Nucleic Acids.pdf

NUCLEIC ACIDS BY PROF GANIYAT K. OLOYEDE DEPARTMENT OF CHEMISTRY UNIVERSITY OF IBADAN, NIGERIA INTRODUCTION Nucleic acids are the biopolyme...

NUCLEIC ACIDS BY PROF GANIYAT K. OLOYEDE DEPARTMENT OF CHEMISTRY UNIVERSITY OF IBADAN, NIGERIA INTRODUCTION Nucleic acids are the biopolymers, or small biomolecules, essential to all known forms of life. They are informational molecules because their primary structure contains a code or set of directions by which they can duplicate themselves and guide the synthesis of proteins. They are the building blocks of living organisms. The two main events in the life of a cell - dividing to make exact copies of themselves and manufacturing proteins - both rely on blueprints coded in our genes. They are called nucleic acids because scientists first found them in the nucleus of cells. Now that we have better equipment, nucleic acids have been found in mitochondria, chloroplasts, and cells that have no nucleus, such as bacteria and viruses. All nucleic acids are made up of the same building blocks (monomers) called "nucleotides." Nucleic acids allow organisms to transfer genetic information from one generation to the next. These macromolecules store the genetic information that determines traits and makes protein synthesis possible. There are two types, Deoxyribonucleic Acid (DNA), found mainly in the nucleus of the cell, and Ribonucleic Acid (RNA) found mainly in the cytoplasm of the cell although it is usually synthesized in the nucleus. DNA contains the genetic codes to make RNA and the RNA in turn then contains the codes for the primary sequence of amino acids to make proteins. Nucleic Acid Parts: The complete hydrolysis of nucleic acids yields three major classes of compounds: pentose sugars, phosphates, and heterocyclic amines (or bases). Phosphate: An ion of phosphoric acid known as phosphate (PO43-). It is a major requirement of all living things. It is a suitable source of phosphorus which is used as phosphate ion that is incorporated into DNA and RNA. Five-carbon Pentose Sugars: There are two types of pentose sugars found in nucleic acids. This difference is reflected in their names--deoxyribonucleic acid indicates the presence of deoxyribose; while ribonucleic acid indicates the presence of ribose. The structures of both ribose and deoxyribose are shown in Figure 1. Note the red -OH on one and the red -H on the other are the only differences. The alpha and beta designations are interchangeable and are not a significant difference between the two. 1 Figure 1: Structures of both ribose and deoxyribose QUESTION Examine the structures carefully. What is the difference between ribose and deoxyribose? ANSWER Ribose has an OH at C no 2 while deoxyribose has no OH at C no 2 QUESTION Name the pentose sugar in RNA and DNA. DNA deoxyribose, RNA ribose Heterocyclic Amines: are sometimes called nitrogen bases or simply bases because the amine groups as part of the ring or as a side chain have a basic property in water. Heterocyclic Amines are derived from two root structures: purines or pyrimidines. The purine root has both a six and a five member ring; the pyrimidine has a single six member ring. There are two major purines, adenine (A) and guanine (G), and three major pyrimidines, cytosine (C), uracil (U), and thymine (T). The structures are shown in Figure 2. Figure 2: Structures of Heterocyclic Amines A major difference between DNA and RNA is that DNA contains thymine, but not uracil, while RNA contains uracil but not thymine. The other three heterocyclic amines, adenine, guanine, and cytosine are found in both DNA and RNA. For convenience, you may remember, the list of 2 heterocyclic amines in DNA by the words: The Amazing Gene Code (TAGC) or ATCG when looking at DNA. Just as there are twenty (20) amino acids needed by humans to survive, we also require five (5) nucleotides. Deoxyribonucleic Acid (DNA) holds the code or genetic information used in the development and functioning of all known living organisms. The DNA segments carrying this genetic information are called genes. DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules. DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are, therefore, anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. DNA is therefore a long spiral chain of nucleotides in two long chains that twist around each other. That twisting shape is called a double helix. This arrangement of DNA strands is called antiparallel. The spiral ladder has the ability to wind and unwind so that the nucleic acid chain can duplicate itself. That duplication process, called replication, happens every time a cell divides. Within cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. DNA is composed of a phosphate-deoxyribose sugar backbone and the four nitrogenous bases: adenine (A), guanine (G), cytosine (C), and thymine (T). In double stranded DNA, adenine pairs with thymine (A-T) and guanine pairs with cytosine (G-C). Ribonucleic acid (RNA) is a large biological molecule that performs multiple vital roles in the coding, decoding, regulation, and expression of genes. Together with DNA, RNA comprises the nucleic acids, which, along with proteins, constitute the three major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but is usually single-stranded. Various types include mRNA (messenger RNA), tRNA (transfer RNA) and rRNA (ribosomal RNA) which work together to help cells replicate and synthesize proteins. