Key Concepts in Physiology and Chemistry

Hello everyone, Mr. Linder here. As you continue your study of physiology, it's important that you go back and review chemistry, as well as go back and review structures of the cell. As you're reviewing chemistry, make sure you pay attention to atomic structure. Make sure that you understand protons, neutrons, and electrons. Also make sure that you look at molecules and understand how different elements can combine together. As you also review chemistry, make sure that you are looking at bonding, hydrogen bonding, ionic bonding, covalent bonding, and then take some time to look at things like pH, solutions, and even concentrations of solutions. Another important aspect in chemistry that you should review before you continue on with your studies in physiology is just some basic organic chemistry. For organic chemistry... you want to review the structures of carbohydrates, proteins, lipids, and nucleic acids. Because as we all know, we are what we eat. So when you consume foods, you're really consuming the macromolecules that make up the human body. So it's important to know the structure of proteins and carbohydrates and lipids and nucleic acids because it'll help you further your understanding of physiology. You should also review the study. of cytology and look at cellular structure. Make sure that you're focusing on things like the structure of plasma membranes. Make sure that you understand phospholipids and cholesterol. Make sure that you're looking at the protein structure within the plasma membrane. And then it's important to go through your cellular components. If you're unfamiliar with mitochondria, rough ER, smooth ER, ribosomes, etc., make sure that you're going through and looking at those structures. I want to pick up in this lesson looking at the nucleus and really focusing on a really important physiological concept, which is DNA replication. So before we get into DNA replication, though, I want to talk a little bit about just the basic structure of the nucleus and the concept of the genome and proteome before we get into the structure of DNA. So what you're looking at right now is a nucleus and you'll notice that the nucleus has a double membrane structure and then you have these yellow structures which are the nuclear pores and the nuclear pores are what are going to allow certain items to enter and exit the nucleus. Inside the nucleus you have the nucleolus and the nucleolus contains the genetic information for the production. of ribosomes. You'll also notice the material that's dispersed within the nucleoplasm, and that material would be the chromatin. The chromatin is actually just dispersed DNA. It is associated with proteins, and we'll look further at that structure. But we also know that this material can condense down into chromosomes when we're going through cell division. So what is this idea, though, of genome? and proteome. The genome represents all of the genes that are found within the cell. It's estimated that humans have about 25,000 genes as part of their genome, and genes code for proteins. And so there's a process called transcription and translation that I'll go over in future videos that is the process for basically activating the genome. and producing proteins. So what is the proteome? The proteome is the collection of all the polypeptides, all of the proteins that are found within the human body. What's interesting is that there's estimated that there's over a hundred thousand proteins found within the human body. And so one would think, well, if there's 25,000 genes, there should only be 25,000 proteins. But it turns out that that's not the case. The proteome is actually much bigger than the genome. And so how does that happen? There's three things to consider. The first thing is that RNA that's coded by a gene could actually be spliced together in different ways. So when you take a gene sequence and you produce an RNA sequence, there are mechanisms for rearranging the RNA code. So sometimes when you get the first RNA code, you can produce one type of protein. But as you rearrange that RNA code, you can produce a different protein. And so that gives us really an ability to produce a whole host of different kinds of proteins. Think of that in terms of the immune system. When our B cells are producing antibodies, we need the ability to produce different proteins. And an antibody is a different protein. We need it. be able to rearrange the code so we can make new types of proteins to protect us against new novel viruses. Another thing that can happen is polypeptides can link with one another. So you could have gene number one producing a protein, a gene number two producing a protein, but those two proteins could come together and form a new protein. A plus B gives you protein AB. AB didn't come from one gene. It actually came from two different genes, but it allows us to produce a different protein. A third thing to consider is that you can add things to proteins. So carbohydrates or lipids can be added to proteins to modify them and make them different proteins and therefore have different functions. You've probably heard of glycoproteins. So these are modifications of molecules within the body. So when you have glycoproteins, when you have phosphorylation, methylation of different proteins, then you can have... different functionality, and so our proteome gets much bigger. So what is the chromatin? The chromatin is the dispersed DNA within the nucleus. So here we see chromatin just kind of dispersed about within the nucleus, but you'll notice that it's organized. So DNA within the nucleus will actually wrap itself around these histone proteins, and it forms a structure called a nucleosome. And so we have an organization for the DNA within the nucleus. If you were to supercoil this material, this chromatin material, you can actually produce chromosomal structures. And so chromosomes can actually be seen with a light microscope. We see this starting in prophase of cell division, and you can actually start to visualize these chromosome structures, but it's really just the tightly combined. packed chromatin. So chromatin becomes the chromosomes when it's highly condensed. So in this diagram, you can see DNA. DNA is a double helix structure. And then that DNA wraps around histone proteins to form this nucleosome. And we can keep organizing it, organizing it, supercoiling it to the point where you can actually have chromosomes. And chromosomes make for a great organizational structure. So when you're... moving things around within the