Hi students. So this lecture that I've recorded is the one that should be um for Wednesday on the last part of chapter 3 sections 3.7 focusing on nucleic acid. Now I'm going to continue where I left off in our exploration of organic compounds and we're going to go into the fourth and final major class of the macroolelecules nucleic acid. Now these nucleic acids are fundamental for uh life as they store and transmit genetic information. So let's start with a recap of what we've covered so far. Remember there are four main organic molecule components. The first one that we've talked about was carbohydrates. These are sugars which are quick energy source. They're composed of carbon, hydrogen and oxygen. They typically form long chains and remember you have your monomer that can become a polymer by dehydration synthesis. The removal of water um combines your monomers and as I said they serve as an energy source and also structural components. From there let's go into our lipids. Our lipids are hydrophobic which means they're water filling fearing. These include your fats, your oils and your steroids. But unlike the other components, lipids are not true polymers. They're essential for things like cell membrane and also for long-term energy storage. Then last uh Monday we covered proteins and these are your polymers of amino acids. We discussed how the sequence and properties of amino acids determine protein structure and function. remember that it's the R group where the functional group determines the properties of these proteins. And so today we're going to focus on nucleic acids which are polymers of nucleotides. As noted on this slide, each bond holding monomers together has a unique name and we'll see that the nucleic acid are connected by a specific bond known as a phosphodiester bond. So the key concepts that connect all of these is polymerization through dehydration synthesis. The same process we've talked about for carbon carbohydrates and for proteins apply also to nucleic acid formation. So just a quick reminder carbohydrates follow a general formula in which you have CN H2O N where N is a whole number. And remember carbohydrates, the name stands for carbon containing compounds that are hydrated. And so most carbon atoms are linked to both a hydrogen atom and also a hydroxal group giving them their characteristic properties. So as a reminder, we classify carbohydrates into three main categories. We have our most simple form monoaccharides, which are the simplest sugar. The basic one we know is glucose. We have our disaccharide composed of two monossaccharides. As you can see here, glucose and fructose during a process of dehydration synthesis or um a condensation reaction. Um removal of water gives you a sucrose which is a disaccharide. And as you can see there, there's the gly glyosidic bond. And then we also have polysaccharides which contains many monossaccharide units. A quick rundown of our lipids. Lipids are hydrophobic. They include triglycerides which are the basic form which the glycerol is bound to the three fatty acids. And they can also come as saturated or unsaturated based on if there is a carbonarbon double bond and how many carbonarbon double bonds there are. And then you also have phospholipids. These are the ones that have both a hydrophilic and a hydrophobic region. The polar head polar remember is water loving because it's charged. Non-polar has equal sharing and therefore is uncharged and it's hydrophobic. And then you also have steroids. Remember steroids are unique because they have the characteristic four ring carbon structure. Now we go into proteins which we talked about on Monday. Remember that proteins are made from their basic monomers which are amino acid. There are 20 different amino acids and they're based the properties of them are based on the R group or the functional group. You don't need to memorize this table, but you should be able to recognize that these amino acids can be non-polar and hydrophobic or they can be polar and hydrophilic based on what's in the R group. Then you have these um charge amino acids and they could be acidic or basic depending on if you have a negative charge or positive charge. Now these um functional group or the R group on here is um boxed in blue and these are what gives the characteristics of the protein. So proteins have four levels of structure. We start with the primary structure which is the amino acid sequence uh in a linear fashion. Then the secondary structure which includes both the alpha helyses and the beta sheets. And remember the secondary structure is based on the hydrogen bond. The tertiary structure is the overall 3D folding and this is mainly based on the R group and the interaction of the R group. And lastly, not all proteins have it but some have a quattinary structure where multiple protein subunits combine to form a larger protein. So then we'll round up our lecture grouping on organic molecules talking about nucleic acid. In this case, nucleic acids are where you have polymers of the nucleotides. Nucleotides are the mon form and the nucleic acid is the polymer form. So, as you know in lecture, I don't usually read over the learning objective because um we're always usually short for time. Same