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins, while many viruses encode their genetic information using an RNA genome. Some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function whereby mRNA molecules direct the assembly of proteins on ribosomes. This process uses transfer RNA (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal RNA (rRNA) links amino acids together to form proteins. Lastly, RNA most commonly exists as a single stranded molecule composed of a phosphate-ribose sugar backbone and the nitrogenous bases adenine, guanine, cytosine and uracil (U). When DNA is transcribed into an RNA transcript during DNA transcription, guanine pairs with cytosine (G-C) and adenine pairs with uracil (A-U). 3 Note that:  Messenger RNA (mRNA) is the RNA transcript or RNA copy of the DNA message produced during DNA transcription. mRNA is translated to form proteins. It carries genetic sequence information between DNA and ribosomes, directing protein synthesis.  Transfer RNA (tRNA) has a three dimensional shape and is necessary for the translation of mRNA in protein synthesis. It serves as the carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA  Ribosomal RNA (rRNA) is a component of ribosomes, catalyzes peptide bond formation and is also involved in protein synthesis.  MicroRNAs (miRNAs) are small RNAs that help to regulate gene expression. Artificial nucleic acid Artificial nucleic acid analogues have been designed and synthesized by chemists, and include peptide nucleic acid, morpholino- and locked nucleic acid, glycol nucleic acid, and threose nucleic acid. Each of these is distinguished from naturally occurring DNA or RNA by changes to the backbone of the molecules. Biosynthesis and degradation The ribose phosphate portion of both purine and pyrimidine nucleotides is synthesized from glucose via the pentose phosphate pathway. The six-atom pyrimidine ring is synthesized first and subsequently attached to the ribose phosphate. The two rings in purines are synthesized while attached to the ribose phosphate during the assembly of adenine or guanine nucleosides. In both cases the end product is a nucleotide carrying a phosphate attached to the 5′ carbon on the sugar. Finally, a specialized enzyme called a kinase adds two phosphate groups using adenosine triphosphate (ATP) as the phosphate donor to form ribonucleoside triphosphate, the immediate precursor of RNA. For DNA, the 2′-hydroxyl group is removed from the ribonucleoside diphosphate to give deoxyribonucleoside diphosphate. An additional phosphate group from ATP is then added by another kinase to form a deoxyribonucleoside triphosphate, the immediate precursor of DNA. During normal cell metabolism, RNA is constantly being made and broken down. The purine (in the form of the corresponding nucleotide) and pyrimidine (as the nucleoside) residues are reused by other pathways to make more genetic material. Nucleotides: building blocks of nucleic acids Nucleic acids are polynucleotides—that is, long chainlike molecules composed of a series of nearly identical building blocks called nucleotides. Nucleotides are joined to one another by covalent bonds between the phosphate of one and the sugar of another, and linked together to form polynucleotide chains. Each nucleotide consists of a nitrogen-containing aromatic base attached to a pentose (five-carbon) sugar, which is in turn attached to a phosphate group. Without an attached phosphate group, the sugar attached to one of the bases is known as a nucleoside. The phosphate group connects successive sugar residues by bridging the 5′- hydroxyl group on one sugar to the 3′-hydroxyl group of the next sugar in the chain. These linkages are called phosphodiester linkages (bonds). Phosphodiester linkages form the sugar- phosphate backbone of both DNA and RNA. Similar to what happens 4 with protein and carbohydrate monomers, nucleotides are linked together through dehydration synthesis. In nucleic acid dehydration synthesis, nitrogenous bases are joined together and a water molecule is lost in