Assignment no.6 (biochemistry)

 

**SAQ**

1. **Genetic Code and Wobble Hypothesis for Codon-Anticodon Interactions**

   **Genetic Code**:

   - The genetic code is a set of rules by which information encoded in DNA or mRNA sequences is translated into proteins by living cells. It is universal, nearly identical among all organisms, and consists of 64 codons.

   - Codons are sequences of three nucleotides, each codon specifies a particular amino acid.

   - There are 61 codons for amino acids and 3 stop codons (UAA, UAG, UGA) which signal the termination of protein synthesis.

   **Wobble Hypothesis**:

   - Proposed by Francis Crick, the wobble hypothesis explains the flexibility in the base-pairing rules between the 5' base of the tRNA anticodon and the 3' base of the mRNA codon.

   - The third base of the codon (3’ end) and the first base of the anticodon (5’ end) can form non-standard pairings, allowing a single tRNA to recognize multiple codons.

   - For example, inosine in the tRNA anticodon can pair with U, C, or A in the mRNA codon, contributing to the degeneracy of the genetic code.

2. **Applications of Recombinant DNA Technology**

   - **Medical Applications**: Production of insulin, growth hormones, vaccines (e.g., hepatitis B vaccine), gene therapy for genetic disorders, and monoclonal antibodies for disease treatment.

   - **Agricultural Applications**: Development of genetically modified crops with enhanced nutritional content, resistance to pests and diseases, and tolerance to herbicides.

   - **Industrial Applications**: Production of enzymes for detergents, biofuels, and bioplastics, and fermentation processes for producing bioethanol.

   - **Environmental Applications**: Bioremediation techniques using genetically engineered microorganisms to clean up oil spills and toxic waste.

3. **Purine Salvage Pathway and Gout**

   **Purine Salvage Pathway**:

   - The purine salvage pathway recycles purines (adenine and guanine) from degraded nucleic acids back into nucleotide form.

   - Enzymes involved include adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT).

   - APRT converts adenine to AMP, and HGPRT converts hypoxanthine to IMP and guanine to GMP.

   **Gout**:

   - Gout is a form of arthritis characterized by sudden, severe attacks of pain, redness, and tenderness in joints, caused by elevated levels of uric acid in the blood.

   - Uric acid crystals can accumulate in joints, causing inflammation and pain.

   - Overproduction or under-excretion of uric acid, often linked to genetic factors or dietary habits, can lead to gout.

   - Treatments include medications to reduce uric acid levels and anti-inflammatory drugs to manage symptoms.

4. **Tumor Markers and Their Clinical Significance**

   - **Alpha-fetoprotein (AFP)**: Elevated in liver cancer and germ cell tumors.

   - **Carcinoembryonic antigen (CEA)**: Elevated in colorectal cancer and other gastrointestinal cancers.

   - **Prostate-specific antigen (PSA)**: Elevated in prostate cancer.

   - **CA-125**: Elevated in ovarian cancer.

   - **CA 19-9**: Elevated in pancreatic cancer.

   - **Human chorionic gonadotropin (hCG)**: Elevated in gestational trophoblastic disease and germ cell tumors.

   - **Bence Jones protein**: Presence in multiple myeloma.

   - Tumor markers are used for screening, diagnosis, prognosis, and monitoring treatment response.

**LAQ**

1. **Protein Biosynthesis with Diagrammatic Representation and Post Translational Modifications**

   **Protein Biosynthesis**:

   - **Initiation**: The small ribosomal subunit binds to mRNA at the start codon (AUG), and the initiator tRNA carrying methionine pairs with the start codon.

   - **Elongation**: The ribosome moves along the mRNA, adding amino acids to the growing polypeptide chain by forming peptide bonds between amino acids brought by tRNAs.

   - **Termination**: When a stop codon is encountered, release factors bind to the ribosome, prompting the release of the newly synthesized protein and dissociation of the ribosome subunits.

   **Diagrammatic Representation**:

   - Include diagrams showing the initiation complex formation, elongation cycle, and termination process.

   **Post Translational Modifications (PTMs)**:

   - **Phosphorylation**: Addition of phosphate groups to serine, threonine, or tyrosine residues by kinases.

   - **Glycosylation**: Attachment of sugar moieties to asparagine (N-linked) or serine/threonine (O-linked) residues.

   - **Acetylation**: Addition of acetyl groups to lysine residues, often on histones, affecting gene expression.

   - **Ubiquitination**: Addition of ubiquitin molecules, targeting proteins for degradation by the proteasome.

   - **Proteolytic Cleavage**: Removal of signal peptides or activation of pro-proteins into functional forms.

2. **Replication in Eukaryotes and Clinical Applications of DNA Replication Inhibitors**

   **Replication in Eukaryotes**:

   - **Initiation**: Multiple origins of replication; origin recognition complex (ORC) binds to replication origins, recruiting helicases to unwind DNA.

   - **Elongation**: DNA polymerases α, δ, and ε synthesize new DNA strands; leading strand synthesized continuously, lagging strand synthesized discontinuously as Okazaki fragments.

   - **Termination**: Ends of linear chromosomes maintained by telomerase, which extends telomeres to prevent loss of genetic information.

   **Diagrammatic Representation**:

   - Include diagrams showing the origin of replication, formation of replication fork, leading and lagging strand synthesis, and role of telomerase.

   **Clinical Applications of DNA Replication Inhibitors**:

   - **Chemotherapeutic Agents**: Drugs like doxorubicin, etoposide, and cisplatin inhibit DNA replication in rapidly dividing cancer cells, slowing tumor growth.

   - **Antiviral Drugs**: Nucleotide analogs like acyclovir inhibit viral DNA polymerase, used in treating herpes simplex virus infections.

   - **Antibiotics**: Quinolones like ciprofloxacin inhibit bacterial DNA gyrase, essential for bacterial DNA replication, used to treat bacterial infections.