Components of Nucleic Acids

• The general structure of a nucleotide includes:
    - Nitrogen-containing base
    - Sugar
    - Phosphate group

Nucleic Acids

• There are two types of nucleic acids:
    - Deoxyribonucleic acid (DNA): The genetic material found in the nucleus of a cell.
    - Ribonucleic acid (RNA): Interprets genetic information in DNA for protein synthesis.
• Both types are unbranched polymers made of repeating monomer units known as nucleotides.
• Each nucleotide comprises:
    - A base containing nitrogen
    - A five-carbon sugar
    - A phosphate group
• General characteristics of nucleic acids:
    - Large molecules
    - Found in the nuclei of cells
    - Store information and direct activities for cellular growth and reproduction.

Bases in Nucleic Acids

• Bases in DNA and RNA are derivatives of heterocyclic amines characterized as:
    - Pyrimidines: Single ring containing two nitrogen atoms.
    - Purines: Double rings, each containing two nitrogen atoms.
    - Bases act as H+ acceptors at nitrogen atoms.

Bases in DNA

• Purine Bases:
    - Adenine (A)
    - Guanine (G)
• Pyrimidine Bases:
    - Cytosine (C)
    - Thymine (T)

Bases in RNA

• Purine Bases:
    - Adenine (A)
    - Guanine (G)
• Pyrimidine Bases:
    - Cytosine (C)
    - Uracil (U)

Pentose Sugars in Nucleotides

• The five-carbon sugar differs between RNA and DNA:
    - In RNA: Ribose
    - In DNA: Deoxyribose (lacks O atom on C2′)
• Carbon atoms in the sugar are numbered with primes to differentiate from the atoms in the bases.

Nucleosides

• A nucleoside comprises:
    - A nitrogen-containing base
    - A sugar (either ribose or deoxyribose)
• The base is linked to C1′ of the sugar by a β-N-glycosidic bond.

Nucleotides

• A nucleotide possesses:
    - A phosphate group attached to the C5′ — OH group of a nucleoside.
• The process of adding a phosphate to a nucleoside generates a nucleotide.

Primary Structure of Nucleic Acids

• In the primary structure:
    - Nucleotides are joined by phosphodiester bonds.
    - The 3′ —OH group of the sugar in one nucleotide links to the phosphate group on the 5′ carbon atom of another nucleotide.

Base Sequence and Primary Structure

• Each nucleic acid has a unique sequence of bases known as:
    - Primary Structure: Carries genetic information.
    - Read from the sugar with the free 5′ phosphate to the sugar with the free 3′ —OH group.
    - Typical notation: 5′ ACGT 3′.
• In primary structure of RNA, the bases A, C, G, and U are linked by 3′,5′ phosphodiester linkages.

DNA Double Helix and Replication

• Structure:
    - DNA forms a double helix comprising two nucleotide strands.
    - Two strands create a structure likened to a spiral staircase, with hydrogen bonds between complementary base pairs.
    - Adenine (A) pairs with Thymine (T) and Guanine (G) pairs with Cytosine (C).
• The pairing ratio establishes:
    - Adenine = Thymine (1:1)
    - Guanine = Cytosine (1:1)
• Summary of base pairing: Number of purines equals number of pyrimidines.

Complementary Base Pairs

• A and T: Adenine is linked to thymine by two hydrogen bonds (AT).
• G and C: Guanine is linked to cytosine by three hydrogen bonds (GC).

DNA Replication

• Function of DNA:
    - Preserve genetic information.
    - Transfer genetic information to new cells.
• During replication:
    - Parent DNA strands separate, allowing for synthesis of new complementary strands.
    - The process starts with unwinding the double helix by breaking hydrogen bonds between complementary bases.

Mechanism of DNA Replication

• Nucleoside triphosphates (dATP, dTTP, dGTP, dCTP) bond with complementary bases in the nucleus while forming hydrogen bonds.
• Phosphodiester linkages between nucleotides establish complete daughter strands.
• Each new DNA consists of one strand from parent DNA and one newly synthesized strand, ensuring the formation of two exact copies of parent DNA.

Direction of Replication

• Helicase unwinds the DNA at multiple points, while DNA polymerase catalyzes replication:
    - Moves in 3′–5′ direction, forming new links.
    - Synthesizes the lagging strand in short segments (Okazaki fragments).
    - DNA ligase joins Okazaki fragments.

RNA and Transcription

• Ribosome structure includes a small subunit and large subunit, containing protein and rRNA.
• RNA characteristics:
    - Most nucleic acid present in the cell.
    - Transmits genetic information from DNA.
    - Differences from DNA:
      - Sugar: Ribose (RNA) vs. Deoxyribose (DNA)
      - Base: Uracil (RNA) replaces Thymine (DNA)
      - Structure: Single-stranded (RNA) vs. Double-stranded (DNA)
      - Size: RNA is smaller than DNA.

