 --> 00:38:49.000 carbons. And one of the carbons is relegated, is exiled to outside of 00:38:49.000 --> 00:38:56.000 the circle. It's sometimes called an extracyclic because it's sticking 00:38:56.000 --> 00:39:02.000 out from the actual circle. And this is the structure in which 00:39:02.000 --> 00:39:06.000 glucose actually exists inside cells. And, in fact, 00:39:06.000 --> 00:39:10.000 there is, in truth, two alternative ways by which 00:39:10.000 --> 00:39:14.000 glucose can cyclize, whether the oxygen attacks the 00:39:14.000 --> 00:39:18.000 carbon on the carbonyl group underneath or on top. 00:39:18.000 --> 00:39:22.000 And you see that gives us two alternative structures. 00:39:22.000 --> 00:39:26.000 What's different about them? Well, if we think about this hexose 00:39:26.000 --> 00:39:30.000 as existing in a plane, or the hexagon is in a plane 00:39:30.000 --> 00:39:35.000 In this case the oxygen is above the plane and the hydrogen is below the 00:39:35.000 --> 00:39:40.000 plane. With equal probability you can have these two atoms reversed 00:39:40.000 --> 00:39:45.000 where hydrogen is now above the plane and hydroxyl is below the 00:39:45.000 --> 00:39:50.000 plane. And both of these structures, these alternative structures can 00:39:50.000 --> 00:39:55.000 fairly be considered to be glucose. Now, let's get a little bit more 00:39:55.000 --> 00:40:00.000 complicated. Here we have fructose and we have galactose. 00:40:00.000 --> 00:40:04.000 And what we see here is, by the way, that we have exactly the 00:40:04.000 --> 00:40:08.000 same number of carbon atoms and hydrogen atoms and oxygen atoms but 00:40:08.000 --> 00:40:12.000 they're hooked up slightly differently. And here now we begin 00:40:12.000 --> 00:40:16.000 to get very picky about the disposition, the orientation of 00:40:16.000 --> 00:40:20.000 these different kinds of hydroxyls and hydrogens. 00:40:20.000 --> 00:40:24.000 And note, by the way, here that in many cases one doesn't 00:40:24.000 --> 00:40:28.000 even put in the H for the hydrogen. It's just implied by the end of 00:40:28.000 --> 00:40:31.000 this line. And here, if you were to look at 00:40:31.000 --> 00:40:35.000 this, you'll see here now we have two extra cyclic carbons. 00:40:35.000 --> 00:40:38.000 Here's galactose which is yet another hexose. 00:40:38.000 --> 00:40:41.000 These are all hexoses, but their stereochemistry creates 00:40:41.000 --> 00:40:45.000 quite different kinds of structures. And it turns out that this 00:40:45.000 --> 00:40:48.000 stereochemistry is extremely important. These molecules function 00:40:48.000 --> 00:40:52.000 very differently, one from the other. 00:40:52.000 --> 00:40:55.000 And, for example, to the extent that glucose is used 00:40:55.000 --> 00:40:59.000 in different kinds of energy metabolism and to the extent that 00:40:59.000 --> 00:41:03.000 galactose is not, there must be certain biochemical 00:41:03.000 --> 00:41:07.000 mechanisms in which one has catalysts, the catalysts that we 00:41:07.000 --> 00:41:11.000 call enzymes that ensure that one can convert one of these hexoses 00:41:11.000 --> 00:41:14.000 through an enzyme into, let's say a less useful one into a 00:41:14.000 --> 00:41:18.000 more useful one, glucose, which can readily be burnt 00:41:18.000 --> 00:41:22.000 up by the energy-generating machinery. Here we've gone yet 00:41:22.000 --> 00:41:26.000 another order of magnitude more complex because we've gone from a 00:41:26.000 --> 00:41:30.000 monosaccharide, i.e., one or another hexose, 00:41:30.000 --> 00:41:34.000 to a disaccharide. And here's common table sugar. 