here. I won't read through this, but understand that we're building on to what we've previously disc um covered talking about the small subunits, the monomers and dehydration synthesis and how you build on to make the polymers. So before we dive into the structure, let's understand why nucleic acid matters. Now genes are made of DNA and genes code for proteins. The amino acid sequence of every polyeptide is programmed within these genes. And so your complete DNA sequence or your genome contains all the genetic information that makes you unique. And so looking at this diagram, we can see that uh is showing gene expression. In step one, you have DNA that is then in the nucleus and it's used to synthesize uh messenger RNA through a process called transcription. And so the reason for it is DNA is extremely large. It doesn't leave the nucleus. So it transcribes into a smaller form that's known as messenger RNA. And then the second step the messenger RNA leaves the nucleus through the nuclear pore and then from there it's in the cytoplasm. Once it's in the cytoplasm it's in step three the mRNA is read or used by ribosome to synthesize protein and this process is known as translation. So this entire process converting the information that's stored in DNA into functional proteins that carry out cellular activity. And so here's a perfect example of why nucleic acid structure matters. We've discussed this in on Monday's lecture about cickle cell anemia and how it's a result of a single amino acid chain and that single amino acid chain is the six amino acid where you have glutamic acid which is substitute for bivalene in hemoglobin protein. And so if you look at the difference in the two, glutamic acid is negatively um charged and so it's negatively charged which means it's basic and it's hydrophilic which is water loving. Now when substitute for veene because as you can see here you have all this carbon hydrogen interaction and we know that is non-polar because they're shared fairly equally. Nonpolar molecules are hydrophobic. So this changes the interaction of um the protein based on this single mutation. Okay. And so the single change alters the protein structure and function completely. Now normal hemoglobin proteins don't associate with each other to carry out oxygen um carry oxygen efficiency efficiently. They maintain kind of a normal rounded shape of the red blood cells. that because of the mutation, the hemoglobin proteins tend to form these hydrophobic interaction where they aggregate which means they clump together. And by clumping together, it reduces that oxygen carrying capacity. And what happens is you have a deformed red blood cell that's characteristically sickle shape. And the key point in all this is that the protein change ultimately um can be traced back to the change in the DNA sequence. A mutation in the DNA changes the messenger RNA which changed the protein which changes the cell function. as stated in the previous slide that point mutation um that causes the change in the amino acid as you can see here it's because of the change in the DNA sequence we'll go over what I mean by these points but so a mutation in the DNA then changes um as you can see here from the normal on the left the DNA sequence to a mutation that we'll go into further Just a point mutation changes the protein from glutamic acid to veiling. So this brings us to one of the most fundamental concept in biology, the central dogma. And the central dogma is how information flows from DNA to RNA and from RNA to protein. Now DNA can go through a process of replication to make more DNA. And as I stated before, DNA is large. it can't leave the nucleus and so it has to make smaller forms of itself and that smaller form is messenger RNA by a process called transcription. So DNA converting to um messenger RNAs through transcription and then finally we have the uh translation where RNA directs the synthesis of proteins. And so this unidirectional flow of information is in most case the DNA contains the master instruction. The RNA serves as the messenger that carries out those construct instructions and proteins are finally produced that actually do the work in the cell. So understanding this relationship is crucial because it explains how genetic information is stored in the structure of the nucleic acid bid ultimately determines cellular function. Looking more closely at what happened in cickle cell disease at the DNA level in a normal sequence we have g a g in the DNA if you're looking at the top strand and then which codes for glutamic acid as stated before. After the mutation this becomes gg which codes for veene. So this single nucleotide change just one letter in the genetic code has a profound consequence for the protein function and ultimately leading to disease and affecting human health. So this illustrates perfectly how information is embedded in the structure of the nucleic acid that through a specific sequence of nucleotides. Now let's examine the building blocks of nucleic acid the nucleotide. So nucleic acid are the polymers. We can also call them polyucleotides. The monomers are nucleotides. Now you need to have three things to three components in a nucleotide. The first one is a fivecarbon sugar