Nucleic Acids: Structure, Properties, and Biological Functions

4.1 Nucleic Acids – Informational Macromolecules

Introduction to Nucleic Acids

• Nucleic acids are large biomolecules essential for all known forms of life, serving as the carriers of genetic information.

• There are two main types: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

• Both DNA and RNA are polymers of nucleotides, but differ in sugar type and certain bases.

Chemical Structures of DNA and RNA

• DNA contains deoxyribose sugar; RNA contains ribose sugar.

• Both have a phosphate backbone and nitrogenous bases.

• DNA is typically double-stranded; RNA is usually single-stranded.

Nitrogenous Bases

• Bases are classified as purines (adenine, guanine) and pyrimidines (cytosine, thymine, uracil).

• DNA contains adenine (A), guanine (G), cytosine (C), and thymine (T).

• RNA contains adenine (A), guanine (G), cytosine (C), and uracil (U) instead of thymine.

Nucleosides and Nucleotides

• Nucleoside: base + sugar (ribose or deoxyribose).

• Nucleotide: nucleoside + phosphate group(s).

• Examples: Adenosine (nucleoside), Adenosine monophosphate (AMP, nucleotide).

Properties of Nucleotides

Acid-Base Properties

• Nucleotides are strong acids due to the phosphate group.

• Primary ionization of phosphate occurs at low pH (~1.0).

• Secondary ionization and base protonation/deprotonation occur near neutral pH.

Tautomerization

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

• Tautomerization can affect base pairing and mutagenesis.

UV Absorption

• Nucleotides absorb ultraviolet light maximally at around 260 nm.

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

Phosphodiester Linkage

Nucleic Acid Polymerization

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

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

4.2 Primary Structure of Nucleic Acids

Nature and Significance

• The primary structure is the linear sequence of nucleotides in a nucleic acid chain.

• Sequences are written from the 5' end to the 3' end (e.g., 5'-ACGTT-3').

• This sequence encodes genetic information.

4.3 Secondary and Tertiary Structures of Nucleic Acids

Secondary Structure: The DNA Double Helix

• Secondary structure refers to local 3D arrangements, such as the double helix in DNA.

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

• Base pairing: A pairs with T (or U in RNA), G pairs with C.

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

• Helix characteristics: 10 base pairs per turn, 36° rotation per base pair, 0.34 nm rise per base pair.

• Major and minor grooves are present in the helix, important for protein binding.

Tertiary Structure

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

Semiconservative DNA Replication

• Each DNA strand serves as a template for a new complementary strand during replication.

• Three models were proposed: semiconservative (correct), conservative, and dispersive.

Alternative DNA Helices

• B-form DNA is the most common in cells; A-form is found in double-stranded RNA and DNA-RNA hybrids.

DNA and RNA Molecules In Vivo

Visualization and Topology

• DNA can be visualized by electron microscopy.

• DNA exists in relaxed and supercoiled forms; supercoiling compacts DNA and affects its function.

• Topoisomerases are enzymes that modify DNA supercoiling, which can be analyzed by agarose gel electrophoresis.

Single-Stranded Polynucleotides

RNA Structure

• Most cellular DNA is double-stranded, but most RNA is single-stranded.

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

• tRNA molecules have extensive intramolecular base pairing, forming complex tertiary structures.

4.4 Alternative Secondary Structures of DNA

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 four-stranded structures found in telomeres, stabilized by guanine-rich sequences.

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

Denaturation of DNA

• Heating double-stranded DNA separates it into two single strands (denaturation), increasing the energy state.

• This process is reversible (renaturation or annealing).

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

Genetic Information Flow

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

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

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

• Translation: mRNA is used as a template to synthesize proteins at ribosomes.

Key Enzymes

• DNA polymerase is the enzyme responsible for DNA replication, part of the replisome complex.

Table: Comparison of 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)
Main Function	Genetic information storage	Information transfer and protein synthesis

Key Equations

• Chargaff's Rule:

$\text{mole \%}~A = T~\text{and}~G = C$

• Phosphodiester Bond Formation:

$\text{(Nucleotide)}_{n} + \text{NTP} \rightarrow \text{(Nucleotide)}_{n+1} + PP_i$

• UV Absorbance for Nucleic Acid Quantification:

$A_{260} = \varepsilon \cdot c \cdot l$

where $A_{260}$ is absorbance at 260 nm, $\varepsilon$ is the molar extinction coefficient, $c$ is concentration, and $l$ is path length.

Additional info: This summary integrates textbook-level explanations and expands on the provided slides for clarity and completeness.