 Good morning. Let me also welcome you to Biology 1A and back to campus. This is your first day of classes. I always like this class the first day because everybody's here. And you'll notice that today and then you'll come next Monday and you will notice a lot of people aren't here. And I'll talk about that. Mike has talked a lot about the syllabus, so there isn't much more I want to say about the syllabus. But please look at it because there's useful information in there, particularly when the exams are. And this little section on page 3 how to do well, I cannot stress enough the point of keeping up with the material in this course. We move very quickly. I have 14 lectures and I have to be finished by my 14th lecture because Bob Fisher comes after me and I can't borrow a lecture to finish up. So we move very quickly. Now a lot of you, I can tell you what you're going to do. We webcast our lectures. They're not simulcast anymore, but they are on the web. And if you don't know how to look them up on the web that is also presumably in the syllabus. But what students do is they don't come to lecture. I understand it's easier to watch the webcast at 4 o'clock or 8 o'clock at night or 10 o'clock at night than get up at 8 o'clock in the morning. But you tend to slide back and don't watch those lectures until the weekend before the midterm. And then all of a sudden you're faced with 10 or 12 lectures with an enormous amount of material. And some of you may do alright, go get through that material and understand it. I would say most of you don't do alright. So by not keeping up with the material, you are building up sort of this backlog of material that you're going to have to deal with. You also lose the advantage of coming to office hours on a regular basis and getting your questions answered. So we think the webcasts are great as long as they are used as an auxiliary to the lecture. That is come to lecture. And then if you're going over your notes and you don't understand something because you fell asleep during that part of the lecture or whatever, go to the webcast and clarify that material. The other thing Mike stressed is we have office hours and availability for you on a regular basis. I put all my information up there, my office address, my phone number, my email address. I will have office hours every Monday, Wednesday, Friday after lecture from 9 to 10. I will also have office hours on Tuesday and Thursday from 9 to 10. If you can't make any of those office hours and want to get material covered with me, let me know. People walk down from here to VLSB. The office hours are held in 2084 VLSB. After lecture, people walk down and ask me questions. That's fine. If you see me walking across campus and you want to ask me questions, that's fine. I also go to the gym, RSF, every morning at 6 a.m. before lecture, 6 to 7 on lecture days and 6 to little later than 7 on Tuesdays and Thursdays. I have had students come up to me at the gym and say I didn't understand this thing you were talking about, protein structure. That's fine. That's good. I believe me. I'm at the gym every day, the weekends too. Not at 6. They don't open at 6. It's important for you to keep up with material. As Mike said, those of us who teach this class, we do it because we enjoy doing it. I have taught it for 20 years. Nobody makes me teach this class. I teach it because I like the material. I think biology is a fantastic subject and really exciting and I like the students. You guys out there. So I continue to teach this class. We like students, believe it or not. All of us. Myself, Bob, and John, we really do like students and we like teaching students. So this is why we're involved with this class and we think it's a very good class. It's a demanding class, but if you put the effort in, you're going to do okay. I think we all do a good job at trying to tell you what we expect out of you from the lecture material. This booklet, this green booklet, is very important for my lectures. I cover the material that's in those 50 or 60 or whatever number of pages. So it's absolutely important for you to have that booklet, bring it to lecture, and I will be referring to figure one, figure two, et cetera, down through the book to figure 130-something. And when it comes to my exam, I sit down with that booklet and I look at those figures and I create my exam questions from the figures that I have lectured from. So whatever it's called, lecture, course reader or whatever is absolutely important. I don't use PowerPoint. I use the blackboard. Some of my figures that I draw are terrible because I'm lousy. Handwriting will never be as clear as this because I had some time. I do get here early before lecture and I try to put on this far board what I will be covering and other important announcements. So if you wander in here and you want to know what's going on today, look at this board. It tells you we're going to talk about molecules and macromolecules. Office hours will start on Monday and there's one handout, the syllabus, okay? I talk fast. I'm sorry. Any questions? You can ask questions. If I see you, I will answer them. It's very hard in this room to see students and it's very hard to see when hands go up. Yes? No. No. Those are the five subjects that I will lecture on, okay? There are five different subjects and they're broken down by