Biology lecture 11 (Chapter 5)

BI110 Lecture 11 - October 23

• Lecture date: Wednesday, October 23
• Instructor: Dr. Leonard
• Reminders: SI sessions on Sunday, Monday and Wednesday

Reminders

• Today's lecture: Review of Chapter 4 (Cell Membranes and Signalling) and introduction to Chapter 5
• Chapter 4 Mindtap Assignment due: Sunday, October 27th, at 11:59 PM
• Midterm #2: Wednesday, November 20th, during class

Signal Transduction Pathways

• Binding a signal molecule to a plasma membrane receptor triggers a signalling cascade.
• The signal molecule does not enter the cell.
• Molecules similar to the signal molecule can either trigger or block a cellular response if able to bind to the receptor's recognition site.
• Drug treatments often target signal transduction pathways, sometimes at the receptor level.

Signal Transduction Pathways (continued)

• Cells often use protein kinases to relay signals.
• Protein kinases transfer phosphate groups from ATP to target proteins.
• Added phosphate groups can stimulate or inhibit target protein activity.
• Protein phosphatases reverse the effects of kinases by removing phosphate groups from target proteins, keeping them continuously active.
• Some signal cascades include second messengers like cAMP.

Phosphorylation

• Protein kinases often act in a chain, creating a phosphorylation cascade.
• Each kinase in the cascade phosphorylates the next, culminating in a target protein.
• Target protein phosphorylation affects activity, thus impacting the cellular response.

Phosphorylation Cascade (Figure 4.24)

• Process starts with the signal binding to a receptor.
• Receptor activates protein kinase 1.
• Protein kinase 1 activates protein kinase 2.
• Protein kinase 2, in turn, activates a target protein, creating a cellular response

Amplification (Figure 4.25)

• Amplification increases the magnitude of each stage during a signal transduction pathway.
• Each activated enzyme can activate hundreds of other proteins (enzymes) in the next stage of the pathway.
• More enzyme steps in a pathway correlate to a greater degree of amplification of the response.
• A few external signal molecules binding to receptors can result in a full internal response.

Example: Stimulation of Glycogen Breakdown (Epinephrine Pathway)

• The Nobel Prize-winning researcher Sutherland discovered the role of epinephrine in blood glucose increase.
• Epinephrine is a hormone secreted from the adrenal gland
• It's the first messenger.
• It initiates the process of glycogen breakdown, raising blood glucose levels.
• Hormone binding triggers secondary messenger production.
• Kinases phosphorylate, activating enzymes to stimulate glycogen breakdown.

Adrenaline Responses

• The "fight or flight" response (caused by adrenaline) causes various physiological changes.
• These changes include a burst of glucose energy release into the bloodstream, increased heart rate, and dilated pupils.
• Longer-term responses may involve the expression of specific genes in different cell types.

Chapter 5

• Introduces topics relating to oxidation-reduction reactions.

Oxidation-Reduction (Redox) Reactions

• Electron transfer reactions between atoms or molecules.
• Oxidation: loss of electrons
• Reduction: gain of electrons
• LEO the lion says GER (Loss of Electrons is Oxidation)

Electron Sharing

• Redox reactions can involve partial electron sharing changes in covalent bonds.
• For example, methane (CH4) burning demonstrates relative electron sharing shifts.
• Oxygen gains a larger share of electrons relative to carbon.

Oxidation

• Partial or complete electron loss.
• The electron donor is oxidized.
• Example: Glucose oxidation to carbon dioxide.

Reduction

• Partial or complete electron gain.
• The electron acceptor is reduced.
• Example: Oxygen reduction to water.

A Redox Reaction

• Oxidation and reduction occur concurrently, or as coupled reactions.

Combustion and Cellular Respiration (Figure 5.4)

• Cellular respiration is a controlled combustion process.
• Energy released is transferred to carrier molecules, preventing excessive heat gain.
• Energy is released from glucose through a stepwise process to maintain a manageable degree of temperature increase.

Electron Carrier NAD+ (Figure 5.5)

• NAD+ is the oxidized form of an electron carrier involved in redox reactions
• Two electrons and a hydrogen ion bind to NAD+ to produce NADH.

Oxidation-Reduction Reactions (Continued)

• Reduction of NAD+, to NADH and FAD to FADH2.
• Reverse to oxidize NADH to NAD+ and the FADH2 to FAD.

Cellular Respiration

• C6H12O6 + 6O2 → 6CO2 + 6H2O + energy
• Glucose + Oxygen → Carbon dioxide + Water + Energy

Cellular Respiration: Three Stages (Figure 5.6)

• Glycolosis (cytosol): Glucose is broken down into pyruvate.
• Pyruvate oxidation and the citric acid cycle (mitochondria): Pyruvate is oxidized to acetyl CoA and enters the citric acid cycle.
• Oxidative phosphorylation (mitochondria): Electrons are transferred through the electron transport chain to produce ATP.

Mitochondria

• Major site of cellular respiration.
• Reactions carried out in mitochondria´s: Inner mitochondrial membrane and matrix.

Reactions of Glycolysis (Figure 5.9)

• Glycolysis is a universal and ancient process in all cells.
• It takes place in the cytosol of the cell.
• The process involves a series of steps catalyzed by enzymes, and can be separated into two phases; the energy investment phase and the energy payoff phase.
• Glucose is converted into two molecules of pyruvate.