Types of RNA

• Types of RNA categorized by abundance and function:
    - Messenger RNA (mRNA): makes up 5% of RNA, carries genetic information from DNA to ribosomes.
    - Transfer RNA (tRNA): comprises 15% of RNA, translates mRNA information into amino acid sequences.
    - Ribosomal RNA (rRNA): accounts for 80% of RNA, most abundant, combines with proteins to form ribosomes.

tRNA Structure

• Typical tRNA appears as:
    - A cloverleaf in two dimensions and L-shaped in three dimensions.
    - Contains an acceptor stem at 3′ end with the nucleotide sequence ACC for amino acid attachment via an ester bond.
    - Holds an anticodon, a three-base series complementing mRNA codons.

RNA and Protein Synthesis

• Genetic information for protein synthesis:
    - Copied from DNA gene in the nucleus.
    - mRNA is synthesized in transcription and moves into the cytosol.
    - mRNA binds to ribosomes where tRNA converts mRNA information into amino acids during translation.

Transcription Process

• In transcription:
    - DNA unwinds around the target gene.
    - RNA polymerase forms new mRNA using the DNA template strand while adhering to complementary base pairing (U replaces T).
• After transcription, mRNA exits the nucleus to reach the cytoplasm.

The Genetic Code and Protein Synthesis

• Function of RNA types in protein synthesis:
    - Facilitates tasks to synthesize proteins.
• Steps of protein synthesis:
    1. Transcription of genetic information from DNA, leading to mature mRNA.
    2. mRNA exits the nucleus, binding to ribosomes; genetic information is translated into an amino acid sequence of proteins.

Genetic Code Overview

• Genetic code consists of triplets in mRNA (codons) specifying amino acids, including:
    - 20 amino acids, each with specific codons.
    - Start codon: AUG (signals beginning).
    - Stop signals: UGA, UAA, UAG (signals termination).

Codons and Amino Acids Example

For mRNA section 5′ CCU AGC GGA CUU 3′:

• Using genetic code:
    - CCU = Proline
    - AGC = Serine
    - GGA = Glycine
    - CUU = Leucine
• The resulting amino acid sequence: Pro—Ser—Gly—Leu.

Protein Synthesis in Detail

• tRNA Activation:
    - tRNA gains specific amino acids based on anticodons.
• Initiation and Elongation:
    - Start codon (C) binds tRNA, ribosomes translate genetic information to form a protein chain through peptide bonds.
• Termination:
    - Encountering a stop codon signals halt in polypeptide synthesis, releasing the polypeptide from the ribosome. tRNA returns for recharging with new amino acids.

Genetic Mutations

• A mutation is:
    - Change in the nucleotide sequence of DNA affecting amino acid sequences, potentially altering cell structure and function.
    - Result of mutagens: radiation, chemicals, possibly some viruses.

Types of Mutation

• Point Mutation: A single base is changed, possibly altering one amino acid in a polypeptide.
• Silent Mutation: A point mutation that doesn't change the amino acid sequence.
• Deletion Mutation: Base removal alters reading frame, changing all downstream amino acids.
• Insertion Mutation: Addition of a base alters reading frame, changing all downstream amino acids.

Effects of Mutations

• Not all mutations create significant protein changes.
• Severe mutations can result in:
    - Loss of biological activity
    - Enzyme dysfunction, leading to toxic substance accumulation within cells.

Genetic Diseases

• Arise from defective enzymes due to mutations.
• Example: Defective enzyme converting tyrosine into melanin leads to albinism, affecting pigmentation.

Viruses

• Viruses are small entities consisting of RNA or DNA, needing a host cell for replication.
• Example: Epstein–Barr virus (EBV) associated with cancers in humans.

Mechanism of Viral Infections

1. A viral enzyme penetrates the host cell wall to enable entry.
2. Viral nucleic acid integrates with host cell materials.
3. Proteins are processed to form a new viral coat for RNA/DNA.
4. Released new viral particles infect additional cells.

Reverse Transcription (Retroviruses)

• In reverse transcription:
    - Viral RNA enters host cell.
    - RNA is converted to DNA (provirus) using reverse transcriptase and subsequently integrated into host DNA.
    - Provirus replication generates new viral RNA for new virions.

HIV/AIDS Treatment

• Treatment for AIDS focuses on targeting HIV lifecycle.
• Development of nucleoside analogs mimics natural nucleosides used in DNA synthesis:
    - Examples include AZT similar to thymidine, ddI similar to guanosine, and others.
• Nucleoside analog incorporation leads to halted viral DNA synthesis due to lack of critical hydroxyl groups on nucleosides.

Current Treatments for HIV/AIDS

• Combination therapies involving:
    - Entry inhibitors
    - Reverse transcriptase inhibitors
    - Protease inhibitors

Chemistry Link to Health: Cancer

• Uncontrolled cell growth results in tumors, which can be benign or malignant.
• Causes of cancer:
    - Environmental factors, such as carcinogenic chemicals, radiation, and viruses like EBV.

Cancer Prevention

• Awareness of carcinogenic substances, including chemical exposure (aniline dyes, cigarette smoke) supports cancer prevention strategies.