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4.1 Nucleic Acids - Informational Macromolecules

Introduction to Nucleic Acids

Nucleic acids are essential informational macromolecules that store and transmit genetic information in all living organisms. The two main types are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

• DNA stores genetic information and is found primarily in the cell nucleus.

• RNA is involved in protein synthesis and gene regulation, and is found in various cellular locations.

Chemical Structures of DNA and RNA

Both DNA and RNA are polymers of nucleotides, but differ in their sugar components and bases.

• DNA contains deoxyribose sugar; RNA contains ribose sugar.

• DNA uses the bases adenine (A), guanine (G), cytosine (C), and thymine (T); RNA uses uracil (U) instead of thymine.

Purine and Pyrimidine Bases

Nucleic acid bases are classified as purines or pyrimidines:

• Purines: Adenine (A), Guanine (G)

• Pyrimidines: Cytosine (C), Thymine (T, in DNA), Uracil (U, in RNA)

Nucleosides and Nucleotides

A nucleoside consists of a nitrogenous base linked to a sugar. A nucleotide is a nucleoside with one or more phosphate groups.

Type	Example (Purine)	Example (Pyrimidine)
Nucleoside	Adenosine, Guanosine	Cytidine, Uridine
Nucleotide	AMP (Adenosine 5'-monophosphate), GMP (Guanosine 5'-monophosphate)	CMP (Cytidine 5'-monophosphate), UMP (Uridine 5'-monophosphate)

Properties of Nucleotides

Acidic Nature and Ionization

• Nucleotides are strong acids due to the ionizable phosphate group.

• Primary ionization occurs at low pH (~1.0); secondary ionization and base protonation/deprotonation occur at neutral pH.

Tautomeric Forms

Bases can exist in different tautomeric forms, affecting hydrogen bonding:

• Amino vs. Imino (e.g., adenine, cytosine)

• Keto vs. Enol (e.g., guanine, thymine)

UV Absorption

• Nucleotides absorb light in the UV range, especially around 260 nm.

• This property is used to detect and quantify nucleic acids in solution.

Phosphodiester Linkage

Nucleic Acid Synthesis

Nucleotides are joined by phosphodiester bonds between the 3' hydroxyl of one sugar and the 5' phosphate of the next.

• Synthesis uses activated nucleotides (e.g., nucleoside triphosphates).

• Phosphodiester bonds form the backbone of DNA and RNA.

4.2 Primary Structure of Nucleic Acids

Sequence and Directionality

The primary structure of nucleic acids is the linear sequence of nucleotides, written from the 5' to 3' end.

• Example: 5'-ACGTT-3'

• Conventional representation places the 5' end to the left.

4.3 Secondary and Tertiary Structures of Nucleic Acids

Secondary Structure: The DNA Double Helix

Secondary structure refers to the 3D arrangement of nucleotide residues, such as the double helix in DNA.

• Watson and Crick's model (1953) described the double helix structure.

• X-ray diffraction (Rosalind Franklin) provided evidence for helical structure.

Base Pairing and Chargaff's Rules

• DNA base pairs: A=T and G≡C

• Chargaff's rules: $\text{mole \%}~A = T,~G = C$

Helical Parameters

• Angle between stacked base pairs: 36°

• Number of base pairs per turn: 10 bp/turn

• Rise per base pair: 0.34 Å

Major and Minor Grooves

• The double helix has major and minor grooves important for protein-DNA interactions.

Tertiary Structure: Supercoiling and Higher-Order Forms

• Supercoiling increases DNA compactness and is regulated by topoisomerases.

• Superhelical forms include cruciforms and other complex structures.

Semiconservative Nature of DNA Replication

DNA Replication Mechanism

• Each strand of the parent DNA serves as a template for a new, complementary strand.

• Three initial models: semiconservative, conservative, and dispersive replication.

Alternative Nucleic Acid Structures

B and A Helices

• B form is the most common DNA structure in cells.

• A form is found in double-stranded RNA and DNA-RNA hybrids.

Palindromic Sequences, Hairpins, and Cruciforms

• Palindromic DNA sequences are symmetrical and can form hairpin or cruciform structures.

Triple-Stranded DNA and G-Quadruplexes

• Triple-stranded DNA can form via Hoogsteen base pairing.

• G-quadruplexes are found in telomeres and involve stacks of guanine quartets.

Single-Stranded Polynucleotides

Common Conformations

• Most DNA is double-stranded; most RNA is single-stranded.

• Single-stranded nucleic acids can adopt various conformations, including random coils and regions of self-complementarity.

Transfer RNA (tRNA) Structure

• tRNA has extensive intramolecular complementarity, forming a cloverleaf secondary structure and a compact tertiary structure.

• Structure determined by X-ray diffraction.

4.5 The Helix-to-Random Coil Transition: Nucleic Acid Denaturation

Denaturation of DNA

• Heating double-stranded DNA causes denaturation, separating it into two single strands.

• Denatured DNA has higher energy and different physical properties.

4.6 The Biological Functions of Nucleic Acids: A Preview of Genetic Biochemistry

Genetic Information Flow

• DNA stores the genetic information of an organism (genome).

• Replication passes genetic information from cell to cell and generation to generation.

• Transcription converts DNA information into messenger RNA (mRNA).

• Translation uses mRNA to synthesize proteins at ribosomes.

DNA Polymerase and Replication

• DNA polymerase is a key enzyme in the replisome complex, responsible for DNA replication.

Summary Table: Key Features of DNA and RNA

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, T, G, C	A, U, G, C
Strandedness	Double-stranded	Single-stranded (mostly)
Main Function	Genetic information storage	Protein synthesis, gene regulation

Additional info: The notes expand on the original slides by providing definitions, context, and examples for each concept, ensuring a self-contained study guide suitable for biochemistry students.