Nucleotides and Nucleosides Overview

Nucleotides

• Nucleotides are essential molecules with diverse roles in living organisms.
• They serve as building blocks for nucleic acids like DNA and RNA, responsible for storing and transferring genetic information.
• They play a major role in energy storage and release through molecules like ATP and ADP.
• Act as signaling molecules mediating the cell's response to external stimuli.
• Their structure consists of three primary components: a nitrogenous base, a five-carbon sugar, and a phosphate group.
• The bases present in nucleotides are classified as purines (adenine and guanine) or pyrimidines (cytosine, thymine, and uracil).
• Purines are larger, containing two fused rings, while pyrimidines have a single six-membered ring.
• The sugar component can be ribose, found in RNA, or deoxyribose, present in DNA.
• The phosphate group attached to the sugar forms a nucleoside.

Nucleosides

• Nucleosides are formed by attaching a nitrogenous base to a sugar (ribose or deoxyribose) through a glycosidic bond.
• The sugar molecule adopts different conformations, known as sugar puckering, affecting the overall structure of the nucleoside.
• Nucleotides are formed when a phosphate group is attached to the 5'-hydroxyl group of the sugar in a nucleoside.
• Phosphate groups are ionized at physiological pH, giving nucleotides an acidic character.

Nucleic acids

• Nucleic acids are polymers of nucleotides linked through phosphodiester bonds.
• The linkage is between the 5'-phosphate group of one nucleotide and the 3'-hydroxyl group of the next nucleotide.
• The sequence of nucleotides in a nucleic acid chain is read from the 5' end to the 3' end.
• DNA is more stable than RNA due to the presence of deoxyribose, which lacks the 2'-hydroxyl group that can react with the phosphate group in RNA.
• The structure of DNA is a double helix, consisting of two antiparallel strands held together by hydrogen bonds between the bases.
• The bases pair specifically: adenine (A) with thymine (T) and guanine (G) with cytosine (C).
• The double helix of DNA can adopt different conformations, including the B form (the most common form), A form (found in dehydrated DNA), and Z form (found in sequences with alternating purines and pyrimidines).

RNA structures

• RNA is typically single-stranded but can fold into complex structures depending on its sequence.
• Messenger RNA (mRNA) carries the genetic code for protein synthesis.
• Transfer RNA (tRNA) acts as an adapter molecule, bringing the correct amino acids to the ribosome during protein synthesis.
• Ribosomal RNA (rRNA) forms part of the ribosome, the site of protein synthesis.
• RNA is able to form base pairs that are not Watson-Crick pairs, like G=U pairs, contributing to its complex secondary structure.
• RNA is more susceptible to alkaline hydrolysis than DNA due to the presence of the 2'-hydroxyl group in ribose.

DNA replication

• DNA replication is the process by which a DNA molecule is copied to produce two identical DNA molecules.
• The process involves the unwinding of the double helix, separating the two strands, and using each strand as a template to synthesize a new complementary strand.
• DNA replication is semi-conservative, meaning that each new DNA molecule contains one original strand and one newly synthesized strand.

DNA damage

• DNA can be damaged by various factors, including exposure to ultraviolet radiation, ionizing radiation, and chemical agents like alkylating agents.
• Alkylating agents add alkyl groups to DNA bases, disrupting base pairing and leading to mutations.
• DNA methylation is a natural process that can play a role in gene expression, but excessive methylation can lead to mutations and cancer.
• Cells have repair mechanisms to correct some types of DNA damage, but some damage can escape repair and contribute to mutations.

Anticancer drugs

• Alkylating agents are used as antineoplastic drugs to damage the DNA of cancer cells.
• Drugs like doxorubicin, an intercalating agent, can inhibit DNA transcription by binding to the DNA helix.
• Radiation therapy can also damage DNA, leading to cell death.

Other nucleotide functions

• Besides their roles in nucleic acids and energy metabolism, nucleotides have other functions:

• They can act as signaling molecules, like cyclic AMP (cAMP), involved in various cellular processes.

• They can be used in the biosynthesis of other molecules, like NADH and FADH2, involved in electron transport chains.

• They are components of coenzymes, essential for enzyme activity.

• They can be used to synthesize important biological molecules like glycoproteins and glycolipids.### Nucleotides and Their Function

• Nucleotides are essential building blocks of DNA and RNA.

• Nucleosides consist of a nitrogenous base linked to a sugar.

• Nucleotides are formed when a phosphate group is added to a nucleoside.

• Nitrogenous bases found in nucleosides and nucleotides include:

  • Adenine (A): Purine base; two-ring structure
  • Guanine (G): Purine base; two-ring structure
  • Cytosine (C): Pyrimidine base; single-ring structure
  • Thymine (T): Pyrimidine base; single-ring structure, found in DNA
  • Uracil (U): Pyrimidine base; single-ring structure, found in RNA

Nucleic Acids: DNA and RNA

• DNA (Deoxyribonucleic acid) is a double helix structure, carrying the genetic code, composed of two antiparallel strands.
• RNA (Ribonucleic acid) is single-stranded, playing critical roles in protein synthesis.
• Main differences between DNA and RNA:
  • Sugar: DNA contains deoxyribose, while RNA contains ribose.
  • Base: DNA contains thymine, while RNA contains uracil.
  • Structure: DNA forms a double helix, while RNA is single-stranded.

DNA Structure and Forms

• A, B, and Z forms of DNA:
  • A-DNA: Right-handed helix, wider and shorter than B-DNA.
  • B-DNA: Right-handed helix, the most common form.
  • Z-DNA: Left-handed helix, often found in sequences rich in GC pairs.
• Unusual DNA structures:
  • Hairpins: Stem-loop structures created when the two ends of a single strand fold back on themselves.
  • Cruciforms: Structures formed by base pairing between two segments of the same strand.

RNA Secondary Structures

• RNA secondary structures:
  • Stem-loop structures: Hairpin loops formed by base pairing between two segments within the same strand.

DNA Denaturation and Renaturation

• DNA denaturation: Breaking the hydrogen bonds between complementary base pairs, resulting in single-stranded DNA.
• DNA renaturation: Reannealing of two complementary single strands of DNA into a double helix.
• Melting temperature (Tm): The temperature at which 50% of the DNA molecules are denatured.

Nucleotide Reactions and Damage

• Non-enzymatic reactions: Spontaneous chemical reactions affecting DNA, such as depurination and deamination leading to base mutations.
• UV radiation damage: Can cause thymine dimers, interfering with normal DNA replication and leading to diseases like xeroderma pigmentosum.

Other Functions of Nucleotides

• Redox coenzymes:
  • NAD+ (Nicotinamide adenine dinucleotide): Important for energy production, electron transfer, and metabolism.
  • FAD (Flavin adenine dinucleotide): Plays a role in various metabolic reactions like respiration.
• Regulatory nucleotides:
  • cAMP (Cyclic adenosine monophosphate): A second messenger involved in signal transduction pathways.
  • cGMP (Cyclic guanosine monophosphate): Acts as a signaling molecule in different cellular processes.