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Introduction to Nucleic Acid Biochemistry

Zee Town TV28:11

Transcription

Good day, students. You are welcome to another lecture episode on Introduction to Nucleic Acid Biochemistry.

So, when we talk about nucleic acids, we are going to be discussing the molecules that are genetic carriers, or the carriers of genetic information. And we have two types of, uh, genetic carrier molecules—molecules that carry genetic information. Uh, we are talking about DNA and RNA. So these are the two types of nucleic acid that we are going to be, uh, discussing.

First and foremost, we talk about DNA. DNA is a molecule that is found in almost every living cell. It serves as hereditary material containing biological instructions. It contains biological instructions that make each human and other organism unique. So, it—DNA—it helps the cell to make proteins, and it also helps in facilitating reproduction. It has—from the structure you can see—it has a twisted helical structure, and it is double-stranded. It means two strands, uh, are joined together, and it has, uh, some nucleotides that pair with each other. It has adenine that pairs with thymine, and guanine that pairs with, uh, cytosine. Adenine and thymine bond—it is connected via two hydrogen bonds—and guanine pairs with cytosine via three hydrogen bonds. So we are going to discuss that in detail.

DNA stands for deoxyribonucleic acid. Deoxyribonucleic acid. And it is a chemical substance that is present in the nucleus of all cells in living organisms, and it controls chemical changes that take place in the cell. So, cells in the body—you know, different cells specialize to form different tissues—and for each of those cells, we talk about myocytes. These are cells that are found in the muscles. So, cells that form muscles, and oocytes that are found in the blood. We have blood—has—we have the white blood cells and the red blood cells, and we have the nerve cells also. And all these cells that are formed, they are controlled by the DNA.

So, when we look at the DNA molecule in its entirety, it is a very large molecule that is made up of a long chain of subunits. So, DNA molecule, uh, is very long—a long molecule that is, uh, made up of what? Tens of subunits. And these subunits are what we call the nucleotides. So the subunits are called nucleotides, and each nucleotide is made up of a sugar that is called the deoxyribose. It is a five-carbon sugar that is called deoxyribose. So it means it does not contain OH at position two of the sugar, and it has also a phosphate group and an organic—an organic base—nitrogenous base.

So, nucleic acids and nucleotides—when we talk about nucleic acids, we are generally referring to the DNA and the RNA. DNA—deoxyribonucleic acid—and RNA—it's ribonucleic acid. They are the carriers of what? Genetic information. And the nucleic acids, they are biological polymers that are made up of nucleotides, and—and they also call—they also have pentose sugars—aldoses—that are linked to the purine or pyrimidine base and also a phosphate group.

So, when we say purine molecules, we are talking about those nucleotides that made up the, uh, the—that's made up—the cells—that is the building block of the DNA. And also we have the—the—the pyrimidines. So, for the purines, the purines are examples of—purines are adenine—rather, examples of purines include adenine and guanine. So adenine and guanine are purines, while pyrimidines include cytosine, thymine, and uracil—CTU, okay, CTU—for pyrimidines, and AG—adenine and guanine—serve as, uh, as purines. So, for adenine, it is abbreviated as A, guanine abbreviated as G, cytosine abbreviated as C, thymine U—uracil U. So that is why the genetic code—you—is represented as ACTG and so on and so forth. So, for DNA, you have your ACTG, according to the combination, depending on A pairs with T and G pairs with C. While in RNA, you have—you don't have T in RNA; rather, you have what we call uracil, okay. So uracil replaces thymine in RNA. So in RNA you are going to have—so the sugars that are found can be either the ribose or the deoxyribose, as in the case of DNA or as a case of RNA or DNA, respectively. So in DNA we have the deoxyribose, while in RNA we have the ribose.

So if we look at the structure, we have sugar and nitrogenous base to form what we call a, uh, a nucleoside. So a nucleoside is—is having sugar and a nitrogenous base—and when a phosphate group is attached to the sugar, we have what we call a nucleotide. And many of these nucleotides come together—this is the monomeric unit—the nucleotide—to form the polymeric nucleic acid.

So the heterocycles that are found in DNA and RNA, we have the adenine, guanine, cytosine, and thymine that are found in DNA, while in RNA we have uracil in place of thymine. And structurally, and this is how they look like. We have the adenine that is represented as A, can be found in both DNA and RNA. And we have the guanine that is—can be found in both DNA and RNA. And we have the cytosine that is found in DNA and RNA. Then thymine that is only found in DNA, and uracil only found in RNA. Remember, in terms of whether it is purine or pyrimidine nitrogenous base, uh, we—we said that, uh, adenine and guanine are purines, while cytosine, thymine, and uracil are pyrimidines.