cell during metaphase and anaphase, you want to have an organized structure. So histone proteins, the way they're able to help with this organization is they have a positive charge to them and DNA has a negative charge. So that negatively charged DNA is going to wrap around the positively charged histones. You probably heard the term opposites attract. So we have this. ability to keep things organized within the nucleus. So why is this all of interest to us in physiology? Well, we need to replicate the DNA when we're passing on genetic information to the next cell. So you want to make sure that there's a copy of the genetic material when you're doing cell division. And then it's also important to understand how we can activate the genes as well, since it's in this organized state. So when you look at a cell and you look at the nucleus, not all of the genes are active within a cell. When you were one cell, all the genes were active and one cell became two cells and two cells become four cells. And so it's important to have access to all of the genes because you're trying to, through embryonic development, produce bone, produce muscle, produce skin, nervous system and so forth. But when you have adult cells... they don't need access to all of the genetic information. It turns out that adult cells will only use somewhere between 300 to 500 genes depending upon what type of cell it is. So if it's a hepatocyte cell doing liver things or if it's a kidney cell or if it's a neuron, a cardiac muscle cell, they're only going to have access to the genes that they need to actually be functional. And so a lot of our genes actually go dormant in the adult cells. So how do we describe these genes? Well, we usually have a term called euchromatin or heterochromatin. Heterochromatin basically talks about the genes that are permanently inactive within the cell. And so we call that heterochromatin. Euchromatin, though, is genes that... can be used within that cell. So that would be part of that 300 to 500 genes, but they still oftentimes need to be activated in some way. So euchromatin is really active genes within the cell. We just need access to those genes because again, DNA is wrapped around proteins within the nucleus. So how do you activate genes in order to have genetic transcription? Genetic transcription is when you read the DNA and you produce RNA. So how do you get access, though, to the genetic material? So in this diagram, you can see the DNA in purple wrapped around the histone proteins. But if it's tightly packed together, it's kind of hard to read. Think of it like a scroll rolled up. If you were to unroll that scroll, though, you could actually read the material that's on the scroll. So in order to... activate the euchromatin, we have a process known as acetylation. Acetylation is basically where we add carbon subunits. These two carbon molecules are added to the euchromatin in order to start uncoiling the genetic information. And so as you begin to separate sections of DNA from the nucleosomes, you now will start to have access to that DNA. And so down here you can see there's a section of DNA that we have access to. And now once it's been acetylated and uncoiled, you can actually add transcriptional factors, proteins that are added to the DNA. And sometimes it's other things as well, but usually it's a protein receptor, maybe activated by a vitamin, maybe activated by a hormone that's going to bind to the DNA. and start the process of transcription. So a transcriptional factor is something that's going to aid in the process of transcription. And then you're going to bring in enzymes to read the genetic code. When you're going to close up the material, we have what's called deacetylation. So deacetylation is where you remove those two carbon subunits so that the genetic material will close back up. And the euchromatin, although active, will not be able to be read at this point in time. So it has active genes, but you're just not currently reading it. If you want to replicate the DNA, then you need to go through a process called DNA replication. DNA is the only molecule that's capable of replication. It's a process that has to be accurate. It has to be fast in living systems so that you can copy the genetic material and give it to the next nucleus and essentially the next cell. The DNA has to be separated and then you have to attach the appropriate complementary bases. So if you look at this diagram, when you separate a DNA molecule, you need to make sure that you are copying A's with T's and G's with C's and so forth and so forth. So when this strand of the DNA is being replicated, Notice that G goes with C, C goes with G, A goes with T, and so forth and so forth. So there has to be this complementary base pairing that takes place in DNA replication. Adenine goes with thymine, guanine goes with cytosine. The replication process is known as a semi-conservative process, meaning that the new molecules that are produced have half of the original parent molecule. So as this DNA is opened up... this is the parent molecule, and this is the new molecule that's being produced. So semi-conservative replication. The mechanism for replication is rather complex. So oftentimes when we describe physiological processes, oftentimes we're doing an oversimplification of what's actually taking place, but we get the big picture in physiology. in terms of the process. For more detail, you would definitely want to take a genetics course to get the full details on DNA replication. But to give you the main idea of DNA replication, we need to look at the action of enzymes. We need to look at helicase, we need to look at polymerase, ligase, and telomerase. So the mechanism for DNA replication is a bi-directional process. meaning that we're going to replicate the molecule in two directions. So here we have the original parent molecule in this diagram. And then we can see that the parent molecule has actually been unzipped. So think of it like a zipper. So we're unzipping it here. Now, you can actually have multiple replication bubbles. So you can actually replicate one portion of the DNA here. But you could also be opening it up down here and replicating a whole other section somewhere else along the molecule. So this can happen in multiple places. So DNA helicase, though, is the enzyme that's going to unzip the DNA. Now what you'll notice in this bi-directional though process is that the growing molecule goes in what's called a five prime to three prime direction. Now this is an organic chemistry terminology when you talk about five prime