00:41:34.000 --> 00:41:38.000 And here you see that it's formed once again through an esterification 00:41:38.000 --> 00:41:42.000 reaction, i.e. there is a dehydration reaction 00:41:42.000 --> 00:41:46.000 between this hydroxyl here and this hydroxyl here. 00:41:46.000 --> 00:41:50.000 And biochemists take the orientation of these hydroxyl and 00:41:50.000 --> 00:41:54.000 hydrogen groups very seriously. Now, you can say they're a bit 00:41:54.000 --> 00:41:58.000 obsessive. Indeed they probably are. 00:41:58.000 --> 00:42:02.000 But, nonetheless, we can admit that the specific 00:42:02.000 --> 00:42:07.000 orientations of all these things dictate very importantly the 00:42:07.000 --> 00:42:11.000 difference between here, in this case sucrose, and in this 00:42:11.000 --> 00:42:16.000 case lactose. Why is this important? Well, this is the sugar in milk 00:42:16.000 --> 00:42:20.000 sugar. This is the dominant sugar in milk sugar, 00:42:20.000 --> 00:42:25.000 lactose. And half the world, as adults, cannot absorb this. 00:42:25.000 --> 00:42:29.000 All kinds of unpleasant things happen when they actually 00:42:29.000 --> 00:42:34.000 drink milk. How many people here are lactose 00:42:34.000 --> 00:42:38.000 intolerant? It's nothing to be ashamed of. I'm married to a very 00:42:38.000 --> 00:42:43.000 lactose intolerant person. She's otherwise very nice. 00:42:43.000 --> 00:42:48.000 The fact is that the enzyme to break down lactose, 00:42:48.000 --> 00:42:52.000 it's an enzyme which is called lactase. And here we have yet 00:42:52.000 --> 00:42:57.000 another nomenclature item. So lactase is the enzyme which 00:42:57.000 --> 00:43:02.000 breaks down lactose. And, by the way, 00:43:02.000 --> 00:43:06.000 this is just the harbinger of many other enzymes we're going to talk 00:43:06.000 --> 00:43:10.000 about in the future that end in A-S-E. Whereas, 00:43:10.000 --> 00:43:14.000 carbohydrates, many of them end in O-S-E, as you've already sensed. 00:43:14.000 --> 00:43:18.000 So it turns out that the enzyme lactase is made in large amounts by 00:43:18.000 --> 00:43:22.000 most mammals very early in life. Why? To be able to breakdown the 00:43:22.000 --> 00:43:27.000 milk sugar that comes in their mother's milk. 00:43:27.000 --> 00:43:30.000 But once mammals are weaned there's no reason on earth for them to 00:43:30.000 --> 00:43:34.000 continue to make lactase, in their stomach for example. 00:43:34.000 --> 00:43:38.000 And, as a consequence, in most mammals the production of lactase is 00:43:38.000 --> 00:43:42.000 shut down later in life. And for some weird quirk of human 00:43:42.000 --> 00:43:46.000 history, a significant proportion of humanity has learned how to retain 00:43:46.000 --> 00:43:50.000 the ability to make lactose through adulthood. And, 00:43:50.000 --> 00:43:54.000 as a consequence, people can go and have ice cream 00:43:54.000 --> 00:43:58.000 until the age of 70, 80 or 90 without becoming very 00:43:58.000 --> 00:44:02.000 bloated. And we don't need to get into all 00:44:02.000 --> 00:44:06.000 the details, but you can begin to imagine. And what happens is, 00:44:06.000 --> 00:44:10.000 therefore, the lactase enzyme is shut down in their stomach. 00:44:10.000 --> 00:44:14.000 It depends. Sometimes they lose it at the age of 10 or 15 or 20. 00:44:14.000 --> 00:44:18.000 And then, for the rest of their lives, whenever they have a milk 00:44:18.000 --> 00:44:22.000 containing product, in fact, my son is also lactose 00:44:22.000 --> 00:44:26.000 intolerant. I'm surrounded by these people. Again, 00:44:26.000 --> 00:44:30.000 he is otherwise a tolerant person but he's lactose intolerant. 00:44:30.000 --> 00:44:33.000 So this lactose molecule will go into the stomach, 00:44:33.000 --> 00:44:37.000 it will remain undigested, it will remain a disaccharide 00:44:37.000 --> 00:44:40.000 instead of being cleaved into two monosaccharides. 00:44:40.000 --> 00:44:44.000 The two monosaccharides are no problem because they can readily be 00:44:44.000 --> 00:44:47.000 interconverted. The galactose can be readily 00:44:47.000 --> 00:44:51.000 converted into glucose, and glucose is the universal 00:44:51.000 --> 00:44:54.000 currency of carbohydrate energy. And so this disaccharide passes 00:44:54.000 --> 00:44:58.000 through the stomach unaltered and it gets into the intestines, 00:44:58.000 --> 00:45:02.000 in the small intestine and the large intestine. 