also known as a pentos sugar. In RNA that's ribos and in DNA it's deoxyibbos. And it's known as deoxyibbos. As you can see here, here's an example of a deoxy ribboucleotide. And so the sugar is a deoxyibbos where in the bottom is a ribboucle nucleotide and the sugar is ribos. If you compare the two, the word deoxyibbos or deoxy basically means it's missing an oxygen compared to the ribos. So deoxy is where there's one less oxygen than what you see in ribos. And so secondly, there's also going to be a phosphate group. So we have to have a sugar and we have to have the phosphate group. And the phosphate group is usually attached to the fifth uh carbon in the sugar. And so the phosphate group gives the nucleic acid the acidic property. And we know that because there is a negative charge there. So you have a sugar, you have a phosphate group, you also have a nitrogenous base. And nitrogenous base as you can see here has a nitrogen containing um compound. These bases are actually what stores the genetic information. So looking at the example the top shows the deoxy ribboucleotide in which you have cyine cytosine as the base and the deoxyibbos as the sugar. The bottom shows a ribboucleotide in which you have uricil is the nitrogenous base and then you have ribos as the sugar. Notice how the ribos also has an extra O group in the second carbon that's missing from the uh deoxyibbos. Understanding nucleotide structure requires a knowledge of how we number the carbons in the sugar. So we usually use prime notation and so one prime, two prime etc. to distinguish the sugar carbon from the carbons in the nitrogenous base. And so the uh one prime carbon is where the base of the nitrogenous base is attached to and it's always in this up position. And then the second carbon is where we see the key difference between DNA and RNA. RNA will have the O group. DNA the D stands for deoxy which means you're losing the oxygen here has an H group. And this is always in the down position. And so this is carbon one, two, if you look here, three, four, and the fifth carbon is where the phosphate group is attached to. This numbering system is crucial because it determines the directionality of the nucleic acid strands and how they'll grow or how um dehydration synthesis where you add the the polymers to. So going more into the nitrogenous base that they fall into two categories based on their chemical structure and this is important. So we'll start off with perramdines which have a single ring structure and includes cytosine thymine and uricil. Oftent times they're denoted by the single letter abbreviation. Notice that in this um is as it's depicted thymine with a T is only found in DNA where uricil with a U is the depiction is only found in RNA. And so these are your perramitines and your purines have fused double bonds as you can see here or double rings my apologies made up of carbon and nitrogen and these include adinine and guanine depicted as a and g. So a helpful pneummonic that I came up with is pure as gold. And so pure as gold is when purines and your purines are adinine and guanine. Another way you have to know which one are single rings. If which one has a double ring and so I think of it as pure as gold you want to have two gold rings. And so let's reiterate which bases are found where. So both DNA and RNA has cytosine adinine and guanine. And so RNA only contains uricil instead of thymine while DNA contains thymine instead of uricell. And so this is one of the key difference that we'll return to when we're discussing the base pairing. Now let's talk about how individual nucleotides join together to form a DNA strand. This happens with the dehydration reaction just as we've saw with carbohydrates and also proteins. Now what you have is an adjacent nucleotide that are joined by a covealent bond and we call this a phosphodiester linkage. Specifically the O group in the three carbon or the three prime carbon of one nucleotide will then um bind with the phosphate group of the five carbon. Okay. And so it's important that when this occurs, water is eliminated and that's where the dehydration or condensation reaction comes from. This creates a very important directional property. Nucleotides always grow from the fivep prime to the three prime direction. This means that nucleotides are always being added to the three prime of the growing strand. And so as you can see here um the five prime is attached to the phosphate group and the three prime is attached to the hydroxal group. And so when you hear about the five um prime you should think of phosphate and when you hear threep prime you should think of the hydroxal group. And these phosphodiester bond creates this kind of backbone of the sugar phosphate unit. Now the nitrogenous base hangs off of this backbone. As you kind of see here, it's the blue and um the green as shown. Uh the sugar phosphate backbone provides kind of the structural stability while the base the nitrogenous base is what carries that genetic information as I've discussed before. So looking at this more detailed view of a DNA strand, you can see how the phosphodiestester bond between the three prime carbon of one sugar to the five prime carbon of the next sugar through the phosphate group. This