and three prime. So when you look at a DNA molecule it's a numbering pattern for the carbons. So this is the sugar that's part of the nucleotide for DNA. So this is deoxyribose sugar. Here we have a phosphate, a sugar, and a base. That makes up the nucleotide structure. And when you number in organic chemistry, we number the carbons. So this is carbon 1, carbon 2, carbon 3, carbon 4, and carbon 5 on the ribose sugar. So the orientation would be this is the 5 prime end because it's near the 5 carbon. And then down here, this would be the 3 prime end because it's near the 3 carbon. On the opposite side, DNA is what's called anti-parallel, so everything is flipped over. So you notice on this side of the molecule, this would be the one carbon, the two carbon, the three carbon, the four carbon, and the five carbon. So this is the three prime end and the five prime end. That's important for us to understand just so that when you look at a diagram, you can understand what's happening in the directionality. So there's an enzyme called polymerase that will only bind to the three prime end. and therefore it grows the new molecule from 5'to 3'direction. That's problematic on the opposite side because you're actually going away from the helicase. So as you unzip on one side, you can have polymerase following the molecule, can follow the helicase, and you can just add bases, add bases, add bases, and everything's good. But if you're going in the opposite direction, you're going away from the helicase, and you're going to have a new molecule that's going to be in the same direction. As I grow this portion of the strand, that's fine. But then as you unzip more, you have to have another polymerase come in and bind at this location. Sorry, go back. Have to bind at this location and then start growing out again until it reaches the portion that's already been done. So what happens is you get a fragmented side for replication. So you have what's called a continuous side or a leading side. And then on the opposite side, you have a fragmented or discontinuous side. which is the lagging side of replication. So let's go through the mechanism really quick for DNA replication. So if you were to write this out, you could say DNA helicase enzymes unzip the DNA molecule. Okay. So DNA helicase unzips the DNA molecule at what's called a replication fork. And so you can have multiple replication forks along the molecule. Then the enzyme DNA polymerase, DNA polymerase. will come in and it will add the appropriate nucleotides to the parent strand. So if it sees a C, it puts in a G. If it sees a T, it puts in an A. If it sees an A, it puts in a T, and so forth. Remember, though, DNA polymerase can only start at a 3'location. So it grows 5'to 3'. In doing that, it creates a leading strand and a lagging strand. So we have a leading strand on one side of the replication and a lagging strand on the opposite side of the replication. So because there's a lagging strand and there's a fragmented construction, you're going to have to link those fragments together. Those fragments are called Okazaki fragments. And so here we have an Okazaki fragment. Here's another Okazaki fragment. Here's another Okazaki fragment and so forth and so forth. The enzyme that's going to link these fragments together is called DNA ligase. So DNA ligase comes in and it links the Okazaki fragments together. So you'll have a continuous molecule of DNA. One last thing, because DNA polymerase cannot fully replicate the DNA molecule, DNA would actually get shorter with each replication. So basically, the DNA polymerase falls off the ends of the DNA molecule that it's replicating, and therefore DNA gets shorter with each replication. So to prevent that from happening, we have a specialized enzyme called telomerase. And what telomerase does is it comes along and it adds in pieces of DNA so that the DNA does not get shorter with each replication. So what is the purpose then of this telomerase? It's basically to protect against the shortening of your DNA. And that piece of material, so here we have in this diagram, this is DNA and this is a lengthened piece of DNA. This lengthened piece is called a telomere. Over here we have a short telomere. That means that telomerase activity is not taking place and so we're not lengthening this piece of DNA. We believe that the decreased ability of cells to divide over time is because their DNA is getting shorter, and therefore we're having aging of the cell. So decreased ability of cells to divide is actually a sign of aging. And this aging is probably related to decreased telomerase activity and the shortening of our telomeres over time. So what are these caps actually doing? What is this happening? telomere structure actually doing for the DNA? Well, it's preventing enzymes within the cell from considering that DNA to be broken and needing to be sort of broken down and recycled. And so it keeps enzymes from mistaking the DNA as being broken material. So the longer your telomeres are, the healthier your cells most likely are. DNA polymerase can't fully copy the ends So this telomerase enzyme has to come along and replicate the ends. And so here's how it does it. So here we have this short piece of DNA and we need to make this DNA longer. So the telomerase enzyme comes along and it uses an RNA template to link on to the DNA. And then using that RNA template, we can add in pieces of DNA. So here we have an A. going with U because in RNA you have U's instead of T's. Here we have G with C, G with C, G with C, T with A because it's DNA. So we can put T's in for the new DNA. So A gets a T, A gets a T. Here's a U again. So we would bring in that A. Oops, sorry, go back. We bring in that A, then C and G and so forth. So once you have a new strand of DNA that the telomerase has brought in, Then DNA polymerase can come along again and read that new piece of DNA and then add in the corresponding complementary bases along the bottom. And then you end up with that double stranded structure. And so what we're doing is we're lengthening that piece of DNA. Germinal cells do this and they use lots of telomerase activity. Your germinal cells would be gametes. So you're going to see a lot of telomerase activity. in sperm cells or oocytes. You're also going to see telomerase activity in stem cells. You're going to see also telomerase activity in cancerous cells as well. And that's partially why cancerous cells can continue going and dividing, having that uncontrolled cellular division because the DNA continues to be protected. So I hope that helps. Take care.

