Nucleic Acids and Their Functions

Biomolecules

• Biomolecules are large molecules essential for life
• Types of biomolecules: proteins, carbohydrates, lipids, nucleic acids
• Nucleic acids are polymers comprised of repeating units called nucleotides

Nucleic Acids and Nucleotides

• Nucleic acids store and express genetic information
• There are two types of nucleic acids: DNA and RNA
• Nucleic acids are biopolymers made of monomers called nucleotides
• Nucleotides consist of a sugar, a phosphate group, and a nitrogenous base
• The types of sugars found in nucleotides are ribose and deoxyribose
• Specific nitrogenous bases—adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U)—are fundamental components of DNA and RNA

Functions of DNA and RNA

• DNA stores and transmits biological information
• Genes are segments of DNA specifying protein or RNA production
• Several RNA classes exist (rRNA, tRNA, mRNA):
  • rRNA are ribosome components
  • mRNA translates DNA code to proteins
  • tRNA acts as an adaptor carrying amino acids to ribosomes

Nucleotides

• Nucleotides have various roles in cellular metabolism:
  • Energy currency (e.g., ATP)
  • Involved in cellular communication
  • Structural components of enzymes and cofactors.
• Nucleotides are also constituents of nucleic acids (DNA and RNA)

Nucleotides – Basic Structure

• Each nucleotide comprises a sugar bound to a phosphate group and a nitrogenous base

Nucleotides – Chemical Structure

• Each nucleotide includes a phosphate group, a sugar, and a nitrogenous base

Nucleotides - (1) Sugar Base

•  Nucleotides have two types of sugars – ribose and deoxyribose

  • DNA nucleotides only contain deoxyribose; RNA nucleotides only contain ribose.

•  Numbers on the sugar ring are "primed" to distinguish them from the numbered atoms of the nitrogenous bases

Ribose and Deoxyribose

• Ribose and deoxyribose are five-carbon sugars
• The only difference is that deoxyribose lacks the oxygen atom at the 2nd carbon position, which makes deoxyribose more stable.

Conformation of Ribose

• Ribose has aldehyde and ring forms
• RNA: β-D-ribofuranose ring form
• DNA: β-2'-deoxy-D-ribofuranose exclusively

Nucleotides – (2) Phosphate Group

•  Nucleotides are polar due to highly ionized oxygen atoms in the phosphate groups
• ATP (adenosine triphosphate) is a crucial nucleotide in energy transfer in cells.

Nucleotides – (3) Nitrogenous Bases

• Nitrogenous bases are organic molecules with nitrogen and act as bases in chemical reactions.
• Planar, aromatic, and heterocyclic structures
• Derived from purines (adenine & guanine) or pyrimidines (cytosine, thymine & uracil)

Two Classes of Nitrogen Bases

• Purines (A, G) are double-ring structures
• Pyrimidines (C, T, U) are single-ring structures

Purines and Pyrimidines

• Purines include adenine and guanine.
• Pyrimidines include cytosine, thymine, and uracil.

Nucleoside

• Nucleoside formed by removing the phosphate group from a nucleotide

Structure – Review

• Nucleotides are the building block of nucleic acids

Bonding of the groups to the sugar – (1) Nitrogenous Base

• The nitrogenous base is connected to the sugar via an N-glycosidic bond, which is a covalent bond.
• Purines (A, G) bond at the C1' carbon via the N9 atom
• Pyrimidines (C, T, U) bond at the C1' carbon via the N1 atom

Bonding of the groups to the sugar – (2) Phosphate Group

• The phosphate group is esterified to the 5' carbon of the sugar

To Review at home

• The base, sugar and phosphate are joined covalently in a nucleotide
• The elements of water are removed to form an N-glycosidic bond.
  • A hydroxyl group from the pentose sugar
  • A hydrogen from the nitrogenous base

Nucleotides (Summary)

• Monomers of nucleic acids (DNA, RNA)
• Nucleotides link to create nucleic acids via esterification

