Nucleic Acids: Structure, Properties, and Biological Functions

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 and base composition.

• 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 acids contain two types of nitrogenous bases:

• Purines: Adenine (A) and Guanine (G)

• Pyrimidines: Cytosine (C), Thymine (T, in DNA), and 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 attached.

• Examples: Adenosine (nucleoside), Adenosine 5'-monophosphate (AMP) (nucleotide)

Properties of Nucleotides

Nucleotides possess several important chemical properties:

• Strong acids: Due to ionizable phosphate groups, nucleotides are strong acids.

• Ionization: Primary ionization occurs at low pH; secondary ionization and base protonation/deprotonation occur at neutral pH.

• Tautomerization: Bases can exist in different tautomeric forms (e.g., amino vs. imino, keto vs. enol).

• UV absorption: Nucleotides absorb light at ~260 nm, which is used to detect and quantify nucleic acids.

Phosphodiester Linkage

Nucleotides are joined by phosphodiester bonds to form the backbone of nucleic acid polymers.

• Nucleic acid synthesis involves activated nucleotides (e.g., nucleoside triphosphates).

• Phosphodiester bonds link the 3' hydroxyl group of one sugar to the 5' phosphate of the next.

4.2 Primary Structure of Nucleic Acids

Nature and Significance of Primary Structure

The primary structure of nucleic acids is the linear sequence of nucleotides, which encodes genetic information.

• Sequences are written from the 5' end to the 3' end.

• Example: 5'-ACGTT-3'

4.3 Secondary and Tertiary Structures of Nucleic Acids

Secondary Structure: The DNA Double Helix

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

• Watson and Crick proposed the double helix model, supported by X-ray diffraction data.

• Base pairing: Adenine pairs with Thymine (A=T), Guanine pairs with Cytosine (G≡C).

• Chargaff's rules: In DNA, %A = %T and %G = %C.

• Helical parameters: 10 base pairs per turn, 36° angle between stacked base pairs, 0.34 Å rise per base pair.

• Major and minor grooves: The double helix has alternating major and minor grooves important for protein binding.

Tertiary Structure: Supercoiling and Higher-Order Forms

Tertiary structure involves longer-range 3D interactions, such as supercoiling and cruciforms.

• Supercoiling: DNA can be twisted upon itself, affecting its compactness and biological function.

• Topoisomerases: Enzymes that modify DNA supercoiling, detectable by gel electrophoresis.

4.4 Alternative Secondary Structures of DNA

Palindromic Sequences, Hairpins, and Cruciforms

DNA can form alternative secondary structures due to specific sequences.

• Palindromic sequences: Symmetrical sequences that can form hairpins or cruciforms.

Triple-Stranded DNA and G-Quadruplexes

• Triple-stranded DNA: Involves Hoogsteen base pairing, forming triplex structures.

• G-quadruplexes: Structures formed by guanine-rich sequences, found in telomeres.

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

Denaturation of DNA

Denaturation refers to the separation of double-stranded DNA into single strands by heat or chemical agents.

• Denatured DNA has higher energy and is single-stranded.

• This process is reversible under appropriate conditions.

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

Storage and Flow of Genetic Information

Nucleic acids are central to the storage, transmission, and expression of genetic information.

• Storage: DNA stores the genome of an organism.

• Replication: DNA is copied for cell division and inheritance.

• Transcription: DNA is transcribed into messenger RNA (mRNA).

• Translation: mRNA is translated into proteins at ribosomes.

DNA Polymerase and Replication

• DNA polymerase: Enzyme that synthesizes new DNA strands during replication.

• Replication is semiconservative: each new DNA molecule contains one parental and one new strand.

Summary Table: Key Differences Between DNA and RNA

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

Key Equations

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

• Phosphodiester Bond Formation: $\text{Nucleotide}_n + \text{Nucleotide}_{n+1} \rightarrow \text{Nucleotide}_n\text{-}P\text{-}O\text{-}\text{Nucleotide}_{n+1}$

Example: UV Absorption for Nucleic Acid Quantification

Nucleic acids absorb UV light at 260 nm, allowing their concentration to be measured spectrophotometrically.

Additional info:

• RNA molecules such as tRNA have extensive regions of intramolecular complementarity, leading to complex tertiary structures.

• Alternative DNA structures (e.g., G-quadruplexes) play roles in chromosome stability and regulation.