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Nucleotides and Nucleic Acids Summary 1. 2. 3. 4. 5. 6. 7. 8. August2010 Introduction to nucleic acids and their biochemical functions Nucleotide structure and nomeclature Modified nitrogenous bases Nucleotide derivatives Nucleotide synthetic analogs Polynucleotides DNA as the genetic material Manipulations of DNA HBC108/2010 UON EGK 2 Introduction to Nucleic acids { The major nucleic acids of the cell are: z Ribonucleic acid (RNA)and Deoxyribonucleic acid (DNA). { DNA is a nucleic acid polymer found in the nucleus { It is the genetic material, the form in which genetic information is stored { Minor DNA is found in the mitochondria and used in the synthesis of mitochondrial proteins August2010 HBC108/2010 UON EGK 3 Introduction to Nucleic acids { RNA is a nucleic acid polymer synthesized from DNA in a process referred to as transcription { The ribosome structure in the cytosol is made up of a type of RNA { Another type of RNA forms a nucleic acid template bearing codes of amino acids which are used for protein synthesis in the ribosomes { A third type of RNA is involved in binding and transfer of amino acids from the cytosol to the ribosomes for protein synthesis August2010 HBC108/2010 UON EGK 4 Other functions 1. 2. 3. August2010 Serving as energy stores in phosphate transfer reactions predominantly carried out by Adenosine Triphosphate (ATP). Forming a portion of several important coenzymes such as NAD+, NADP+, FAD and coenzyme A. Controlling numerous enzymatic reactions through allosteric effects on enzyme activity e.g. Guanosine Triphosphate (GTP) HBC108/2010 UON EGK 5 Functions { Serving as mediators of numerous important cellular processes such as second messengers in signal transduction events. z The predominant second messenger is cyclic-Adenosine Monophosphate (cAMP), a cyclic derivative of AMP formed from ATP z Also cyclic-Guanosine Monophosphate cGMP. { Serving as activated intermediates in numerous biosynthetic reactions. z S-adenosylmethionine (s-AdoMet) involved in methyl transfer reactions in glycogen synthesis August2010 HBC108/2010 UON EGK 6 Introduction to nucleotides { Nucleotides are monomers of major nucleic acids { Consists of z a nitrogen containing base (nitrogenous bases) {Two types of nitrogenous base occur z A phosphate group, z A five carbon sugar (either ribose or deoxyribose) August2010 HBC108/2010 UON EGK 7 { Nucleotides are monomers consisting of { a one or two ring nitrogen containing base. { a phosphate group { a five carbon sugar (either ribose or deoxyribose) Nitrogenous bases { These are functional groups consisting of one or two rings containing both carbon and nitrogen. { These bases are derivatives of the heterocyclic highly basic, nitrogenous compounds: 1. Purines 2. Pyrimidines { August2010 It is the chemical basicity of the nucleotides that has given them the common term "bases." HBC108/2010 UON EGK 9 Structure of a purine and a pyrimidine Pyrimidine Purine August2010 HBC108/2010 UON EGK 10 Nitrogenous bases { There are five different nitrogenous bases, each is denoted by a single letter 1. 2. 3. 4. 5. { The derivatives of purines are z { Adenine and guanine And the derivatives of pyrimidines are z August2010 Adenine (A) Cytosine (C) Guanine (G) Thymine (T) Uracil (U) Thymine, cytosine and uracil HBC108/2010 UON EGK 11 Purines 6 1 1 6 7 3 3 7 9 9 Guanine (G) Adenine (A) August2010 HBC108/2010 UON EGK 12 Pyrimidines 2 2 1 6 Cytosine (C) August2010 1 6 6 1 Thymine (T) HBC108/2010 UON Uracil (U) EGK 13 Nucleosides { Purine and pyrimidine bases in cells occur linked to a carbohydrate { and in this form are termed as nucleosides { Nucleosides are N-glycosides of two types of pentose sugars { Nucleosides are formed by the loss of water from a sugar and a purine or pyrimidine base Nucleosides { The pentose sugars found coupled to nitrogenous bases to form nucleosides are 1. D-ribose 2. 