00:45:02.000 --> 00:45:06.000 And it turns out we have more bacterial cells in our gut than we 00:45:06.000 --> 00:45:10.000 have our own cells in the rest of the body. Imagine that. 00:45:10.000 --> 00:45:14.000 And there are a lot of bacteria that are waiting around in the gut 00:45:14.000 --> 00:45:19.000 for just a little gulp of lactose. And they never get it because most 00:45:19.000 --> 00:45:23.000 people break down their lactose long before it gets into the intestine. 00:45:23.000 --> 00:45:28.000 But here we have these lactose intolerant people. 00:45:28.000 --> 00:45:31.000 The disaccharide gets into the gut and the bacteria go to town. 00:45:31.000 --> 00:45:35.000 They've been waiting around for years, decades for a little bit of 00:45:35.000 --> 00:45:39.000 lactose. And now it finally arrives and they go to town, 00:45:39.000 --> 00:45:43.000 ad they start metabolizing it and they ferment and they produce lots 00:45:43.000 --> 00:45:46.000 of gas and other kinds of byproducts. And, as a consequence, 00:45:46.000 --> 00:45:50.000 this makes people very uncomfortable. Just to show you, 00:45:50.000 --> 00:45:54.000 now, the fact is that lactose intolerance people can perfectly 00:45:54.000 --> 00:45:58.000 well break down sucrose, obviously. This is one of the great 00:45:58.000 --> 00:46:01.000 energy sources from plants. But they cannot break this down. 00:46:01.000 --> 00:46:05.000 And I emphasize that point to indicate that the stereochemical 00:46:05.000 --> 00:46:09.000 differences between different kinds of carbohydrates makes a very 00:46:09.000 --> 00:46:13.000 important difference. An enzyme like sucrase will break 00:46:13.000 --> 00:46:17.000 down the sucrose but it will not touch lactose. 00:46:17.000 --> 00:46:21.000 So there's a high degree of stereospecificity as it's called in 00:46:21.000 --> 00:46:25.000 the trade. Here we now go to another step forward that we're 00:46:25.000 --> 00:46:29.000 going to pursue in much greater detail next time. 00:46:29.000 --> 00:46:33.000 Because here, for the first time, we talk about polymerization. We're 00:46:33.000 --> 00:46:38.000 making polymers. Where the large number of hydroxyl 00:46:38.000 --> 00:46:43.000 groups on these monosaccharides affords one many opportunities to 00:46:43.000 --> 00:46:48.000 make very long linear aggregates end-to-end like this or even side 00:46:48.000 --> 00:46:53.000 branches. If you imagine that each one of these hydroxyls, 00:46:53.000 --> 00:46:58.000 in principle, represents a site for possible esterification, 00:46:58.000 --> 00:47:03.000 i.e., the formation of a bond to a neighboring side chain. 00:47:03.000 --> 00:47:08.000 Here we see these two linear chains and here we see the branch which is 00:47:08.000 --> 00:47:13.000 afforded, which is made possible by the availability of these unutilized 00:47:13.000 --> 00:47:18.000 hydroxyl side chains which are just waiting around to participate, 00:47:18.000 --> 00:47:23.000 if the opportunity allows them, in some kind of esterification 00:47:23.000 --> 00:47:28.000 reaction to form a covalent bond. Here is, by the way, glycogen, 00:47:28.000 --> 00:47:34.000 which is the way we store a lot of sugar in our liver. 00:47:34.000 --> 00:47:38.000 Here's a starch, which is what we get from many 00:47:38.000 --> 00:47:43.000 plants. And here's another very interesting polysaccharide. 00:47:43.000 --> 00:47:47.000 It's called cellulose. And we cannot digest cellulose, 00:47:47.000 --> 00:47:52.000 but termites can. And why they can is something we'll have to wait 00:47:52.000 --> 00:47:56.000 until next time to learn about. Have a great weekend. See you on 00:47:56.000 --> 00:48:01.000 Monday.