Make sure that you understand protons, neutrons, and electrons. Also make sure that you look at molecules and understand how different elements can combine together. As you also review chemistry, make sure that you are looking at bonding, hydrogen bonding, ionic bonding, covalent bonding, and then take some time to look at things like pH, solutions, and even concentrations of solutions. Another important aspect in chemistry that you should review before you continue on with your studies in physiology is just some basic organic chemistry.

For organic chemistry... you want to review the structures of carbohydrates, proteins, lipids, and nucleic acids. Because as we all know, we are what we eat. So when you consume foods, you're really consuming the macromolecules that make up the human body.

So it's important to know the structure of proteins and carbohydrates and lipids and nucleic acids because it'll help you further your understanding of physiology. You should also review the study. of cytology and look at cellular structure.

Make sure that you're focusing on things like the structure of plasma membranes. Make sure that you understand phospholipids and cholesterol. Make sure that you're looking at the protein structure within the plasma membrane.

And then it's important to go through your cellular components. If you're unfamiliar with mitochondria, rough ER, smooth ER, ribosomes, etc., make sure that you're going through and looking at those structures. I want to pick up in this lesson looking at the nucleus and really focusing on a really important physiological concept, which is DNA replication. So before we get into DNA replication, though, I want to talk a little bit about just the basic structure of the nucleus and the concept of the genome and proteome before we get into the structure of DNA. So what you're looking at right now is a nucleus and you'll notice that the nucleus has a double membrane structure and then you have these yellow structures which are the nuclear pores and the nuclear pores are what are going to allow certain items to enter and exit the nucleus.

Inside the nucleus you have the nucleolus and the nucleolus contains the genetic information for the production. of ribosomes. You'll also notice the material that's dispersed within the nucleoplasm, and that material would be the chromatin. The chromatin is actually just dispersed DNA. It is associated with proteins, and we'll look further at that structure.

But we also know that this material can condense down into chromosomes when we're going through cell division. So what is this idea, though, of genome? and proteome. The genome represents all of the genes that are found within the cell. It's estimated that humans have about 25,000 genes as part of their genome, and genes code for proteins.