Naming Conventions

• Nucleosides end in "-sine" (purines) or "-dine" (pyrimidines)
• Nucleotides add "mono-," "di-," or "triphosphate" to the nucleoside name

Nomenclature of Nucleosides and Nucleotides

• Nucleotides vary by the bases and sugars they contain; their names often reflect this variation.
• These terms are important in biochemistry for naming and describing nucleotides

DNA

• DNA is the repository of genetic information
• DNA is found in chromosomes—the structures in which genetic material is organized
• In eukaryotic cells, DNA is packaged around proteins called histones to form nucleosomes
• Bacteria lack a membrane-bound nucleus and thus DNA is found in the nucleoid region.

Structure of DNA

• DNA is a polymer of deoxyribonucleoside monophosphates linked through phosphodiester bonds.
• DNA exists as a double-stranded helix
  • The two strands wind around the central axis

Phosphodiester Bonds

• Phosphodiester bonds are the covalent bonds connecting nucleotides in a DNA strand or RNA strand—forming the “backbone” of the nucleic acid

Formation of the Phophosdiester Bonds

• The bonds form between the 3' hydroxyl group of one nucleotide and the 5' hydroxyl group of an adjacent nucleotide, releasing water.

DNA Structure/Conformation

• Complementary base-pairing (A-T, G-C) stabilizes the DNA double helix and is crucial for DNA replication.
• Antiparallel arrangement of strands in DNA
• Base stacking—hydrophobic interactions between bases

Watson-Crick Model

• Offset pairing of the two DNA strands; The two strands wind around an axis to form the double helix structure
• There are major and minor grooves within the helix,
• The double helix is stabilised by:
  • Metal cations shielding backbone charges.
  • Base stacking.
  • Van der Waals interactions

Double Helix

•  The two strands in the DNA helix are antiparallel, winding around a central axis
• The grooves in the DNA helix provide access for regulatory proteins.

Base Pairing

• Specific pairing of nitrogenous bases (A with T and G with C).

Bonding of Base Pairs

• The base pairs are held together by hydrogen bonds

Separation of the Two DNA Strands

• DNA strands separate when the hydrogen bonds between bases are disrupted; this can occur by altering pH or heating the solution
• Separation occurs at a temperature called the melting temperature (Tm).

Replication of DNA

• DNA replication involves separation of parent strands with each strand acting as a template

DNA Interaction with Proteins

• DNA interacts with proteins to form a complex structure, called chromatin, or chromosomes
• These proteins tightly package DNA to fit into the cell nucleus, ensuring that it is protected and controlled properly.

Histones and the Formation of Nucleosomes

• Histones are proteins with positive charges that bind tightly to negatively charged DNA, organizing it into condensed structures
• DNA wraps around histone octamer protein clusters, forming nucleosomes

Histones (Summary)

• Specific types of positively charged proteins
• Play a critical role in DNA organization.
• Binding to DNA causes DNA to coil into a compacted structure

Structure of RNA

• RNA is a single-stranded polymer of ribonucleotides linked through phosphodiester bonds

Types of RNA

• Three major types in protein synthesis—rRNA, tRNA, mRNA
  • rRNA : structural components of ribosomes (protein synthesis machines)
  • tRNA: adaptor molecules carrying amino acids to the ribosome
  • mRNA: carries the genetic code from the DNA to the ribosome

Messenger RNA (mRNA)

• mRNA carries the genetic instructions from DNA to direct protein synthesis
• mRNA comprises a polypeptide sequence specifying for a certain protein.

mRNA Structural Characteristics

• mRNA contains a 5’ cap, a coding region, and a poly-A tail
  • These special features help stabilize and translate the mRNA strand into a protein.
• Eukaryotic mRNA structure is unique and allows for efficient protein production.

Ribosomal RNA (rRNA)

• rRNAs are essential components of ribosomes
• rRNAs make up a large portion of the cell's total RNA

Transfer RNA (tRNA)

• tRNAs act as carriers for amino acids
• They use a specific structure (secondary and tertiary) and unique bases to accurately transport amino acids during protein synthesis