the process. Non-standard nucleosides are also found in both RNA and DNA and usually arise from modification of the standard nucleosides within the DNA molecule or the primary (initial) RNA transcript. Transfer RNA (tRNA) molecules contain a particularly large number of modified nucleosides. Comparison chart The chemical structure of RNA is very similar to that of DNA, but differ in these ways: DNA RNA Stands for: DeoxyriboNucleicAcid RiboNucleicAcid A single-stranded chain of alternating A nucleic acid that contains the genetic phosphate and ribose units with the instructions used in the development and bases Adenine, Guanine, Cytosine, and functioning of all modern living Definition: uracil bonded to the ribose. RNA organisms(scientists believe that RNA molecules are involved in protein may have been the main genetic material synthesis and sometimes in the in primitive life forms). transmission of genetic information. Transfer the genetic code needed for the Medium of long-term storage and Job/Role: creation of proteins from the nucleus to transmission of genetic information the ribosome. The helix geometry of DNA is of B- The helix geometry of RNA is of A- Form. DNA is completely protected by Form. RNA strands are continually Unique the body, i.e., the body destroys enzymes made, broken down and reused. RNA is Features: that cleave DNA. DNA can be damaged more resistant to damage by Ultra- by exposure to Ultra-violet rays violet rays. A single-stranded molecule in most of Predominant Double- stranded molecule with a long its biological roles and has a shorter Structure: chain of nucleotides chain of nucleotides Deoxyribose sugar; phosphate backbone; Ribose sugar; phosphate backbone. Bases & Four bases: adenine, guanine, cytosine Four bases: adenine, guanine, cytosine, Sugars: and thymine and uracil Pairing of A-T(Adenine-Thymine), G-C(Guanine- A-U(Adenine-Uracil), G-C(Guanine- Bases: Cytosine) Cytosine) Deoxyribose sugar in DNA is less Ribose sugar is more reactive because reactive because of C-H bonds. Stable in of C-OH (hydroxyl) bonds. Not stable Stability: alkaline conditions. DNA has smaller in alkaline conditions. RNA has larger grooves, which makes it harder for grooves, which makes it easier to be enzymes to "attack" DNA. attacked by enzymes. RNA is synthesized from DNA when Propagation: DNA is self-replicating. needed. The complementary base to adenine is not thymine, as it is in DNA, but rather uracil, which is an unmethylated form of thymine 5 Summary: Nucleic Acids  Nucleic acids are macromolecules that store genetic information and enable protein production.  Nucleic acids include DNA and RNA. These molecules are composed of long strands of nucleotides.  Nucleotides are composed of a nitrogenous base, a five-carbon sugar, and a phosphate group.  DNA is composed of a phosphate-deoxyribose sugar backbone and the nitrogenous bases adenine (A), guanine (G), cytosine (C), and thymine (T).  RNA has ribose sugar and the nitrogenous bases A, G, C, and uracil (U). Other Macromolecules  Biological Polymers: These are macromolecules formed from the joining together of small organic molecules.  Carbohydrates: Carbohydrates include saccharides or sugars and their derivatives.  Proteins: These macromolecules are formed from amino acid monomers.  Lipids: Lipids are organic compounds that include fats, phospholipids, steroids, and waxes References 1. www. en.m. Wikipedia.org>wiki>nucleic acids 2. www. Britannica.com /nucleic acid chemistry. Nucleic acid, Definition, Function, Structures & Types 3. Natural Products Chemistry: Sources, Separations and Structures by Raymond Cooper and George Nicola CRC Press Taylor and Francis Group Boca, Raton London and New York 4. Bioactive Natural Products: Detection, Isolation, and Structural Determination 2nd Edition Edited by Steven M. Colegate and Russel J. Molyneux CRC Press Taylor and Francis Group Boca Raton, London and New York 5. Organic Chemistry Vol 1 and 2 by I.L. Finar 6th Edition 6. Organic Chemistry by Morrison and Boyd 7th Edition 7. National Center for Biotechnology Information (NCBI, https://www.ncbi.nlm.nih.gov) 6 Tutorial Questions 1. What are Nucleic acids? 2. What are the two main events in the life of a cell? 3. How many nucleic acids do we have? Differentiate between them 4. What are the nucleic acid parts? 5. Mention the nucleic acid parts? 6. Draw and name the structure of sugar in nucleic acid 7. Draw and name the structure of nitrogen bases in nucleic acids 8. Draw and name the structure of heterocyclic amines in nucleic acids 9. Briefly explain biosynthesis of nucleic acids. 10. What are phosphodiester linkages in nucleic acid synthesis? 11. List and explain the four types of RNA 12. What are Non-standard nucleosides? 22/03/2021 7