And so there's a process called transcription and translation that I'll go over in future videos that is the process for basically activating the genome. and producing proteins. So what is the proteome? The proteome is the collection of all the polypeptides, all of the proteins that are found within the human body.

What's interesting is that there's estimated that there's over a hundred thousand proteins found within the human body. And so one would think, well, if there's 25,000 genes, there should only be 25,000 proteins. But it turns out that that's not the case.

The proteome is actually much bigger than the genome. And so how does that happen? There's three things to consider. The first thing is that RNA that's coded by a gene could actually be spliced together in different ways.

So when you take a gene sequence and you produce an RNA sequence, there are mechanisms for rearranging the RNA code. So sometimes when you get the first RNA code, you can produce one type of protein. But as you rearrange that RNA code, you can produce a different protein.

And so that gives us really an ability to produce a whole host of different kinds of proteins. Think of that in terms of the immune system. When our B cells are producing antibodies, we need the ability to produce different proteins. And an antibody is a different protein.

We need it. be able to rearrange the code so we can make new types of proteins to protect us against new novel viruses. Another thing that can happen is polypeptides can link with one another. So you could have gene number one producing a protein, a gene number two producing a protein, but those two proteins could come together and form a new protein. A plus B gives you protein AB.

AB didn't come from one gene. It actually came from two different genes, but it allows us to produce a different protein. A third thing to consider is that you can add things to proteins.

So carbohydrates or lipids can be added to proteins to modify them and make them different proteins and therefore have different functions. You've probably heard of glycoproteins. So these are modifications of molecules within the body.

So when you have glycoproteins, when you have phosphorylation, methylation of different proteins, then you can have... different functionality, and so our proteome gets much bigger. So what is the chromatin?

The chromatin is the dispersed DNA within the nucleus. So here we see chromatin just kind of dispersed about within the nucleus, but you'll notice that it's organized. So DNA within the nucleus will actually wrap itself around these histone proteins, and it forms a structure called a nucleosome. And so we have an organization for the DNA within the nucleus. If you were to supercoil this material, this chromatin material, you can actually produce chromosomal structures.

And so chromosomes can actually be seen with a light microscope. We see this starting in prophase of cell division, and you can actually start to visualize these chromosome structures, but it's really just the tightly combined. packed chromatin.

So chromatin becomes the chromosomes when it's highly condensed. So in this diagram, you can see DNA. DNA is a double helix structure.

And then that DNA wraps around histone proteins to form this nucleosome. And we can keep organizing it, organizing it, supercoiling it to the point where you can actually have chromosomes. And chromosomes make for a great organizational structure. So when you're...

moving things around within the cell during metaphase and anaphase, you want to have an organized structure. So histone proteins, the way they're able to help with this organization is they have a positive charge to them and DNA has a negative charge. So that negatively charged DNA is going to wrap around the positively charged histones. You probably heard the term opposites attract.

So we have this. ability to keep things organized within the nucleus. So why is this all of interest to us in physiology? Well, we need to replicate the DNA when we're passing on genetic information to the next cell. So you want to make sure that there's a copy of the genetic material when you're doing cell division.

And then it's also important to understand how we can activate the genes as well, since it's in this organized state. So when you look at a cell and you look at the nucleus, not all of the genes are active within a cell. When you were one cell, all the genes were active and one cell became two cells and two cells become four cells. And so it's important to have access to all of the genes because you're trying to, through embryonic development, produce bone, produce muscle, produce skin, nervous system and so forth.

But when you have adult cells... they don't need access to all of the genetic information. It turns out that adult cells will only use somewhere between 300 to 500 genes depending upon what type of cell it is.

So if it's a hepatocyte cell doing liver things or if it's a kidney cell or if it's a neuron, a cardiac muscle cell, they're only going to have access to the genes that they need to actually be functional. And so a lot of our genes actually go dormant in the adult cells. So how do we describe these genes? Well, we usually have a term called euchromatin or heterochromatin. Heterochromatin basically talks about the genes that are permanently inactive within the cell.

And so we call that heterochromatin. Euchromatin, though, is genes that... can be used within that cell.

So that would be part of that 300 to 500 genes, but they still oftentimes need to be activated in some way. So euchromatin is really active genes within the cell. We just need access to those genes because again, DNA is wrapped around proteins within the nucleus.

So how do you activate genes in order to have genetic transcription? Genetic transcription is when you read the DNA and you produce RNA. So how do you get access, though, to the genetic material?