these titles. In the lecture handout, you will notice at the end of each section there are what I call study questions. These are questions that some of them are trivially simple, but they are a general review of the topics in that particular section. I structure my exam in this order. In other words, I'll talk about this subject. There are questions on this and this, just like that. That, I think, makes it a little easier for you. Okay. Yes? Four to one C. It's a little office inside a lab. Don't be intimidated. If you ever have to go into a lab, go into the lab. The first thing we like to point out in here is on page one of the exam of the lecture reader. And that is the chemistry requirement. We, I assume you've all had chemistry. We assume you all have chemistry. Yes? I don't think we've, no. We've never used eye clickers. I protest against eye clickers. I don't know why. Maybe someday somebody will want to try it, but I'm not going to do that. Okay. The chemistry requirement is clear. What we expect you to know in a general way is shown on that first figure. For my part, what I expect you to know is something about ionization, what that means, something about bond strength, what that means. More importantly, the functional groups in organic compounds. We're going to be talking about basically organic chemistry, sugars, amino acids, nucleic acids. You have to know when I say what an alcohol is and what an aldehyde is and what an ester is. We don't spend any time giving you the background of organic chemistry. Later on in the last portion of my lectures, these two subjects, we will be talking about oxidation reduction processes generating energy. And if you aren't familiar with oxidation reduction, that's going to be difficult. Okay. Another thing we talk about which is very important is phosphate and phosphate bonds. So things like that which are summarized on page one are pretty important. So as I said, the first subject that I talk about is biological molecules. And if you look at all living organisms, interestingly, the composition of these organisms in terms of what you find in a bacterium, a plant cell, an animal cell is very similar. And that's shown on figure two. That's a pie, pie-shaped figure. And the interesting feature of the pie-shaped figure to the left, and I can draw this one for you because I can draw a circle, is essentially three fourths of this is water. So if you look at any living organism, it is primarily composed of water. And this is, of course, when they send probes on to Mars or the moon, the first thing they're looking for is water because the belief is that there's no life living organism that will exist in the absence of water. So if there's no water on the moon, there's no life forms as we know them on the moon. Same for Mars. The rest of this pie shape is primarily biological macromolecules. About, oh, I don't know, this is 75%, roughly. This may be another 20%, which would be biological macromolecules. And then the rest, some 5% or 10%, are small metabolites or they're ions and things like that. Since we are primarily water, I think it's worth me spending, oh, 5 or 10 minutes talking about water and using this to introduce a couple of subjects that will be important when we talk about the structure of molecules. Water appears to be a very simple molecule, H2O. So you've got oxygen and two hydrogens. The interesting feature of water is it's a molecule that has a polarity. This end of the molecule has a partial negative charge. This end of the molecule has a partial positive charge, the hydrogens. What this allows water to do is to form basically a linear structure. Water in solution is structured in terms of hydrogen bonds between oxygen and hydrogens. And this is shown better in figure 3A than I could draw it on the board. Hydrogen bonds would be something like this with a hydrogen here. And it goes on and on. So that water in solution is not just an individual water molecule, but it's this lattice of water molecules that are interacting through hydrogen bonds. Hydrogen bonds are weak bonds. The strength of hydrogen bonds are approximately 1 to 5 kilocalories per mole. And this contrasts with covalent bonds, which are approximately 100 kilocalories per mole. 20 times stronger. So these are weak bonds. And it's important you'll see that hydrogen bonds play an important role in the structure of proteins and the structure of nucleic acids. And particularly within proteins, enzyme structure is very important, is very critical, critically uses hydrogen bonds. The reason these bonds are important is they're weak and they can be broken and reformed relatively easily. This lattice structure that exists for water in solution gives water a lot of very unusual properties, most of which I won't talk about. Those of you who have had... How many people have had Bio 1B? Fair number. Well, I know Lou Feldman spends a lot of time talking about how the water gets from the bottom of the tree to the top of the tree. That's because of hydrogen bonds. The feature of this structure that I want to talk about is the interaction of water with other molecules. And that's shown in figure 3C on page 3. Molecules that can hydrogen bond or interact with the charges of the water molecule, such as ions. Ions are charged species. If you've got this structure, and this is positive and