11/4 NOTE- NUCLEIC ACIDS

Lab Updates and Assignments

• Dai Amalan's Experiment: Two groups returning today.

• Lab Report: Due Sunday; formal report details available on Canvas.

• Assignments:

  • One perusal assignment due last night (nucleic acid structure).

  • Second perusal assignment due Tuesday night (DNA replication).

• Exam Reminder: Exam 5 scheduled for one week from today covering:

  • Citric Acid Cycle

  • Oxidative Phosphorylation

  • Structure of nucleic acid

  • DNA Replication

Cellular Respiration Overview

Oxidative Phosphorylation & Electron Transport Chain

• Role of ATP Synthase: Produces ATP by utilizing the proton gradient.

• Proton Gradient Mechanism:

  • ATP synthase acts as a turbine; protons flow down the gradient to drive ATP production.

• Effect of DNP:

  • DNP inserts into mitochondrial membrane, allowing protons to bypass ATP synthase, decreasing ATP production.

ATP Yield Calculation

• Theoretical Maximum: 38 ATP per glucose in ideal situations.

• Realistic Production: Typically, ~30 ATP due to cellular adaptations using other transport proteins.

• ATP synthesis:

  • ATP is synthesized in the matrix from ADP and inorganic phosphate.

  • Other proteins utilize the proton gradient for transport of ADP and phosphate into the matrix.

Glycolysis and Citric Acid Cycle Yield

• Glycolysis Products: 2 ATP, 2 NADH (yielding 5 ATP).

• Pyruvate to Acetyl CoA:

  • Produces 2 NADH (5 ATP) and transports pyruvate into mitochondria.

• Citric Acid Cycle Output:

  • Results in 6 NADH (15 ATP), 2 ATP, and 2 GTP (also contributing 2 ATP).

• Total ATP Calculation: Total of 30 ATP, despite potential maximum being higher.

Cell Regulation and Cancer Biology

• Nucleic Acids Introduction: Discussing importance in cancer biology.

• Cell Division Regulation:

  • Normal cell division: tightly regulated.

  • Cancerous cells: Lose regulation, leading to uncontrolled growth.

Cell Cycle Control System

• Normal Behavior: Cells divide only when instructed by the cell cycle control system.

• Mutations and Regulation: Mutations can disrupt normal signaling pathways, leading to cancer.

Insights into Cancer Biology

• Mutations Accumulation:

  • Results in increased cell division, potentially creating tumors that can metastasize.

• Important Processes: Understanding normal cellular processes before studying cancerous changes.

Molecular Level Insights: Nucleic Acids

• Central Dogma Recap:

  • DNA -> RNA -> Protein, focusing on how mutations in DNA alter protein functions.

• Types of Mutations:

  • Silent Mutation: Change in DNA sequence that does not affect the protein.

  • Nonsense Mutation: Introduces a stop codon leading to a nonfunctional protein.

  • Missense Mutation: Change in amino acid sequence affecting protein function.

DNA Structure and Replication

• Nucleotides Composition: Phosphate, sugar, and nitrogenous base (difference between RNA and DNA).

• Base Pairing Rules:

  • Purines (A, G) pair with Pyrimidines (C, T, U), maintaining DNA structure stability.

Chromatin Structure and Gene Regulation

• Packaging of DNA:

  • DNA is tightly packed in chromosomes using histone proteins (nucleosomes).

• Transcription Regulation:

  • Chromatin structure impacts transcription ability, affecting gene expression.

• Chromatin Types:

  • Heterochromatin: Tightly packed, not transcribed.

  • Euchromatin: Loosely packed, allows transcription.

Summary and Next Steps

• Upcoming Topics:

  • Discussions on DNA replication and cell division.

• Importance of Study: Link between nucleic acids and cancer biology highlights the relevance of molecular understanding in cellular functions.

Lab Updates and Assignments

Dai Amalan's Experiment

• Focus: Two groups returning today for data analysis and further discussion on results. Each group is expected to present their findings and methodologies employed during the experiment.

Lab Report

• Due Date: Sunday

• Requirements: A formal lab report detailing the experiment's purpose, hypotheses, methodology, results, and discussions must be submitted. Specific formatting and content guidelines are available on Canvas to aid in the structuring of the report.

Assignments

• Perusal Assignments:

  • First Assignment: Analyzing the structure of nucleic acid was due last night. Ensure you have submitted this through the designated portal.

  • Second Assignment: Upcoming assignment due on Tuesday night, which focuses on the intricacies of DNA replication. This includes understanding the replication fork and the roles of various enzymes involved in the process.

Exam Reminder

• Exam 5 Schedule: One week from today.

• Topics Covered:

  • Citric Acid Cycle: Understand the series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetate derived from carbohydrates, fats, and proteins.

  • Oxidative Phosphorylation: Comprehend the process of ATP generation in mitochondria, involving the electron transport chain and chemiosmosis.

  • Structure of Nucleic Acid: Familiarize yourself with the molecular composition and functional groups present in Nucleic acid.

  • DNA Replication: An in-depth understanding of the mechanisms and significance of accurate DNA duplication prior to cell division.

