Nucleotide - PDF

# Nucleotide A nucleotide consists of three components: - Phosphate - Pentose Sugar - Base ## Base The base can be either a purine or pyrimidine. ### Purines - Adenine (A) - Guanine (G) ### Pyrimidines - Cytosine (C) - Thymine (T) - Uracil (U) ## Nitrogenous Bases ### Purines - Adenine (D...

# Nucleotide A nucleotide consists of three components: - Phosphate - Pentose Sugar - Base ## Base The base can be either a purine or pyrimidine. ### Purines - Adenine (A) - Guanine (G) ### Pyrimidines - Cytosine (C) - Thymine (T) - Uracil (U) ## Nitrogenous Bases ### Purines - Adenine (DNA, RNA) - Guanine (DNA, RNA) ### Pyrimidines - Cytosine (DNA, RNA) - Thymine (DNA) - Uracil (RNA) ## Pyrimidines The image depicts the chemical structures of three pyrimidines: - Thymine - Cytosine - Uracil ## Sugars ### Ribose - $HOCH_2O$ ### Deoxyribose - $HOCH_2O$ ## Phosphate Groups - **Monophosphate** - e.g. AMP → Adenosine monophosphate - **Diphosphate** - e.g. ADP → Adenosine diphosphate - **Triphosphate** - e.g. ATP → Adenosine triphosphate ## Nucleotide & Nucleoside - **Nucleoside:** Base + Sugar - **Nucleotide:** Base + Sugar + Phosphate ## Nucleotides and Nucleosides - **Nucleotide** - Nitrogeneous base - Pentose - Phosphate - **Nucleoside** - Nitrogeneous base - Pentose - **Nucleobase** - Nitrogeneous base ## Glycosidic bond - Pyrimidine N1 forms Glycosidic bond - Purine N9 forms Glycosidic bond ## Nucleotides - N-glycosidic bond - ester bond - anhydride bond ## 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), GDP, GTP #### Pyrimindines - Cytidine Monophosphate, CDP, CTP - Uridine Monophosphate, UDP, UTP ### 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, d-TPP ## Nucleotides: Ribonucleotides The image depicts the four ribonucleotides: - Adenylate (Adenosine 5'-monophosphate): A, AMP - Guanylate (Guanosine 5'-monophosphate): G, GMP - Uridylate (Uridine 5'-monophosphate): U, UMP - Cytidylate (Cytidine 5'-monophosphate): C, CMP ## Modified Nucleotides Altered or unusual bases in DNA molecules often have roles in regulating or protecting the genetic information. - Inosine - Pseudouridine - 7-Methylguanosine - 4-Thiouridine ## Degradation of Nucleic Acid - Nucleoprotein in the stomach is degraded by gastric acid and pepsin. - Nucleic acid and protein are then degraded in the small intestine by endonucleases, RNase and DNase. - Nucleotide is further degraded by nucleotidase into phosphate and nucleoside. - Nucleoside can be further degraded by a nucleotidase into a base and ribose. ## Nucleotides absorb UV light Nucleotides absorb UV light around 260nm, making this wavelength convenient for measuring DNA or RNA. ## Nucleoside Derivatives - Adenosine derivatives - Guanosine derivative - Cytidine derivatives - Uridine derivatives ## Common Adenosine Derivatives - Adenosine Triphosphate-ATP - 3'-5'-Cyclic Adenosine Monophosphate: c AMP or cyclic AMP - Flavin Adenine Dinucleotide: FAD & FMN - Nicotinaminde Adenine Dinucleotide: NAD+ & NADP - S-adenosylmethionine-SAM ## ATP-ADP Cycle - **ATP** is used for motion, active transport, biosynthesis, and signal amplification. - **ADP** is produced by oxidation of fuel molecules or photosynthesis. ## Donor Of Phosphate Group In Phosphorylation Reactions - The image depicts the transfer of a phosphate group from ATP to glucose. - This reaction results in the formation of glucose-6-phosphate. ## Cyclic AMP Structure - **ATP** is converted to cyclic AMP by adenylyl cyclase. - Pyrophosphate is a by-product of this reaction. ## c AMP (adenosine 3',5'-monophosphate) - c AMP is a secondary messenger in signal transduction. - c AMP regulates metabolism, such as glycogen breakdown, lipid breakdown. ## Flavin Adenine Dinucleotide FAD(H2) or Flavin Mononucleotide FMN(H2) - Coenzyme functioning as carrier of hydrogen and electrons in some redox reactions ## Nicotinamide Adenine Dinucleotide: NAD(H)* and NADP(H)* - Coenzyme functioning as carrier of hydrogen and electrons in some redox reactions ## Coenzyme A Structure - **Coenzyme A** serves as an acyl group or acetyl group carrier in certain enzymatic reactions. ## S-adenosylmethionine Structure - **Methionine** is converted to S-adenosylmethionine by methionine adenosyltransferase. - S-adenosylmethionine is a methyl (CH3) donor in methylation reactions. ## Guanosine Derivative - **Guanosine Triphosphate (GTP):** - Energy source for metabolism - cGMP is a second messenger in signal transduction. - Energy source for protein synthesis and gluconeogenesis. ## Thymidine Derivatives - **Ribothymidine** plays a role in the thermal stability of transfer RNA. ## Uracil Derivatives - **UDP-glucose** acts as a glucose donor in glycogen synthesis. - **UDP-sugar derivatives** such as glu, gal, and fruc are used as sugar donors. They are involved in glycoproteins and glycolipids synthesis. - **UDP glucoronate** acts as a glucuronic acid donor. ## Cytidine Derivatives - **CMP-N acetylneuraminic acid (CMP- NANA)** is required for the biosynthesis of glycoproteins. - **CDP-choline** is required for the biosynthesis of sphingolipids. Sphingolipids are components of the cell membrane of brain and nervous tissues. - **CTP** is required for the biosynthesis of phosphoglycerides. Phosphoglycerides are components of the cell membrane. - **CTP** is a source of energy in metabolism. ## Synthetic Analogues of Nucleotides - A compound with a molecular structure closely similar to that of another. - Nucleotide analogues are prepared by altering the base ring or sugar moiety. - They are chemically synthesized and used in clinical therapy. ### Anti-tumor Agents - Inhibit specific enzymes essential for nucleic acid synthesis. - Incorporate into nucleic acids, affecting base pairing for accurate replication. - Preferentially kill rapidly dividing cells such as tumor cells. - 5-fluoro uracil → thymine analog - 5-iodo deoxyuridine → thyminide analog - 6-mercaptopurine → purine analaog ### Anti-Viral Agents - Nucleoside analogues are an important class of antiviral agents used in the therapy of diseases such as HIV infection, hepatitis B virus (HBV), hepatitis C virus (HCV). - They interfere with the replication of viruses by terminating DNA synthesis. - Lamivudine - Hepatitis B - Azidothymidine (AZT) - HIV ## Use in Molecular Biology Nucleic acid analogues are used in molecular biology for several purposes: - As a tool to detect particular sequences - As a tool with resistance to RNA hydrolysis - As a tool for other purposes, such as sequencing - Investigation of the mechanisms used by enzymes, such as an enzyme inhibitor - Investigation of possible scenarios of the origin of life - Investigation of the structural features of nucleic acids - Investigation of the possible alternatives to the natural system in synthetic biology ## Synthetic Analogues of Nucleotides - 4-hydroxypyrazolopyrimidine (Allopurinol → purine analaog) - Allopurinol inhibits de novo purine biosynthesis and xanthine oxidase activity. - It is used for the treatment of hyperuricemia and gout.