this is negative, if you have another positive species, an ion, for example, a sodium ion, I guess is shown in the figure, sodium chloride is being shown, that is soluble in water because it can interact through hydrogen bonding or ionic bonding with the polar water molecule. Molecules that readily dissolve in water are known as hydrophilic molecules, which means water-loving molecules. So in biological systems, ions, sodium chloride, magnesium, potassium ion, all of these things are highly soluble in water because they are charged. There are other kinds of molecules, organic molecules, that contain hydroxide groups, OHs, sugars, for example, as we'll talk about probably on Monday. They are easily dissolved in water again because of the interaction of polar regions in the molecule with the water molecule. There are, however, some types of molecules that are not very soluble in water. Those of you who make salad dressing using oil and the vinegar, acetic acid, no oil and water don't mix. Oil and water don't mix because the oil molecules are highly insoluble in water. They don't have any polar groups. Try to dissolve benzene in water, it doesn't dissolve. You get two layers. Molecules that don't dissolve in water are known as hydrophobic, water-hating I guess, and it turns out that there are a group of molecules in biological systems that are relatively insoluble in water. So all of a cell is not soluble in water. There are, for example, membranes, which are little barriers around a cell and within the cell, which are made of hydrophobic substances and prevent water and other charged molecules from crossing that membrane. So you've got two classes of interaction with water. There are molecules that are readily soluble in water, molecules that are really insoluble in water. Both of these are found in biological systems. And we'll talk about these molecules in much more detail over the course of next week. Now, when you look at this pie-shaped figure where you remove the water and you look at what's left in this circle, that is, what's the nature of the biological molecules and what are the components that we talk about in terms of biological molecules? You can see this again in figure two that, oh, this time I guess it's like this. Some 60 to 70% of the biological molecules are made of proteins. Clearly, the largest component in a biological cell is the protein, various proteins. Then there are sort of three other compounds. There are lipids. There are carbohydrates. And there are nucleic acids representing the remaining 30% or so. I think you can see the importance of proteins in terms of cells and cell function by this very simple representation of what one finds in living organisms. I'm going to start talking about proteins today. And I spend a lot of time on proteins for a variety of reasons. One is proteins are the largest cellular component other than water. Secondly, proteins play an enormous variety of functions, roles in a cell. And I think proteins are the most interesting macromolecule, large molecule in the cell. I've worked for, you know, 40 years or more on proteins, various protein structures and functions. So proteins are pretty important. You'll hear much more about nucleic acids in the second portion of this class when Bob Fisher lectures. So I don't talk that much about nucleic acids. If you look at figure four, it shows something important about the kinds of molecules that are found in cells. These molecules are in general, they are macromolecules, we call them macromolecules being large molecular weight components. And this one, this one, and this one, and I can even put them in boxes, are generally found as high molecular weight polymers which are built up from lower molecular weight individual units. That's what's shown in figure four. So sugars or carbohydrates are polymerized through the addition of sugar, individual sugar units to form polysaccharides. Amino acids are the building unit of protein. So one takes an amino acid or a number of amino acids and puts them together to make a protein. One takes a nucleotide and puts a number of those together to make a nucleic acid. The monomeric unit is different. In this case it's a monosaccharide, in this case it's a nucleotide, in this case it's an amino acid. Now I've left lipids out of this because lipids are a little different. Lipids don't form high molecular weight polymers, although they form something which is bigger than the individual components. For example, in a fatty acid one has a glycerol molecule and a carboxylic acid. We'll talk about that, but there are no high molecular weight polymers that are formed in relation to lipids. The kind of bonds that are built up as you make these polymers varies and we'll talk about that in much more detail. Some of the types of molecules are summarized in table 5. Table 5 is kind of a useful table. Here's an example and I'll keep making this point over and over where you should look at this table and don't memorize it. I cannot emphasize enough to you. Please don't memorize very large complicated tables. Do not memorize chemical structures. We're going to go to a figure very quickly on the next page on page 5 where all of the amino acid structures are given. I don't want you to memorize those structures. I'll tell you what I do want you to know. Later on we're going to be