Nucleotides Final PDF

BAHS 233 GENES IN HEALTH AND DISEASE  Goals Identify the basic structure of nucleotides and nucleosides Identify Nucleotide derivatives and analogues Familiar with the different biological roles of nucleotides  Content Structure of Nucleotides Naming o...

BAHS 233 GENES IN HEALTH AND DISEASE  Goals Identify the basic structure of nucleotides and nucleosides Identify Nucleotide derivatives and analogues Familiar with the different biological roles of nucleotides  Content Structure of Nucleotides Naming of Nucleotides Nucleotide Derivatives and Functions Use Nucleotide Analogues as Drugs Biomedical Functions of Nucleotides  In Eukaryotes Wilhelmina Annie Mensah 09/29/2024 4 Dept of Biochemistry, UGMS. UG  A nucleotide is the basic building block of nucleic acids (RNA and DNA). A nucleotide consists of a sugar molecule (either ribose in RNA or deoxyribose in DNA) attached to a phosphate group and a nitrogen-containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). Nucleotide and Nucleoside Nucleoside = Sugar + Base Base Sugar Nucleotide = Nucleoside + Phosphate Nucleoside Phosphate Base Sugar  Composition Nucleotide of + = Nucleoside Phosphate Nucleotides Ester Bond Glycosidic Bond Glycosidic Bond is a bond between a sugar and another group Ester Bond is C-O-R and the oxygen is bounded to something else Composition of Nucleotides Sugar Bases Phosphate  Sugars Pentoses (5-C sugars or carbohydrate) Numbering of sugars is “primed” Sugars(two types Ribose : forming Ribonucelotides Oxygen missing Deoxyribose: forming Deoxynucelotides (d-Nucleotides)  Bases(two types) fused five- and six-membered rings six membered rings Purines -N 9 forms glycosidic bond with the sugar Pyrimidines – N 1 forms glycosidic bond with Bases( Sub-types) Adenine A Guanine G Thymine T Uracil U Cytosine C Pyrimidine Base Structures Purine Base Structures  Bases Occurrence D-nucloetides Ribonucleotides only only Ribonucleotides & D-  Phosphate Groups Phosphates can be bonded to either C5 or C3 They are linked by an Ester bond Ester Bond Mono, Di, Tri phosphate Groups Nucleotide 5’-Monophosphate Nucleotide 5’- Diphosphate Nucleotide 5’- Triphosphate Naming Conventions of Nucleosides Purine nucleosides end in “-sine” – Ribonucleoside Deoxynucleoside Adenosine Deoxyadenosine Guanosine Deoxyguanosine Pyrimidine nucleosides end in “-dine” – Ribonucleoside Deoxynucleoside Deoxythymidine Cytidine Deoxycytidine Naming Conventions of Nucleotides Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate” Ribonucleotides Purines Adenosine monophosphate(AMP), ADP, ATP Guanosine monophosphate(GMP), Pyrimindines GDP, GTP Cytidine Monophosphate, CDP, CTP Uridine Monophosphate, UDP, UTP Naming Conventions of Nucleotides Deoxynucleotides Purines Deoxyadenosine monophosphate (d- AMP), d-ADP, d-ATP d- Guanosine Monophosphate, d-GDP, d-GTP Pyrimindines d- Cytidine Monophosphate, d-CDP, d- CTP d- thymidine Monophosphate, d-TDP, Phosphodiester Bond (linkages) ester bond Phosphodiester bond ester bond Nucleotides are joined together by Nucleic Acids : Polymers of nucleotides Nucleic acid with deoxy ribose sugars--- Deoxyribonucleic acid (DNA) Nucleic acid with Contains ribose sugar---Ribonucleic acid(RNA) Voet, Voet & Pratt 2013 Fig 3.3a,b Deoxyribonucleic acid (DNA)  Deoxyribonucleic acid (DNA) They are held in helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH The stability of the dsDNA form depends not only on the GC- content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable).  Alternative DNA structures DNA exists in many possible conformations that include A- DNA B-DNA, and Z-DNA forms The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling and chemical modifications of the bases.  Alternative DNA structures 1.A-DNA A-DNA is right-handed DNA. It has a double helix structure. The A form of this DNA type is mainly formed because it can protect the DNA while there are any occurrences of extreme conditions B-DNA: B-type DNA is considered the most common form of DNA conformation. It consists of a right-handed helix structure. Moreover, under normal psychological conditions, it is very common to see that much DNA possesses a B-type conformation. 3.Z-DNA: This DNA type is left-handed DNA. Here, a double helix is present, with the wind in a zigzag pattern to the left. Multiple reports claim that the Z- type DNA was found during the start of the gene. Therefore, one can believe that it might have some Alternative DNA structures differences  Telomeres They are specialized regions of DNA found at the ends linear chromosomes The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.[ These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.  Hachimoji DNA Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA.  