So in this diagram, you can see the DNA in purple wrapped around the histone proteins. But if it's tightly packed together, it's kind of hard to read. Think of it like a scroll rolled up. If you were to unroll that scroll, though, you could actually read the material that's on the scroll.

So in order to... activate the euchromatin, we have a process known as acetylation. Acetylation is basically where we add carbon subunits.

These two carbon molecules are added to the euchromatin in order to start uncoiling the genetic information. And so as you begin to separate sections of DNA from the nucleosomes, you now will start to have access to that DNA. And so down here you can see there's a section of DNA that we have access to. And now once it's been acetylated and uncoiled, you can actually add transcriptional factors, proteins that are added to the DNA. And sometimes it's other things as well, but usually it's a protein receptor, maybe activated by a vitamin, maybe activated by a hormone that's going to bind to the DNA.

and start the process of transcription. So a transcriptional factor is something that's going to aid in the process of transcription. And then you're going to bring in enzymes to read the genetic code. When you're going to close up the material, we have what's called deacetylation. So deacetylation is where you remove those two carbon subunits so that the genetic material will close back up.

And the euchromatin, although active, will not be able to be read at this point in time. So it has active genes, but you're just not currently reading it. If you want to replicate the DNA, then you need to go through a process called DNA replication. DNA is the only molecule that's capable of replication. It's a process that has to be accurate.

It has to be fast in living systems so that you can copy the genetic material and give it to the next nucleus and essentially the next cell. The DNA has to be separated and then you have to attach the appropriate complementary bases. So if you look at this diagram, when you separate a DNA molecule, you need to make sure that you are copying A's with T's and G's with C's and so forth and so forth. So when this strand of the DNA is being replicated, Notice that G goes with C, C goes with G, A goes with T, and so forth and so forth. So there has to be this complementary base pairing that takes place in DNA replication.

Adenine goes with thymine, guanine goes with cytosine. The replication process is known as a semi-conservative process, meaning that the new molecules that are produced have half of the original parent molecule. So as this DNA is opened up...

this is the parent molecule, and this is the new molecule that's being produced. So semi-conservative replication. The mechanism for replication is rather complex.

So oftentimes when we describe physiological processes, oftentimes we're doing an oversimplification of what's actually taking place, but we get the big picture in physiology. in terms of the process. For more detail, you would definitely want to take a genetics course to get the full details on DNA replication. But to give you the main idea of DNA replication, we need to look at the action of enzymes. We need to look at helicase, we need to look at polymerase, ligase, and telomerase.

So the mechanism for DNA replication is a bi-directional process. meaning that we're going to replicate the molecule in two directions. So here we have the original parent molecule in this diagram. And then we can see that the parent molecule has actually been unzipped. So think of it like a zipper.

So we're unzipping it here. Now, you can actually have multiple replication bubbles. So you can actually replicate one portion of the DNA here.

But you could also be opening it up down here and replicating a whole other section somewhere else along the molecule. So this can happen in multiple places. So DNA helicase, though, is the enzyme that's going to unzip the DNA.

Now what you'll notice in this bi-directional though process is that the growing molecule goes in what's called a five prime to three prime direction. Now this is an organic chemistry terminology when you talk about five prime and three prime. So when you look at a DNA molecule it's a numbering pattern for the carbons. So this is the sugar that's part of the nucleotide for DNA. So this is deoxyribose sugar.

Here we have a phosphate, a sugar, and a base. That makes up the nucleotide structure. And when you number in organic chemistry, we number the carbons.

So this is carbon 1, carbon 2, carbon 3, carbon 4, and carbon 5 on the ribose sugar. So the orientation would be this is the 5 prime end because it's near the 5 carbon. And then down here, this would be the 3 prime end because it's near the 3 carbon. On the opposite side, DNA is what's called anti-parallel, so everything is flipped over.

So you notice on this side of the molecule, this would be the one carbon, the two carbon, the three carbon, the four carbon, and the five carbon. So this is the three prime end and the five prime end. That's important for us to understand just so that when you look at a diagram, you can understand what's happening in the directionality. So there's an enzyme called polymerase that will only bind to the three prime end.

and therefore it grows the new molecule from 5'to 3'direction. That's problematic on the opposite side because you're actually going away from the helicase. So as you unzip on one side, you can have polymerase following the molecule, can follow the helicase, and you can just add bases, add bases, add bases, and everything's good. But if you're going in the opposite direction, you're going away from the helicase, and you're going to have a new molecule that's going to be in the same direction.

