Nucleotide Structure and Functions

Nucleotide Structure

• Nucleotides are composed of three parts: a phosphate group, a pentose sugar (ribose or deoxyribose), and a nitrogenous base.
• The nitrogenous bases are purines (adenine and guanine) or pyrimidines (cytosine, thymine, or uracil).
• Purines are larger, with a double ring structure.
• Pyrimidines are smaller, with a single ring structure.
• Thymine is found in DNA, while uracil is found in RNA.

Nitrogenous Bases

• Purines include adenine (A) and guanine (G), both present in both DNA and RNA.
• Pyrimidines include cytosine (C), thymine (T), and uracil (U). Cytosine is in both DNA and RNA. Thymine is specific to DNA, and uracil is specific to RNA.

Sugars

• Ribose is the sugar found in RNA.
• Deoxyribose is the sugar found in DNA.
• The difference is the presence or absence of an oxygen atom on the 2' carbon of the sugar.

Phosphate Groups

• Nucleotides can have one, two, or three phosphate groups attached to the sugar.
• Monophosphate (e.g., AMP), diphosphate (e.g., ADP), and triphosphate (e.g., ATP) are examples of nucleotides with varying numbers of phosphate groups.

Nucleotide vs. Nucleoside

• A nucleoside contains a nitrogenous base and a pentose sugar.
• A nucleotide consists of a nucleoside plus one or more phosphate groups.

Nucleotides and Nucleosides

• Nucleotides are the building blocks of nucleic acids (DNA and RNA).
• Nucleosides are the bases connected to sugars.
• Nucleobases are the nitrogenous bases.

Glycosidic Bond

• The bond between the nitrogenous base and the sugar is a β-N-glycosidic bond, which links the base to C1' of the pentose sugar.
• N-glycosidic bonds are formed between N1 of pyrimidines and C1 of pentose sugars or, for purines, N9 of the purine with C1 of the pentose sugar.

Bonds in Nucleotides

• N-glycosidic bond, connecting the base to the sugar.
• Ester bond, connecting the phosphate group to the sugar.
• Anhydride bond, connecting the phosphate groups.

Naming Conventions

• Nucleotide names are formed by combining the nucleoside name with "mono-," "di-," or "triphosphate." This describes the number of phosphate groups. For example, adenosine monophosphate (AMP).

Deoxynucleotides

• Deoxynucleotides are similar to nucleotides but contain deoxyribose sugar instead of ribose. This applies to purines and pyrimidines.

Ribonucleotides

• Contain a ribose sugar instead of a deoxyribose sugar, which applies to purines and pyrimidines.

Modified Nucleotides

• Some DNA and RNA nucleotides can be modified.
• These modifications can affect the function of the nucleic acid. Some minor modified bases act to protect or regulate genetic information.

Degradation of Nucleic Acids

• Nucleic acids are degraded to their components in the small intestine.

UV Absorption

• Nucleotides absorb UV light at around 260nm. This can be used to quantify DNA and RNA.

Nucleoside Derivatives

• Adenosine, guanosine, cytidine, and uridine derivatives exist.
• These modified nucleotides often play significant biological roles.

Common Adenosine Derivatives

• ATP, cyclic AMP (cAMP), FAD & FMN, NAD+ & NADP+, SAM are common adenosine derivatives.

ATP-ADP Cycle

• ATP is a vital energy currency in cells.
• The ATP-ADP cycle describes how ATP is converted to ADP and back to ATP, releasing or storing energy.

Donor of Phosphate Group

• ATP is a key donor of phosphate groups in phosphorylation reactions. This is a critical aspect of energy transfer and metabolic regulation.

Cyclic AMP (cAMP)

• A secondary messenger molecule in signal transduction pathways.
• cAMP can regulate metabolism by stimulating or inhibiting various processes.

Flavin Adenine Dinucleotide (FAD) & Flavin Mononucleotide (FMN)

• Coenzymes that act as electron carriers, participating in redox reactions.
• They play important roles in many metabolic pathways

Nicotinamide Adenine Dinucleotide (NAD)/NADP

• Coenzymes functioning as electron carriers.
• They are essential participants in redox reactions, particularly in cellular respiration and biosynthesis.

Coenzyme A (CoA)

• A coenzyme that carries acetyl or acyl groups.
• Critical participant in many metabolic processes like the citric acid cycle and fatty acid oxidation.

S-Adenosylmethionine (SAM)

• A methyl group donor in methylation reactions.
• Involved in many cellular processes such as DNA and protein methylation.

Guanosine Derivatives

• GTP is a crucial energy source in various metabolic processes.
• cGMP is a second messenger in cellular signaling.

Thymidine Derivatives

• Ribothymidine plays a role in the thermal stability of transfer RNA

Uracil Derivatives

• UDP-glucose is a glucose donor in glycogen synthesis.
• Other UDP-sugar derivatives are used in glycoprotein and glycolipid synthesis.

Cytidine Derivatives

• CMP-N-acetylneuraminic acid is essential for glycoprotein biosynthesis.
• CDP-choline is vital for sphingolipid biosynthesis.
• CTP is involved in the biosynthesis of phospholipids.

Synthetic Analogues of Nucleotides

• Compounds similar to natural nucleotides are synthetic analogues.
• Used in medicine (antiviral and anticancer drugs).
• Crucial tools in molecular biology.

Anti-tumour agents

• Inhibit specific enzymes essential for nucleic acid synthesis.
• Incorperate into nucleic acids, disrupting base pairing.
• Preferential targeting of rapidly dividing cells. Includes drugs like 5-fluorouracil, 5-iodo-deoxyuridine, and 6-mercaptopurine targeting thymine, thymidine, and purine analogues, respectively.

Anti-viral agents

• Nucleoside analogues to interfere with viral DNA replication, such as lamivudine, and azidothymidine.

Use in Molecular Biology

• Nucleic acid analogues are valuable tools for detecting sequences.
• Used in studies of RNA hydrolysis mechanisms.
• Can act as enzyme inhibitors to investigate metabolic pathways and the origin of life mechanisms.

Allopurinol

• Inhibits the enzyme xanthine oxidase, which is crucial in purine metabolism.
• Used to treat hyperuricemia and gout (caused by high uric acid levels).