creates this kind of characteristic sugar phosphate backbone that you can see here. Now notice how the bases adinine, enu guanine, cytosine and thymine they project outward from this backbone. And so this backbone provides the structural integrity while the sequences of the nitrogenous base which is where the information genetic information is stored. And the three the three prime carbon of one nucleotide is always linked to the five prime carbon of the next nucleotide via the phosphate group and often stated we read from the five prime to the threep prime. So let's talk more about the structure of DNA. Now DNA doesn't exist as a single strand in the cell. It forms a double helix which is pretty famous that we know by now through complimentary base pair. That just means that certain bases can form hydrogen bonds with other bases. As you can see here, we know that hydrogen bonds are depicted by the um by the dash line. And so in this case, adinine pairs with thymine and you have two hydrogen bonds where cytosine and guanine interact together and they have three hydrogen bonds. Notice the pairing always puts a purine and a perramitine together. As you can see the purine which has the two rings of the nitrogenous base is always interacting with a perramdine. In this case, the thymine and the cytosine is the perramdine and the adinine and the guanine are guanine are the purine. And this is because this is important because it maintains a consistent space in the double helix because the large purines cannot interact with each other because there's simply not enough space. So a large purine will interact with a smaller perimeitine. These paired complimentary bases are called base paired. And based pairs is where the hydrogen bond between these bases is much weaker than the covealent bond in the backbone. But collectively these hydrogen bonds stabilize the double helix structure. DNA is double stranded and it has antiparallel strands. What we mean by antiparallel strand is one will run five prime to three prime while the other strand is the opposite and we consider it running three to five prime. The strands are complimentary meaning that if you know the sequence of one strand you can predict the sequence of the other and the ratio of perramdines to purine is always one on one because they interact together in this complimentary base pair. A helpful visualization is looking at DNA structure as a twisted ladder. The two sugar phosphate backbones form the side of the ladder and then it provides the structural support. Whereas the hydrogen bond base pairs forms the rung or of the ladder carrying that genetic information. This twisted ladder structure is known as the famous double helix. The antip parallel nature means that if you're reading one side of the ladder, you're also reading down the other side. As you read up one side, you're reading down the other side. The structure is incredibly stable, but allows for separation of the strands during replication and transcription. Oftent times it's said that we read it from the fivep prime end to the threep prime end. Now let's compare DNA and RNA systematically. These difference are crucial for understanding their different function. And as we said DNA is typically double stranded. It forms a stable double helix. The sugar is a deoxyibbos. So deoxy meaning is missing an oxygen or um missing an O group on the second um two prime carbon. DNA contains adinine, guanine, cytosine and thymine which then we know that A pairs with T in a uh two hydrogen bond and G and C's are paired together in a three hydrogen bond. Now RNA is typically singlestranded though it can form complex structures and we'll talk about this later. The sugar is a ribos which has a O group in the se the two prime and the threep prime carbon. RNA contains adinine, guanine, cytosine and uricel. So anywhere where there's thamine and DNA in RNA in the case is would be replaced with uricil. And in this case A's and U's match up and G's pairs with C. They're still A and U have the double hydrogen bond where G's and C's still have the triple hydrogen bond. And so it's important to note that this extra O group in uh the RNA's sugar ribos um makes RNA less stable than DNA because it's necessary because it can participate in additional chemical reaction. This is important later on because it causes it to be a little bit more uh unstable which is an advantage for RNA's function. RNA needs to be made and degraded quickly for um different cellular conditions. This is another way of looking at it in this table. The components as you can see here you have the nucleotide monomer. Remember what we said? The three things you need to have to be a nucleotide is you have to have a pentos sugar, you have to have a nitrogenous base and you have to have a phosphate group. Now the difference between DNA and RNA is the different sugars and also the nitrogenous base in case of DNA is CG A T where in RNA is CG AU. RNA is single strand, DNA is double strand. DNA's primary function is to store hereditary information and so it has to be stable over a long period of time. Whereas RNA has various functions to it in gene expression including carrying instructions from the DNA to the ribosomes for protein synthesis.