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Bsc Chemistry ____________________________________________________________________________________________________ Subject Chemistry Paper No and Title 16; bioorganic and biophysical chemistry Module No and Title 5; Nucleotides and Polynucleotides Module Tag CHE_P16_M5 Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 2.1 Monomer and the polymer 3. The Nucleotides 3.1 Nitrogenous bases 3.2 Pentoses 3.3 Nucleoside 3.4 Nucleotide 4. Importance of nucleosides and nucleotides in the cell 4.1 Adenosine 4.2 Cyclic nucleotide 4.3 Energy source for the cell 4.4 Building blocks of DNA and RNA 5. Polynucleotides 6. Summary Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ 1. Learning Outcomes After studying this module you shall be able to: Know about nucleotides are monomers that frame the DNA and the RNA. Learn about nucleotides comprise of pentose sugar, nitrogenous bases and phosphate. Understand polynucleotides (DNA or RNA) are elements of heredity. Know about nucleotides provide energy for many cellular processes. 2. Introduction 2.1 Monomers and the Polymer Nucleotides and polynucleotides are biological molecules which play numerous roles inside the cell. Nucleotides (monomer) are the repeating units that form the polynucleotides (polymer). Polynucleotides are of two kinds: DNA or Deoxyribonucleic acid and RNA or Ribonucleic acid. Just like letters in a sentence, the sequence of nucleotides in a polynucleotide carries information. They are the biomolecules that carry genetic information. Nucleotides are composed of nitrogenous bases, a five-carbon sugar and phosphate. DNA is much stable than RNA but both are used to store genetic information by organisms. Few viruses use RNA as genetic material. 3. The Nucleotides 3.1 Nitrogenous Bases Nucleotides are comprised of single-ringed or two-ringed nitrogenous bases. One-ringed nitrogenous base is called the pyrimidine and the two-ringed nitrogenous base is called the purine. Basic structure of purine or pyrimidine is shown in Figure 1. Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Figure 1. The structure of one –ringed pyrimidine (a) and two-ringed purine bases (b). The atoms are conventionally numbered as indicated. Pyrimidines are six-membered aromatic rings containing two N-atoms. Purines’ structure is a combination of pyrimidine ring and a five membered imidazole ring. 3.1.1 The Pyrimidines The pyrimidine bases are of three kinds: Cytosine (C), Uracil (U) and Thymine (T). Cytosine and Thymine are found in DNA while Cytosine and Uracil are found in RNA. Their structures are shown in Figure 2. Figure 2: The structures of three pyrimidine bases: Cytosine, Thymine and Uracil. Thymine is only found in DNA while Uracil is only found in RNA. Cytosine is 2-oxy-4-amino pyrimidine, Uracil is 2-oxy-4-oxy pyrimidine and Thymine is 5-methyl Uracil. 3.1.2 The Purines Two kinds of purine bases exist in nucleotides: Adenine (A) and Guanine (G). Both are found in DNA as well as RNA. Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Figure 3: The structures of two purine bases: Adenine and Guanine. Adenine is 6-amino purine and Guanine is 2-amino-6-oxy purine. Other purines also exist in cell but not as part of polynucleotides. They are Hypoxanthine, Xanthine and Uric acid. Their structures are shown in Figure 4. Figure 4. Structures of other purines that exist in cell. They are Hypoxanthine, Xanthine and Uric acid. 3.1.3 Keto-enol Tautomerism The purines and pyrimidines can undergo keto-enol tautomerism. Thus bases exist in predominant keto or lactam form and rare enol or lactim form. 3.1.4 UV absorption spectra Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Nitrogenous bases because of aromatic ring structure can absorb Ultraviolet light. This characteristic absorption of UV light at 260 nm is useful in quantitative and qualitative analysis of bases, nucleotides and nucleic acids. 