So the deoxyribonucleotides that are found in DNA—for the nucleotide—and there are symbols and also the nucleotides. So nucleotides are the combination of the nitrogenous base, the sugar, and the phosphate group, while the nucleoside is the nitrogenous base, the sugar without the phosphate group, and they have their own representation. So, structurally, when you say deoxyadenosine, it is deoxyadenosine five-prime monophosphate, and it can be represented as dAMP, okay. So, um, for the nucleoside form, it is called deoxyadenosine, and it is represented as dA. For the next one, it can be represented as dGMP—that is deoxyguanylate or deoxyguanosine five-prime monophosphate—and the nucleoside is deoxyguanosine and represented as dG. So also for the thymine, you have dT for the deoxythymidine as the nucleoside. So also dC for the deoxycytidine for cytosine nucleosides, and you have the different nucleotides here represented. So for the deoxyribonucleotide—that is those that are found within the DNA—we have the two-prime deoxyadenosine five-prime monophosphate, and we have the two-prime deoxyguanosine five-prime monophosphate, as in the case of either thymidine that is here or guanine and if cytosine, we have two-prime deoxycytidine five-prime phosphate, and we have the for thymine is two-prime deoxythymidine five-prime phosphate. So this—they are found in the DNA, okay. They are the deoxyribonucleotides; they are found in DNA, while here the—the—the deoxyribonucleotides that are found in the DNA also. So it's still, uh, the same, uh, representation here.

So the hydrogen bonding interaction: two bases can form hydrogen bonds between them. For a monomer, a large number of base pairs is, uh, is possible for—in—while in polynucleotide, only few possibilities exist. So if you look at Watson-Crick base pairs, they predominate in double-stranded DNA where adenine pairs with thymine—two hydrogen bonds—cytosine pairs with guanine with three hydrogen bonds. So these are purine pairs that pair with the, uh, pyrimidine, okay.

So the building block molecule of nucleic acids are the nucleotides. In RNA, we have the CMP, GMP, and TMP, while in DNA we have the—the CMP, uh, the GMP, and the U.

Functions of nucleotides and nucleic acids. So, um, nucleotide functions: they function in, uh, for energy metabolism where ATP is the, uh, energy currency—that's the universal energy currency—and all living organisms utilize energy in the form of ATP. And they also—they are found in enzyme co-factors, such as adenine nicotinamide adenine dinucleotide serve as a co-factor for some enzymes, and also in signal transduction, such as cyclic AMP.

So for nucleic acid, uh, function—the functions in the form of storage of genetic information in DNA, transmission of genetic information in messenger RNA, in processing of genetic information—ribosomes and protein synthesis where you have tRNA, transfer RNA, and ribosomal RNA.

So the linkage between the molecules is in the form of phosphodiester linkage or phosphodiester bridge. You have the three-prime terminal and also five-prime terminal in the nucleotide residue.

Nucleotide composition is of three parts: we have the deoxyribose sugar without the oxygen in the two carbon, and we have phosphate group, we have one of the four types of bases that are all nitrogen-containing: we have the adenine, adenine, thymine that is only found in DNA, and cytosine that is, uh, found in, uh, both DNA and RNA, and guanine also.

Base pairing is based on the Watson-Crick model in 1953. If you remember from our previous, uh, lecture video on the history of science—that made scientist—that made contribution—scientist that made contribution—breakthrough in biochemistry—you remember in 1953, Watson and Crick—they noted that DNA consists of two polynucleotide strands running in opposite directions, and they coil around each other in a double helix. And the strands are held together by hydrogen bonds between specific base pairs. And adenine and thymine form strong hydrogen bonds with each other, okay, in two hydrogen bonds with each other, but not—they don't form hydrogen—means A do not pair with G or C, and T do not pair with—with C or G. Rather, C pairs with G. So G and cytosine and guanine form strong hydrogen bonds between each other, but they do not form, uh, hydrogen bonds between, uh, G and A or G and T or C and A or C and T. So the G-C hydrogen bond is three, while the A-T hydrogen bond is two. And the difference in the strands are that the strands of DNA are complementary because of hydrogen bonds, and wherever G occurs in one strand, C occurs in the opposite—in the other opposite strand, okay, because you remember—remember the double helical nature of the DNA, okay. So in the double-stranded—one strand of the DNA—if A is there in one strand, opposite to it—that they form the hydrogen bond—you must see a T that is going towards the opposite direction. So when an A occurs in one strand, a T occurs in the other strand, as simple as that.