dealing with the structure of DNA and RNA. Nucleic acid is the same thing. I don't expect you to memorize all of the bases that are forming DNA and RNA. There are some things you have to know. There are some things you have to understand but you don't have to memorize these structures. You're all going to take MCB 102 or MCB 100 which is the basic biochemistry molecular biology course. You'll have ample opportunity to memorize chemical structures there if it's the same as it used to be. An example of what we're doing when we're making these polymers amino acids have a molecular weight of about 100 Doltons. If you take 50 amino acids you will make a protein that has a molecular weight of 5000. If you take 500 amino acids you will have a protein that has a molecular weight of 50,000. There's no average molecular weight for a protein but it's not unusual to find proteins with masses of 50,000 to 100,000 or larger so what you're doing is you're taking a large number of amino acids putting them together to make a protein. Now the question that often comes up is how many amino acids does it take before you call it a protein? It depends who you're talking to. Probably 5000 would be a 50 amino acids or something. People will start to call that thing a protein. Below that they give it a different name but there's no rhyme or reason to say the cutoff point for calling a polymer a protein is 3800 or 4000 or 5000. That doesn't exist. When we synthesize these polymers fortunately for you it's very simple. If you look at figure five it shows how two monomeric units in this case sugar molecules are being condensed to form a disaccharide. The sugar units are monosaccharides. They react together, water is split out and a disaccharide is formed. In this case, I'll put this on the board, so proteins contain amino acids and these amino acids are linked by peptide bonds and we'll go through this in more detail. Polysaccharides which are the polymers of carbohydrates contain monosaccharides and the bonding are glycosidic bonds, glycosidic. If you can't read what I write, if you can't hear what I say you're going to have to yell and scream. And nucleic acids, the units here are nucleotides and the bonding is called phosphodiester. Bonds. So this is sort of a, and then we've got the lipids which I'm just going to leave open here and open here because they're different enough so that we don't include them in this table. So in each of these cases one is taking a single unit such as a nucleotide or a monosaccharide and amino acid condensing it with another amino acid, monosaccharide or nucleotide splitting out water and synthesizing, in this case it's a dimer and then you continue doing this until you get a high molecular weight polysaccharide. The synthesis of these compounds requires energy. The reaction is reversible, it's shown in that figure five. You can break down these compounds, these high molecular weight compounds if the synthesis requires energy the breakdown releases energy. For example when we digest sugars or proteins we are releasing energy to ourselves that can be used for the synthesis of other molecules and materials. So there's this synthesis and degradation that occurs in all biological systems. Okay, in the next five or ten minutes, oh the other thing I have to mention, this is important, at nine o'clock this stage rotates. Do you know that? Have you ever seen it rotate? And the chemists come streaming in. There's chem1a follows this and they are unforgiving. They'll trample you and they'll run you over. So I have to get off the stage otherwise I disappear in the back. So I can't linger around on the stage very long. So if I'm a little short with you you know why. Because the chemists are much more aggressive than the biologists. The first year I taught this course there was a professor who followed me and he gave me a lecture, the first lecture he lectured me. He said you have to be off of that stage at nine o'clock because we have to stop. The chemistry people are in the back. They're setting up the material for their lectures. They do a lot of demonstrations. Do not be afraid if you hear an explosion. Every now and then there's, you hear a boom and somebody will appear at the door and say, it's alright, don't worry about it. But they're back there, this is a three way stage. So they're back there setting up for the chemistry. Okay, what I'm going to talk about is proteins. And as I said, I think proteins are really neat. The basic unit when we talk about proteins is the amino acid. And an amino acid looks like this. It's got an amino group. It's got a central carbon which has a hydrogen on it. It's got a carboxyl group and it has an R group. It has a side chain. And what makes amino acids different is the nature of the R group. So every amino acid has an amino group, a carboxyl group and an R group. I've always included this little figure seven because it comes back later to sort of haunt us. Clearly, if I've got an amino group and a carboxyl group, for example, carboxyl, depending on the pH, can lose a proton. This is a pH, it can ionize. And it shows you figure seven at various pHs what form of the amino acid exists. Besides the carboxyl and the amino group, the amino group can gain a proton and become positively charged. Some of the side chains that we're going to talk about can also lose or