3.2 Pentoses Pentoses are the five-carbon sugars present in polynucleotides. RNA contains D-Ribose while DNA contains 2’-deoxy-D-ribose (Figure 5). The hydroxyl group at the 2’-position is not present in DNA, rather a H atom is present there. We shall see in later sections how this minor difference has far-reaching consequences on their properties. Figure 5. The structures of pentoses: (a) D-Ribose and (b) 2’-deoxy D-Ribose 3.3 Nucleoside Nucleosides are formed by joining a sugar to a nitrogenous base via a β-N-glycosidic linkage. If the nitrogenous base is a purine, the nitrogenous base is linked to the sugar via its N-9 atom, while if it’s a pyrimidine, it is linked via its N-1 atom. Nucleoside with purine as base are suffixed with ‘osine’. For example, adenosine and guanosine. While nucleoside with pyrimidine as base are suffixed with ‘idine’. For example, cytidine, uridine, thymidine. If the sugar of the nucleoside is 2-deoxy ribose, the nucleosides are named as deoxyribonucleosides- deoxyadenosine, deoxyguanosine etc. Figure 6 shows the structures of all ribonucleosides and deoxyribonucleosides. Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Figure 6. The structures and nomenclature of ribonucleosides and deoxyribonucleosides. The base hypoxanthine when bonded to a ribose forms the nucleoside inosine. Nucleosides can exist in two conformations: anti and syn; based on the rotation of β-N-glycosidic linkage. For example: Guanosine can exist in anti and syn forms. In syn conformation, the –NH2 substituent lies above the furanose ring while in the anti conformation, it lies away from the furanose ring. 3.4 Nucleotide Nucleotides are nucleoside phosphates. Phosphoric acid can be esterified to sugar –OH group via phosphoester bond. Ribose presents three such –OH groups–2’, 3’ and 5’, while deoxyribose has only two hydroxyl groups–3’ and 5’. Nucleoside 5’ phosphates are predominantly found in the cell. If one phosphate moiety is bonded to the base, it is called nucleoside monophosphate (NMP). Similarly, nucleoside di and triphosphates (NDP and NTP) are found in the cell (Figure 7). Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Figure 7. The structure of Nucleoside 5’-mono-, di- and tri-phosphate. 4. Importance of nucleosides and nucleotides in the cell 4.1 Adenosine Nucleosides serve as precursors to nucleotides. But adenosine apart from serving as a precursor also acts as a local hormone that circulates in the bloodstream and perform functions like: blood vessel dilation, smooth muscle contraction and regulates sleep. 4.2 Cyclic nucleotide Nucleoside monophosphates can form intramolecular phosphoester bond where phosphoric acid moiety can be linked to two hydroxyls of the same ribose moiety thus, leading to formation of cyclic nucleotides. 3’,5’ cyclic AMP (cAMP) and 3’,5’ cyclic GMP (cGMP) are cyclic nucleotides that have important role in cellular signaling. They serve as second messengers. Chemistry PAPER No. : 16, Bioorganic and Biophysical chemistry MODULE No. : 5, Nucleotides and polynucleotides ____________________________________________________________________________________________________ Figure 8. 3’,5’-cyclic AMP (cAMP) 4.3 Energy Source for the cell Nucleoside 5’-phosphates are prime source of chemical energy for the cell. ATP is the energy currency of the cell. GTP participates in protein synthesis while CTP and UTP provide energy for phospolipid and carbohydrate synthesis. 4.4 Building blocks of DNA and RNA DNA and RNA are polymers of nucleotides. Two polynucleotide chains join in antiparallel fashion to frame the structure of DNA, while a single polynucleotide chain forms the RNA. 5. Polynucleotides Nucleic acids are biopolymers of nucleotides linked to each other via a 3’ to 5’ phosphodiester bond. This intermolecular linkage links 3’ hydroxyl of one nucleotide molecule to 5’ hydroxyl of another molecule linking the adjacent nucleotides. If the repeating unit is ribonucleoside monophosphate, it forms the ribonucleic acid or RNA. However, if the repeating unit is deoxyribonucleoside monophosphate, it forms the deoxyribonucleic acid or DNA. One polynucleotide chain makes the RNA, hence it is single stranded. Two polynucleotide chains make the DNA, hence it is double stranded. Polynucleotide chains are represented as shown in Figure 9. Figure 9A illustrates the polynucleotide chain where adjacent nucleotides are linked by phosphodiester linkage. Figure 9B shows the shorthand notation of a phosphodiester bond. The straight line
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