So if you look at the base pairing and the arrangement, the phosphodiester linkage is in three-prime five-prime direction. So we look at the phosphate bridge here—phosphate bridge here, okay—that link one nucleotide—one nucleotide to another to form a continuous, uh, polymeric unit—DNA.

So the primary structure of nucleic acid: it, uh, is that you have a nucleotide—phosphate group, sugar, and nitrogenous base—that forms a—with—that reacts with another—link with another nucleotide—with the formation of an ester bond to form phosphodiester bond. So you have it—the five-prime—sorry, the three-prime O of one nucleotide forms, uh, a—a bond with the oxygen or the phosphate group of another molecule of the nucleotide in the five-prime, uh, uh, position. So you have what—the five-prime free five-prime phosphate that is ready to be attached to another nucleotide that is having the O3-prime, and you have what—three-prime O here—free hydroxyl group—that is ready to attach to another five-prime—three five-prime phosphate of another nucleotide. So that is how the molecule builds up—the polymer builds up.

So the primary structure of nucleic acid is the nucleotide sequence, and the nucleotides in nucleic acid are joined by phosphodiester bonds, and O3-prime O of the sugar in one nucleotide forms an ester bond to the phosphate group on the five-prime carbon of the other sugar that is next in the nucleotide.

Generalized structure of DNA looks like: you have five-prime three five-prime phosphate group at the end, and you have phosphate group, the sugar attached to the base, the phosphate group attached in the next nucleotide, and you have the phosphate group, sugar, base, and the three-prime and free, okay. This is how it looks like, uh, similar to what we, uh, demonstrated. So the primary structure looks like—like this—where you have A and you have C here, you have G, you have T in what—you have the—in five-prime three-prime direction or three-prime five-prime direction. And for the next strand, it will be the three-prime five-prime direction. So a nucleic acid polymer has a free five-prime phosphate group at one end and a free three-prime OH group at the other end. The sequence is read from the five-prime to three-prime using the letters of the bases—from the three-prime to five-prime—you have A, C, G, T—that's how you read it—from five-prime to three-prime. And this example reads as what? Five-prime ACGT three-prime. That is how the sequence reads. Example of DNA primary structure—the deoxyribonucleic acid here—three-prime, okay, and you have the—the adenine here—adenine is here, while here is cytosine. You have your three-prime phosphodiester bond, and you have another three-prime three-prime phosphodiester bond. So this is how it's, uh, looks like—five-prime ACGC three-prime. So in the DNA, we have ACGT are linked by three-prime five-prime phosphodiester bonds between the deoxyribose and the phosphate group.

Nucleic acid structure—the polymerization looks like this, okay. You have your A, G, A, and guanine here, adenine here, thymine and cytosine here, and you have three-prime three five-prime phosphate end here and the three-prime OH—hydroxyl group—three here. So you have a sugar phosphate backbone and you have the nucleotides, and it looks like this in DNA and also in the RNA. So you remember in DNA you have what—the deoxyribose—and while in RNA you have the ribose. So the sequences can be described as—to be said is a chain that is from five-prime and identifying the bases in order of their occurrence using the abbreviations A for adenosine, G for guanosine, C for cytidine, and T for thymidine or U for uracil in RNA. A typical sequence is written as TAGDC.

Properties of DNA: is a double helix—it's a double hel—double helical nature, and the strands of the DNA are antiparallel. It means one strand is—is opposite to the other strand. If one strand is going from five-prime to three-prime, the other strand will go, uh, in three-prime five-prime direction. G pairs with C—can see G pair with C with three hydrogen bonds—and A pairs with T with two hydrogen bonds. And the strands are complementary. There are hydrogen bond forces, okay. So the strands are complementary in that the number of G are equals to the number of C, and number of A are equals to the number of T. There are base-stacking interactions, and there are 10 base pairs per turn—before each turn—because it's—it's twisted helical—before each turn there are 10 base pairs.

So this is another representation of how the structure looks like, okay. So for the five-prime three-prime direction looks like this, while the three-prime—the five-prime three-prime in the opposite direction, it looks inverted.

Um, thank you. We are going to stop here. Uh, when we come next, we will discuss, uh, uh, more on the, uh, possible combination, uh, and also the, uh, more explanation. So if you have any question, you can drop it at the comment section, and you are, uh, going to be covered, and it's going to be addressed. Thank you. See you in the next video.