Hachimoji DNA Hachimoji DNA generally helps in research and DNA manipulation to develop clean diagnostics for human diseases in DNA digital data storage DNA barcoding and to make proteins with unusual amino acids Memory Check Nucleoside Derivatives Adenosine derivatives Guanosine derivative Cytidine derivatives Uridine derivatives  Common Adenosine Adenosine Triphosphate Derivatives (ATP) 3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP) Flavin Adenine Dinucleotide (FAD & FMN) Nicotinaminde Adenine Dinucleotide (NAD+ & NADP) S-adenosylmethionine (SAM) ATP Structure Adenosine Derivatives Adenosine Triphosphate (ATP), FUNCTIONS 1. Energy storage and transfer 2. Release of the third phosphate to produce adenosine diphosphate, or ADP releases energy for cell activity Cyclic AMP Structure Adenosine Derivatives Cyclic AMP or 3'-5'-cyclic adenosine monophosphate, FUNCTIONS 1. Second messenger in signal transduction 2.Regulate metabolism e.g. glycogen breakdown, lipids breakdown etc  Flavin Adenine Dinucleotide (FAD(H2) & FMN(H2) Structure Flavin + H2 Flavin FMN(H2) or FAD(H2) Mononucloetide Riboflavin (FMN) (Vit B 2) sugar FAD phosphate Coenzyme functioning as carrier of hydrogen and electrons in some  Dinucleotide NAD (H)+ and NADP(H)+ Structures +H NADPH NAD NADP Coenzyme functioning as carrier of hydrogen and Coenzyme A Structure Coenzyme serving as acyl group – R(CO) carrier in certain enzymatic reactions S- adenosylmethionine Structure Methyl (CH3) donor in methylation reactions Common Adenosine Adenosine Triphosphate Derivatives (ATP) 3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP) Flavin Adenine Dinucleotide (FAD & FMN) Nicotinaminde Adenine Dinucleotide (NAD+ & NADP) S-adenosylmethionine (SAM) Guanosine Derivative Guanosine Triphosphate (GTP), FUNCTIONS 1. Energy store 2.Energy source for Protein synthesis and Gluconeogenesis 3. Energy source during elongation stage of translation Thymidine Derivatives Ribothymindine Plays a role thermal stability of transfer RNA  Uracil Derivatives UDP-glucose-,glucose donor in glycogen synthesis. UDP-sugar derivatives-----glu, gal, fruc --- used as sugar donors, used in glycoproteins and glycolipids synthesis UDP glucoronate ---- glucuronic acid donor  Cytidine Derivatives CMP-N acetylneuraminic acid (CMP- NANA) required for the biosynthesis of glycoproteins CDP-choline- required for the biosynthesis of sphingolipids (component of cell membrane of brain and nervious tissues). sphingosine CTP- required for the biosynthesis of phosphoglycerides (component of cell membrane) Synthetic Analogues of Nucleotides An analogue is an organic chemical compound related to another by substitution of atoms with other groups Nucleotide analogues are prepared by altering the base ring or sugar moiety. Chemically synthesized nucleotides used as drugs in clinical therapy  Synthetic Analogues of Nucleotides: Anti-tumour agents used in chemotherapy Interfere with the synthesis of DNA and thereby preferentially kill rapidly dividing cells such as tumor cells. 6- mercaptopurine) 5-fluorouracil  Synthetic Analogues of Nucleotides: Anti-tumour agents used in chemotherapy  Synthetic Analogues of Nucleotides: Anti-Viral agents Used to interfere with the replication of viruses by terminating DNA synthesis AZT (azidothymidine or zidovudine) - HIV Lamivudine ----- Hepatitis B  Synthetic Analogues of Nucleotides: Treatment of Gout Caused by accumulation of uric acid Allopurinol is a structural analogue of hypoxanthine is used treat gout The drug is an inhibitor of the enzyme xanthine oxidase which converts hypoxanthine to uric acid Biomedical importance of nucleotides Storage and transfer of energy (ATP and GTP ) Precursors of nucleic acids, DNA & RNA Storage and transfer of genetic information (DNA & RNA) Components of important co- enzymes ( like NAD+ and FAD, Co-enzyme A) Biomedical importance of nucleotides Metabolic rgulators such as cAMP CTP and UTP are both used in the production of biomolecules Synthetic analogues used in medicine e.g. 5-fluorouracil Memory Check  Memory Check D-nucloetides Ribonucleotides only only Ribonucleotides & D-  Memory Check Adenosine Triphosphate (ATP) 3'-5'-Cyclic Adenosine Monophosphate, “(cAMP or cyclic AMP) Flavin Adenine Dinucleotide (FAD & FMN) Nicotinaminde Adenine Dinucleotide (NAD+ & NADP) S-adenosylmethionine (SAM) Memory Check Memory Check Memory Check Memory Check Memory Check Memory Check  Memory Check Guanosine Triphosphate (GTP), UDP-sugar derivatives; glu, gal, fruc CMP-N acetylneuraminic acid (NANA) Cytidine Triphosphate (CTP) Memory Check Memory Check Memory Check Memory check  Content Structure of Nucleotides Naming of Nucleotides Nucleotide Derivatives and Functions Use Nucleotide Analogues as Drugs Biomedical Functions of Nucleotides Nucleotide Chemistry BAHS 233 Thank you Minor Pyrimidine nucleosides Minor Purine Nucleosides