gain protons that has become positively charged or neutral. And this turns out to be very important in the structure of proteins and the structure and function of enzymes which we will talk about in great detail. So you should be aware that you can ionize the carboxyl, ionize the amino group and ionize some of the side chains that have, for example, carboxyl groups in them. And that may come into play when we talk about the structure of proteins. Okay, there are in proteins, I don't know if this is good or bad, there are 20 amino acids, 20 different amino acids that are found in proteins. Now there are probably thousands of amino acids that exist out there in the world, but only 20 amino acids are found in proteins. Not all 20 are found in any one protein, some have maybe missing several, but the maximum number of different amino acids that you will find in protein is 20. So I suppose that's good because ultimately you only have to learn 20 structures. The amino acids are grouped together based on the properties of this R-group side chain. So you can see in, see this is why you have to have this book. You look at the top of that figure 20 and it says amino acids with electrically charged hydrophilic side chains. I've told you what hydrophilic means, hydrophilic means that they are going to interact strongly with water. So you might expect those side chains to have positive charges or negative charges. And if you look through these compounds you can see there are some of them have positive charges because they have an amino group in this R. So you may have something that goes up, up, up, up and then there's an NH2 that can be positively charged. There is also a series of amino acid side chains which are negatively charged, glutamic acid and aspartic acid. They do not contain this, but they will have an R-group that has a carboxyl group on it and that carboxyl can be ionized. So these side chains have the capacity to have a charge in them. Then there are a series of amino acid side chains which don't have charged groups but they may have OHs or they may have SHs. And these are still hydrophilic because these are electron-rich compounds and they can bond very strongly with water. The classic example is serine, the amino acid side chain serine. This is the R-group in serine, CH2OH. That is shown, let me just give you the right structure. That's the serine R-group. So that oxygen makes this a very hydrophilic side chain. We'll deal with special cases in a minute. Then there are a number of amino acid side chains which are what we would call nonpolar and we would also now use the term hydrophobic. These are amino acid side chains that have no charges. They have no oxygens, they have no sulfurs. They're basically hydrocarbon-like. The best one to look at is something like isoleucine or leucine where you have just carbon atoms. So that's a side chain that is not going to interact very well with water. There are also some what we call special cases. The most important one that I want to talk about is the amino acid side chain cysteine which has a CH2SH. Its side chain has a sulfur. This sulfur can react with another sulfur and another cysteine and what would have is this and you can remove these hydrogens and you get this thing. You get a sulfur-sulfur bond. This amino acid is known as cysteine. This is cysteine. We'll talk more about this kind of structure in molecular structure of proteins. They're very important. The others are not all that important. What I want you to appreciate in terms of the structure of amino acids is how these things are grouped. What are the features? What's the basis of putting an amino acid in say the hydrophilic side chain group or the hydrophobic side chain group? And then after we talk more about protein structure I want you to be able to appreciate how these amino acid side chains are going to organize themselves within the protein. Because when proteins are formed they form a three dimensional structure that is essential to their activity. And to form that three dimensional structure there's interactions of side chains of amino acids. Okay, last thing. If you look at figure nine, figure nine shows how you make a peptide. That is you take amino acid one, AA1 and AA2. In this case it's a glycine and analanine and the carboxyl group on one amino acid reacts with the amino group on the other amino acid. So I'm just going to abbreviate this. R1, R2, I'm just drawing what's in the... So what you do is you split off water H2O. That's this condensation reaction. Water is split off and the structure that's formed which I won't put on the board here is a peptide bond where one amino acid is linked to a second amino acid. On one end you've got an amino group which is still free. On the other end you've got a carboxyl group which is still free. Every protein has an amino end which is called the N terminal end and a carboxyl end which is called the C terminal end. So there's always a free end here and a free end here. This carboxyl will react with another amino group and another amino acid to build this polymer up until you have some, you know, 500 amino acids which becomes a protein. Okay, I think this is a fine place to stop and on Monday we're going to continue. I'm going to talk about what happens when you have this protein built up and how does it obtain its real structure.