As I grow this portion of the strand, that's fine. But then as you unzip more, you have to have another polymerase come in and bind at this location. Sorry, go back. Have to bind at this location and then start growing out again until it reaches the portion that's already been done. So what happens is you get a fragmented side for replication.

So you have what's called a continuous side or a leading side. And then on the opposite side, you have a fragmented or discontinuous side. which is the lagging side of replication.

So let's go through the mechanism really quick for DNA replication. So if you were to write this out, you could say DNA helicase enzymes unzip the DNA molecule. Okay. So DNA helicase unzips the DNA molecule at what's called a replication fork.

And so you can have multiple replication forks along the molecule. Then the enzyme DNA polymerase, DNA polymerase. will come in and it will add the appropriate nucleotides to the parent strand. So if it sees a C, it puts in a G. If it sees a T, it puts in an A.

If it sees an A, it puts in a T, and so forth. Remember, though, DNA polymerase can only start at a 3'location. So it grows 5'to 3'. In doing that, it creates a leading strand and a lagging strand.

So we have a leading strand on one side of the replication and a lagging strand on the opposite side of the replication. So because there's a lagging strand and there's a fragmented construction, you're going to have to link those fragments together. Those fragments are called Okazaki fragments. And so here we have an Okazaki fragment. Here's another Okazaki fragment.

Here's another Okazaki fragment and so forth and so forth. The enzyme that's going to link these fragments together is called DNA ligase. So DNA ligase comes in and it links the Okazaki fragments together.

So you'll have a continuous molecule of DNA. One last thing, because DNA polymerase cannot fully replicate the DNA molecule, DNA would actually get shorter with each replication. So basically, the DNA polymerase falls off the ends of the DNA molecule that it's replicating, and therefore DNA gets shorter with each replication.

So to prevent that from happening, we have a specialized enzyme called telomerase. And what telomerase does is it comes along and it adds in pieces of DNA so that the DNA does not get shorter with each replication. So what is the purpose then of this telomerase? It's basically to protect against the shortening of your DNA.

And that piece of material, so here we have in this diagram, this is DNA and this is a lengthened piece of DNA. This lengthened piece is called a telomere. Over here we have a short telomere.

That means that telomerase activity is not taking place and so we're not lengthening this piece of DNA. We believe that the decreased ability of cells to divide over time is because their DNA is getting shorter, and therefore we're having aging of the cell. So decreased ability of cells to divide is actually a sign of aging.

And this aging is probably related to decreased telomerase activity and the shortening of our telomeres over time. So what are these caps actually doing? What is this happening? telomere structure actually doing for the DNA?

Well, it's preventing enzymes within the cell from considering that DNA to be broken and needing to be sort of broken down and recycled. And so it keeps enzymes from mistaking the DNA as being broken material. So the longer your telomeres are, the healthier your cells most likely are.

DNA polymerase can't fully copy the ends So this telomerase enzyme has to come along and replicate the ends. And so here's how it does it. So here we have this short piece of DNA and we need to make this DNA longer. So the telomerase enzyme comes along and it uses an RNA template to link on to the DNA. And then using that RNA template, we can add in pieces of DNA.

So here we have an A. going with U because in RNA you have U's instead of T's. Here we have G with C, G with C, G with C, T with A because it's DNA.

So we can put T's in for the new DNA. So A gets a T, A gets a T. Here's a U again. So we would bring in that A.

Oops, sorry, go back. We bring in that A, then C and G and so forth. So once you have a new strand of DNA that the telomerase has brought in, Then DNA polymerase can come along again and read that new piece of DNA and then add in the corresponding complementary bases along the bottom.

And then you end up with that double stranded structure. And so what we're doing is we're lengthening that piece of DNA. Germinal cells do this and they use lots of telomerase activity. Your germinal cells would be gametes. So you're going to see a lot of telomerase activity.

in sperm cells or oocytes. You're also going to see telomerase activity in stem cells. You're going to see also telomerase activity in cancerous cells as well.

And that's partially why cancerous cells can continue going and dividing, having that uncontrolled cellular division because the DNA continues to be protected. So I hope that helps. Take care.

Transcript for:Key Concepts in Physiology and Chemistry

Transcript for:
Key Concepts in Physiology and Chemistry