biochem week 13 part 2

Introduction to the importance of oxygen in cellular functions.
Mention of EPO (Erythropoietin) as a topic previously covered.
Clarification that slides from previous session will be posted for reference but are not part of the test material.

Explanation of tRNA (transfer RNA) functionality:
- Each tRNA molecule carries a specific amino acid on one end and contains an anticodon on the other end.
- The anticodon is complementary to a specific codon in mRNA, ensuring accurate translation during protein synthesis.
Example provided:
- Codon pair: AUG (start codon in mRNA) and UAC (anticodon in tRNA).
Importance of hydrogen bonds:
- Dotted lines indicating hydrogen bonds between codon and anticodon ensure correct tRNA binding.
Reading direction of mRNA during translation:
- mRNA is translated from the 5' to the 3' direction.
- Start codon located at the 5' end for translation initiation.

Clarification of nucleic acid structure:
- 5' and 3' designations relate to deoxyribose or ribose sugar structure.
Polypeptide structure explained:
- Contains an amino terminus (N-terminus) and a carboxy terminus (C-terminus).
- The first amino acid has a free amino group, indicating the N-terminus.
The exercise focuses on a specific sequence of a gene, excluding initial landmarks like the start codon (AUG).
- Students should understand that their focus is on an established reading frame beyond the start codon.

Reminder for practice worksheets related to identifying codons and translating sequences.
Specific terminology outlined for questions:
- For mRNA sequence translation: Identify and designate amino acid sequences along N-terminus and C-terminus.
- Note on sequence complexity: "Writing these out is like doing a puzzle," emphasizing precision in notation.

Discussion initiated about single-base substitutions.
- Example mutation: A to C transformation leading to the condition MMA (methylmalonic acidemia).
Clarification of sequence reading for questions.
Categories of mutations delineated:
  - Silent mutations: Do not result in changes to the polypeptide sequence.
  - Missense mutations: Result in a change to a single amino acid.
  - Nonsense mutations: Introduce a premature stop codon leading to truncated proteins.
Real-world implications of mutations discussed, including their significance in clinical contexts.

Transition into discussing practical examples of genetic mutations in clinical case studies.
Importance of collaboration and peer support emphasized in problem-solving exercises.
Mention of practical tools: ELC (e-learning platform) for accessing materials.

Expounded on the techniques of mutation repair and detection through DNA polymerase mechanisms and mismatch repair systems.
Baseline definition of mutations established, such as base substitutions, insertions, and deletions.
Concrete examples of point mutations provided, illustrating various outcomes:
- Base substitution cases exemplified.
- IIT (injected into transgenic models) cases discussed for practical relevance.

Detailed exploration of current treatment strategies for genetic disorders like MMA.
- Contrast between dietary management and enzyme replacement therapy limitations discussed.
Introduction into mRNA therapy as a novel approach:
  - Concept of injecting modified mRNA that encodes the required enzyme.
  - Benefits of leveraging the body’s translational machinery presented.
  - Key historical context provided on the evolution of treatment options for MMA.

Outline of ongoing mouse model studies that explore the feasibility of mRNA treatments:
- Intravenous injection to study effects on liver functioning and health metrics.
- Key physiological metrics (e.g., methylmalonic acid levels) form focal points for evaluating treatment efficacy.
Emphasis on the importance of controlling groups in experimental designs and statistical analyses.
Sequence of steps in synthesizing mRNA before injection listed:
- Optimizing for codon usage, adding untranslated regions, and ensuring stability with five prime caps and poly A tails.
Challenges of ensuring sustained enzyme functionality post-injection acknowledged.

Discussion around the need for continual monitoring of injected mRNA outcomes.
Suggestions for potential adaptations in treatment protocols for human patients inferred based on observed mouse study results.
Closing remarks encouraging students to engage with assigned readings and actively participate in the next session.

Reinforcement of course objectives, including transcription and translation mechanisms.
Assignment reminders and encouragement to approach upcoming content with confidence and collaboration.
Adjournment and motivation for the next class meeting.