  • Cellular Respiration Overview: Comprehensive overview of how cells convert biochemical energy from nutrients into ATP and eliminate waste products.

  • Oxidative Phosphorylation & Electron Transport Chain: Investigate how electrons are transferred along the chain and the implications on ATP synthesis.

Role of ATP Synthase

• Functionality: ATP synthase is a crucial enzyme that produces ATP by utilizing the proton gradient generated during oxidative phosphorylation.

• Proton Gradient Mechanism: ATP synthase operates like a turbine; as protons flow down the gradient through the enzyme, ATP is synthesized from ADP and inorganic phosphate.

Effect of DNP (Dinitrophenol)

• Mechanism: DNP acts by inserting itself into the mitochondrial membrane, providing a pathway for protons to bypass ATP synthase which subsequently decreases overall ATP production, leading to inefficiency in energy generation.

ATP Yield Calculation

• Theoretical Maximum: In ideal situations, a cell can potentially generate up to 38 ATP molecules per glucose molecule.

• Realistic Production: In practice, due to metabolic adaptations and efficiency, typical yield is closer to 30 ATP molecules per glucose.

ATP Synthesis

• Synthesis occurs in the mitochondrial matrix, where ATP is generated from ADP and inorganic phosphate. Other transport proteins facilitate the entry of ADP and phosphate into the matrix, utilizing the proton gradient for efficient transport.

Glycolysis and Citric Acid Cycle Yield

• Glycolysis Products: Glycolysis results in net production of 2 ATP and 2 NADH, contributing a total yield of approximately 5 ATP.

• Pyruvate Conversion: The transition from pyruvate to Acetyl CoA generates 2 NADH (5 ATP contribution) while transporting pyruvate into the mitochondria for further oxidation.

• Citric Acid Cycle Output: This cycle produces 6 NADH (15 ATP), 2 ATP, and 2 GTP, contributing an additional 2 ATP towards overall ATP yield.

• Total ATP Calculation: Upon analyzing the processes, the total ATP yield reaches around 30 ATP, despite the potential maximum being higher due to real-world biological conditions.

Cell Regulation and Cancer Biology

• Nucleic Acids Introduction: This section highlights the critical role of nucleic acids in cancer biology, the genetic basis of cancer, and how altered nucleic acid functionality can contribute to tumorigenesis.

• Cell Division Regulation: Under normal physiological conditions, cell division is tightly regulated to maintain tissue homeostasis. In contrast, cancerous cells lose this regulation, leading to uncontrolled growth and proliferation.

Cell Cycle Control System

• Normal Behavior: Cells typically undergo division only when signaled appropriately by the cell cycle control system, which includes checkpoints to prevent errors in division.

• Mutations and Regulation: Genetic mutations can disrupt these signaling pathways, resulting in aberrant cell behaviors characteristic of cancer.

Insights into Cancer Biology

• Mutations Accumulation: Over time, mutations may accumulate, leading to increased rates of cell division and potentially initiating tumor development. Understanding these processes is crucial for cancer treatment and prevention strategies.

Important Processes

• Understanding Normal Cellular Processes: Gaining insight into standard cellular mechanisms is essential before delving into the alterations that occur in cancerous tissues to develop effective interventions.

Molecular Level Insights: Nucleic Acids

• Central Dogma Recap: The flow of genetic information from DNA to RNA to protein is vital, with emphasis on how mutations in DNA sequences can impact protein functionality and overall cellular physiology.

• Types of Mutations Explained:

  • Silent Mutation: A mutation that causes a change in DNA sequence without altering the protein's amino acid sequence or function.

  • Nonsense Mutation: Results in a premature stop codon, leading to truncated and usually nonfunctional proteins.

  • Missense Mutation: Causes substitution of one amino acid for another, potentially altering protein function or leading to maladaptive outcomes.

DNA Structure and Replication

• Nucleotides Composition: DNA and RNA are composed of nucleotides containing a phosphate group, sugar, and a nitrogenous base. The structural differences (like the absence of uracil in DNA) are crucial for their diverse roles in genetic information storage and transfer.

• Base Pairing Rules: The pairing between purines (adenine, guanine) and pyrimidines (cytosine, thymine, uracil) is vital for maintaining the stability and integrity of the DNA double helix.

Chromatin Structure and Gene Regulation

• Packaging of DNA: DNA is organized into complex structures called chromatin, which is tightly coiled around histone proteins to form nucleosomes; this packing is essential for DNA compaction within the nucleus and impacts gene expression.

• Transcription Regulation: The structure of chromatin affects the ability to transcribe specific genes, regulating gene expression levels based on cellular conditions and signaling.

  • Chromatin Types:

    • Heterochromatin: Condensed structure that is generally transcriptionally silent and not actively involved in gene expression.

    • Euchromatin: Loosely packed chromatin that is accessible for transcription, facilitating gene expression.

Summary and Next Steps

• Upcoming Topics: Prepare for in-depth discussions on DNA replication mechanisms and the regulatory aspects of cell division in the next class.

• Importance of Study: Understanding the link between nucleic acids and cancer biology is crucial, as molecular insights guide the development of targeted therapeutic interventions and enhance knowledge of cellular functions.