Nucleic Acids: Structure, Properties, and Biological Functions

Nucleic Acids—Informational Macromolecules

Introduction to Nucleic Acids

Nucleic acids are large biomolecules essential for all known forms of life. They serve as the carriers of genetic information and play a central role in cellular processes such as replication, transcription, and translation. The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

• DNA stores genetic information in cells and is responsible for heredity.

• RNA is involved in protein synthesis and the regulation of gene expression.

Types of Nucleic Acid: DNA and RNA

Chemical Structure of DNA and RNA

Both DNA and RNA are polymers composed of nucleotide monomers. Each nucleotide consists of three components: a nitrogenous base, a five-carbon sugar, and a phosphate group. The chemical structure of the sugar differs between DNA and RNA.

• DNA contains deoxyribose sugar (lacking an oxygen atom at the 2' position).

• RNA contains ribose sugar (with an OH group at the 2' position).

• Carbon atoms in the sugar are designated by primes (1', 2', etc.).

Example: Chemical Structures

• DNA: Repeating unit of deoxyribonucleotide (deoxyribose + phosphate + base)

• RNA: Repeating unit of ribonucleotide (ribose + phosphate + base)

Nitrogenous Bases in DNA and RNA

Purine and Pyrimidine Bases

Nucleic acids contain two types of nitrogenous bases: purines and pyrimidines. These bases are responsible for the coding properties of nucleic acids and participate in hydrogen bonding that stabilizes the double helix structure.

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

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

Example: Base Structures

• Adenine and Guanine are double-ring structures (purines).

• Cytosine, Thymine, and Uracil are single-ring structures (pyrimidines).

Nucleosides and Nucleotides

Definitions and Structures

A nucleoside consists of a nitrogenous base linked to a five-carbon sugar. A nucleotide is a nucleoside with one or more phosphate groups attached. Nucleotides are the building blocks of nucleic acids.

• Nucleoside: Base + Sugar (e.g., Adenosine = Adenine + Ribose)

• Nucleotide: Nucleoside + Phosphate (e.g., Adenosine 5'-monophosphate)

Example: Nucleoside and Nucleotide Structures

• Adenosine (nucleoside) vs. Adenosine 5'-monophosphate (nucleotide)

• Guanosine (nucleoside) vs. Guanosine 5'-monophosphate (nucleotide)

Properties of Nucleotides

Acid-Base Properties and Tautomerization

Nucleotides are strong acids due to the ionization of their phosphate groups. The nitrogenous bases can exist in different tautomeric forms, which can affect base pairing and the stability of nucleic acids.

• Primary ionization: Phosphate group loses a proton at low pH.

• Secondary ionization: Occurs at neutral pH, affecting the amino groups on the bases.

• Tautomerization: Bases can shift between keto and enol forms, or amino and imino forms.

Ultraviolet Absorption

Nucleotides absorb ultraviolet (UV) light, which is used to detect and quantify nucleic acids in laboratory settings.

• Maximum absorption typically occurs at wavelengths around 260 nm.

Phosphodiester Linkage

Formation and Stability

Nucleotides are linked together by phosphodiester bonds between the 3' hydroxyl group of one sugar and the 5' phosphate group of the next. This linkage forms the backbone of DNA and RNA strands.

• Phosphodiester bonds provide stability and directionality to nucleic acid chains.

• Polar molecules like nucleic acids have dipole moments and interact with ions and other polar molecules in aqueous environments.

Alkaline Hydrolysis of RNA

RNA is susceptible to hydrolysis under alkaline conditions due to the presence of the 2' hydroxyl group, which can attack the phosphodiester bond and form a cyclic intermediate. This reaction does not occur in DNA.

Primary Structure of Nucleic Acids

Sequence and Significance

The primary structure of nucleic acids refers to the linear sequence of nucleotides. This sequence encodes genetic information and determines the function of the molecule.

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

• Example: 5'-ACGTT-3'

DNA as the Genetic Substance

Historical Experiments

Experiments by Avery, Hershey, and Chase demonstrated that DNA is the genetic material responsible for heredity.

• Avery's experiment: Showed that DNA from pathogenic bacteria could transform non-pathogenic strains.

• Hershey-Chase experiment: Used bacteriophages to show that DNA, not protein, is transferred to bacteria during infection.

Secondary and Tertiary Structures of Nucleic Acids

DNA Double Helix

The secondary structure of DNA is the double helix, formed by two complementary strands held together by hydrogen bonds between base pairs. The tertiary structure involves further folding and supercoiling.

• Base pairing follows Chargaff's rules: %A = %T and %G = %C.

• 10 base pairs per turn of the helix; each base pair is separated by 0.34 nm.

• Major and minor grooves are present in the double helix.

Semiconservative Nature of DNA Replication

Models and Experimental Evidence

DNA replication is semiconservative, meaning each new DNA molecule consists of one parental and one newly synthesized strand. The Meselson-Stahl experiment provided evidence for this mechanism.

• DNA grown in heavy nitrogen (15N) and then transferred to light nitrogen (14N) showed intermediate density after one generation, consistent with semiconservative replication.

Alternative Nucleic Acid Structures

Forms of DNA Helices

DNA can adopt different helical forms, primarily the B-form (most common in cells) and the A-form (found under dehydrating conditions).

• B-form: Right-handed helix, 10 bp per turn.

• A-form: Right-handed helix, more compact, 11 bp per turn.

Supercoiling and Single-Stranded Conformations

DNA and RNA molecules can be supercoiled or exist in single-stranded conformations. Supercoiling affects the compactness and function of nucleic acids.

• Topoisomerases are enzymes that modify the supercoiling state of DNA.

• Single-stranded RNA can fold into complex structures due to internal complementarity (e.g., tRNA).

Helix-to-Random Coil Transition: Nucleic Acid Denaturation

Denaturation and Renaturation

Double-stranded DNA can be separated into single strands by heat, alkali, or other denaturing agents. This process is reversible, and renaturation occurs upon cooling.

• Denaturation is cooperative and occurs over a narrow temperature range.

• Denatured DNA absorbs more UV light than native DNA.

Biological Functions of Nucleic Acids

Genetic Information Flow

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

• Replication: DNA is copied for cell division.

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

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

Tools of Biochemistry: Manipulating DNA

Biochemical Applications

Modern biochemistry uses various techniques to manipulate DNA for research and biotechnology.

• Gene cloning

• Chemical synthesis of oligonucleotides

• DNA sequence analysis (e.g., Sanger sequencing)

• Site-directed mutagenesis

• Polymerase chain reaction (PCR)

Example: DNA Sequencing

• Sanger method uses base-specific termination reactions and fluorescently labeled nucleotides to determine DNA sequence.

Summary Table: Nitrogenous Bases in DNA and RNA

Base	Type	Found in DNA?	Found in RNA?
Adenine (A)	Purine	Yes	Yes
Guanine (G)	Purine	Yes	Yes
Cytosine (C)	Pyrimidine	Yes	Yes
Thymine (T)	Pyrimidine	Yes	No
Uracil (U)	Pyrimidine	No	Yes

Key Equations

• Phosphodiester bond formation: $\text{Nucleotide}_n + \text{Nucleotide}_{n+1} \rightarrow \text{Nucleotide}_n - \text{phosphodiester bond} - \text{Nucleotide}_{n+1}$

• Chargaff's rules: $\%A = \%T$ $\%G = \%C$

• DNA helix rise per base pair: $\text{Rise per base pair} = 0.34\ \text{nm}$

Additional info: Some context and explanations have been expanded for clarity and completeness.