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MCB 150: The Molecular and Cellular Basis of Life

Lecture 11: Cellular Respiration

Announcements:

• No lecture or student hours on Friday of this week.

• Pre- and post-class questions will be assigned as usual.

• Lecture recording from Fall 2024 will be utilized for content review.

• Times to review exam questions (200 Burrill Hall):

  • Today: 3:30-5:00 PM

  • Tuesday: 10:30-Noon

  • Thursday: 9:30-11:00 AM

Phase 2: Pyruvate Oxidation and Krebs Cycle

• Net Results for Every Glucose:

  • Glycolysis, the first step in glucose metabolism, produces pyruvate.

  • Pyruvate oxidation and the Krebs Cycle yield crucial metabolic products: CO2 (carbon dioxide), NADH, and FADH2 (flavin adenine dinucleotide).

• Problems at the end of Krebs Cycle:

  • The coenzyme NAD+ must be replenished, as it is reduced to NADH. Thus, more NADH accumulates.

  • FADH2 also requires re-oxidation to continue accepting electrons.

  • Energy carried by cofactors like NADH and FADH2 must be transferred to synthesize ATP (adenosine triphosphate).

Oxygen Dependency:

• While the Krebs Cycle itself does not directly require oxygen, it is tightly coupled to the Electron Transport Chain (ETC), which is an oxygen-dependent process essential for energy production.

Oxidative Phosphorylation: Electron Transport Chain

• Key Processes:

  • NADH donates electrons to the first electron carrier in the ETC. As electrons pass through various carriers sequentially, they release energy.

  • This energy is utilized to pump protons (H+) across the mitochondrial membrane, creating a proton gradient that is critical for ATP synthesis.

  • The final electron carrier transfers electrons to molecular oxygen, resulting in the formation of water and completing the electron transport cycle.

  • FADH2 contributes electrons at a later step in the chain, resulting in fewer protons being pumped across the membrane, leading to a lower ATP yield per FADH2 molecule than NADH.

Result of Electron Transport Chain

• The ETC generates a proton gradient across the mitochondrial membrane; however, it does not directly produce ATP. Instead, the potential energy stored in the gradient is used for ATP synthesis during chemiosmosis.

Energy Levels of Electron Carriers:

• The energy levels of the electron carriers can be visualized in diagrams that illustrate the concentration and electrical potential gradients established across the membrane during the ETC.

Theoretical ATP Production from Complete Oxidation of Glucose

• The breakdown of glucose yields a potential total of 36 ATP molecules from one glucose molecule, calculated as follows:

  • Glycolysis: 2 ATP directly + 4 ATP through 2 NADH (2 NADH x 2 ATP each)

  • Krebs Cycle: 2 GTP (equivalent to ATP) + 24 ATP from 8 NADH (8 NADH x 3 ATP each) + 4 ATP from 2 FADH2 (2 FADH2 x 2 ATP each)

  • Total Theoretical ATP per Glucose: 36 ATP

Lecture 12: Fermentation and Regulation of Metabolism

Announcements:

• Student hours today from 4:00-5:30 PM.

• One-on-one conversations to clarify any concepts and reminders regarding no lecture on Friday are available.

Fermentation: Pathways for ATP Production Under Anaerobic Conditions

• In anaerobic conditions, glycolysis occurs, but the Krebs Cycle and oxidative phosphorylation do not take place, thereby limiting ATP production.

• Fermentation Mechanics:

  • Fermentation converts pyruvate into different end products to regenerate NAD+, allowing glycolysis to continue despite the absence of oxygen.

  • While it does allow for continued ATP generation through glycolysis, fermentation yields no additional ATP per glucose compared to aerobic respiration but increases the rate of glycolysis.

Types of Fermentation:

• In Yeast: Pyruvate is converted to Ethanol + CO2, which is utilized in the production of alcoholic beverages.

• In Muscle Cells: Pyruvate is reduced to Lactic Acid, which can lead to muscle fatigue during intense exercise when oxygen supply is limited.

Regulation of Catabolic and Biosynthetic Pathways

• The primary goals are to minimize unnecessary energy expenditure and coordinate the metabolic processes through the regulation of enzyme amounts and activity levels.

• Allosteric Regulation:

  • Regulatory molecules bind to sites other than the enzyme's active site, leading to conformational changes that can either increase or decrease the activity of the enzyme.

  • Positive regulators increase enzyme activity, while negative regulators decrease activity.

  • Feedback inhibition serves as a mechanism that regularizes the flow through metabolic pathways.

  • Feedback Inhibition Example: ADP or AMP binding increases the activity of Phosphofructokinase (PFK), while ATP binding reduces its activity, showcasing allosteric regulation's impact on glycolytic efficiency.

Additional Concepts in Transcription and DNA Replication

Central Dogma of Molecular Biology:

• The process of molecular biology is often summarized by the central dogma: DNA → RNA → Protein, illustrating the flow of genetic information.

Transcription Steps in E. coli:

1. Promoter Recognition: RNA polymerase binds to the promoter region of the gene.

2. Initiation: Transcription begins with the synthesis of RNA complementary to the DNA template.

3. Elongation: The RNA strand elongates, synthesizing a complementary RNA molecule.

4. Termination: Transcription stops when RNA polymerase reaches a termination signal.

• Involvement of RNA Polymerase: The holoenzyme form of RNA polymerase initiates transcription by recognizing specific promoter regions on the DNA.

Important Terminology in DNA Processes:

• Enzyme Types:

  • Primase: Adds RNA primers necessary for DNA polymerase to begin synthesis.

  • Ligase: Seals gaps and nicks between DNA fragments, ensuring complete DNA strands.

  • Nucleases: Enzymes responsible for degrading nucleic acids, playing a role in DNA repair and replication.

Chromatin Structure and Organization

• Histones: Basic proteins that compact DNA into structural units called nucleosomes.

• Nucleosome and Chromatosome Definitions:

  • Nucleosome: A unit of DNA consisting of 146-147 base pairs wrapped around a histone core, fundamental for DNA packaging.

  • Chromatosome: A nucleosome that includes an additional histone protein (H1), further stabilizing the structure.

• DNA Packing:

  • In eukaryotic cells, nucleosomes compact DNA to facilitate efficient packaging within the nucleus, while higher-order structures, like the 30-nm fiber, enable further condensation.

Summary of DNA Replication

• The DNA replication mechanism follows the semiconservative model, where each resulting daughter helix consists of one original (parent) strand and one newly-synthesized strand.

• DNA replication requires specific enzymes and nucleotide precursors for efficient synthesis, and it is critical for cell division and inheritance.