2'-deoxy-D-ribose { The two sugars are linked through a Nglycosidic bond between the anomeric carbon of the sugar and the N9 of a purine or N1 of a pyrimidine. Pentoses found in nucleotides The chemical structure of pentose which contains five carbon atoms, labeled as C1' to C5'. The pentose is called ribose in RNA and deoxyribose in DNA, because the DNA's pentose lacks an oxygen atom at C2'. Structure of nucleosides 1 1 3 9 9 3 1' 1' syn-Adenosine August2010 HBC108/2010 anti-Adenosine UON EGK 17 Structures of purine nucleosides Base Formula Base (X=H) Adenine, A Guanine, G Nucleoside X=ribose or deoxyribose Adenosine, A Guanosine, A Adenosine Guanosine Structures of pyrimidine nucleosides Base Formula Base (X=H) Nucleoside X=ribose or deoxyribose Cytosine, C Cytidine, A Uracil, U Uridine, U Thymine, T Deoxythymidine, T Cytidine Uridine Deoxyribonucleosides Deoxyadenosine H Deoxyguanosine H Deoxycytidine H Thymidine (Deoxythymidine) H Practice { Draw and name the nucleosides derived from the different bases Nucleotides { Nucleosides are found in the cell primarily in their phosphorylated form. { These are termed nucleotides. { Nucleotides are phosphate esters of nucleosides { The most common site of phosphorylation of nucleotides is the OH group attached to the 5'-carbon of the ribose August2010 HBC108/2010 UON EGK 25 Nucleotides { Monophospates can be further phosphorylated to produce di- and tri- phosphates { Thus nucleotides can exist in the mono-, di-, or tri-phosphorylated forms { At physiological pH, the phospates are ionized { The ionization of the phospates means that RNA and DNA bear multiple negative charges (polyelectrolytes) { Thus cations of various kinds, especially Mg++, tend to cluster near the phosphates. August2010 HBC108/2010 UON EGK 26 Structures of purine nucleotides Base Formula Base (X=H) Adenine, A Guanine, G Nucleoside X=ribose or deoxyribose Nucleotide X=ribose phosphate Adenosine, A Adenosine monophosphate AMP Guanosine, A Guanosine monophosphate GMP Adenylate phosphorylations Structures of pyrimidine nucleotidess Base Formula Base (X=H) Cytosine, C Nucleoside X=ribose or deoxyribose Cytidine, A Nucleotide X=ribose phosphate Cytidine monophosphate CMP Uracil, U Uridine, U Uridine monophosphate UMP Thymine, T Thymidine, T Deoxy-thymidine monophosphate TMP Nucleotide nomenclature { Nucleotides are given distinct abbreviations to allow easy identification of their structure and state of phosphorylation. { The monophosphorylated form of adenosine (adenosine-5'monophosphate) is written as, AMP. { The di- and tri-phosphorylated forms are written as, ADP and ATP, respectively. August2010 HBC108/2010 UON EGK 30 Nucleotide- acid anhydride bonds { The use of these abbreviations assumes that the nucleotide is in the 5'-phosphorylated form. { The di- and tri-phosphates of nucleotides are linked by acid anhydride bonds. { Acid anhydride bonds have a high ΔG for hydrolysis imparting upon them a high potential to transfer the phosphates to other molecules. August2010 HBC108/2010 UON EGK 31 Deoxyribonucleotides { The nucleotides found in DNA are unique from those of RNA { The ribose exists in the 2'-deoxy form and the abbreviations of the nucleotides contain a d designation. { The monophosphorylated form of adenosine found in DNA (deoxyadenosine-5'-monophosphate) is written as dAMP. August2010 HBC108/2010 UON EGK 32 Deoxynucleotides { The nucleoside uridine is never found in DNA and thymine is almost exclusively found in DNA. { Thymine is found in tRNAs but not rRNAs nor mRNAs. { There are several less common bases found in DNA and RNA. August2010 HBC108/2010 UON EGK 33 Learning check 1 { Draw the structures and name the di- and tri- nucleotides derived from the five bases { Show the abbreviated name for each August2010 HBC108/2010 UON EGK 34 August2010 HBC108/2010 UON EGK 35