Glycolysis Summary

• Glycolysis does not require oxygen.
• Ten chemical reactions produce pyruvate from glucose.
• Two different phases: energy investment and energy payoff phases.

ATP molecules

• Produced in glycolysis
• Result of substrate-level phosphorylation.

Substrate-level Phosphorylation (Figure 5.10)

• Phosphate from high-energy donor to ADP.
• Forming ATP via enzyme-catalyzed reaction.

Cellular Respiration: Catabolism

• Carbohydrates are broken down into simpler molecules like CO2.
• ATP and electron carriers like NADH and FADH2 are generated.

Pyruvate Oxidation (Figure 5.11)

• Pyruvate is converted to acetyl-CoA.
• Takes place in the mitochondrial matrix.
• Produces 2 CO2.
• Generates one NADH for each pyruvate.
• Links glycolysis to the citric acid cycle.

Pyruvate Oxidation (continued)

• Each pyruvate yields one acetyl CoA, one NADH, and one CO₂.

Citric Acid Cycle (Figure 5.12)

• Acetyl-CoA is completely oxidized to CO₂.
• Electrons are removed and passed to NAD+ and FAD.
• Producing NADH and FADH₂.
• ATP is also produced via substrate-level phosphorylation.

Citric Acid Cycle Summary

• Each acetyl-CoA cycle yields 2 CO2, 1 ATP, 3 NADH, and 1 FADH₂.

Electron Transfer System and Oxidative Phosphorylation (Figure 5.14)

• NADH and FADH₂ donate electrons to the electron transport chain (ETC)
• Electrons move through a series of proteins, releasing energy used to actively transport H+ across the mitochondrial membrane, generating a H+ gradient.
• The electrochemical gradient (proton motive force) drives ATP synthesis by ATP synthase.

Respiratory Electron Transport Chain (Figure 5.15)

• Three (3) major protein complexes are involved
• Hydrogen ions (H+) are pumped from the matrix to the intermembrane space.
• Prosthetic groups cycle between reduced and oxidized states.
• Oxygen is the electron acceptor.

Electron Transport Chain

• Electrons pass from NADH and FADH₂ to oxygen.
• The chain includes four protein complexes and two smaller shuttle carriers.

Electron Transport Chain (continued 2)

• Oxidations in the ETC generate energy utilized to pump protons (H+) from the matrix to the inner membrane space.
• Creates a proton-motive force.
• Drives ATP synthesis by ATP synthase.

Oxidative Phosphorylation and Chemiosmosis (Figure 5.16)

• ATP synthase uses energy from the proton gradient across the membrane (chemiosmosis).
• ATP synthase is a molecular motor embedded in the inner mitochondrial membrane.

Oxidative Phosphorylation

• Understanding the differentiation between the ETC, proton-motive force, chemiosmosis, ATP synthase, and oxidative phosphorylation is crucial for this section.

ATP Yield from the Oxidation of Glucose (Figure 5.18)

• Glycolysis: 2 ATP, 2 NADH
• Pyruvate oxidation: 2 NADH, 2 CO2
• Citric acid cycle: 2 ATP, 6 NADH, 2 FADH₂
• Oxidative phosphorylation: ~ 25 ATP from 10 NADH, ~ 3 ATP from 2 FADH₂
• Total energy yield from glucose oxidation: 30-32 ATP

Major Pathways Oxidizing Carbohydrates, Fats, and Proteins (Figure 5.19)

• Diverse molecules (proteins, fats, carbohydrates) contribute to energy pathways.
• They enter at various points in the respiratory chain.

Respiratory Intermediates

• Glycolysis and citric acid cycle intermediates are often diverted for other biosynthetic processes.
• Provide carbon backbones for making hormones, growth factors, prosthetic groups, and other essential cofactors.

Control of Cellular Respiration (Figure 5.20)

• Various molecules regulate key steps in cellular respiration.
• Control is based on supply and demand via these regulatory molecules.

Dependence upon Presence of Oxygen

• Aerobic Respiration requires oxygen.
• Anaerobic Respiration does not use oxygen.
• Fermentation happens in the absence of oxygen.

Fermentation

• Oxidizes fuel molecules without oxygen.
• Two types exist: lactate and alcoholic fermentation.

Fermentation (continued)

• Produces ATP without the use of the ETC in anaerobic conditions.
• Pyruvate is used to produce either lactic acid or ethanol.

Lactate Fermentation (Figure 5.22a)

• Pyruvate converted to lactate.
• Electrons are transferred from NADH to pyruvate.
• Occurs in animals and bacteria
• Generates limited ATP without oxygen.

Alcoholic Fermentation (Figure 5.22b)

• Pyruvate converted to ethanol and CO2.
• Electrons are transferred from NADH to acetaldehyde.
• Occurs in plants and fungi
• Generates limited ATP without oxygen.

Anaerobic Respiration

• Some bacteria and archaea lack mitochondria but have internal membrane systems.
• Electron acceptors can be sulfate, nitrate, or ferric ion instead of oxygen for respiration.

Lifestyles Dictated by Oxygen

• Strict anaerobes cannot grow in the presence of oxygen.
• Strict aerobes require oxygen.
• Facultative aerobes can use either fermentation or respiration depending on oxygen availability.

Paradox of Aerobic Life

• While oxygen is crucial for respiration, it also creates harmful reactive oxygen species (ROS).
• ROS are strong oxidizing agents.

Reduction of Oxygen to Water (Figure 5.24)

• Oxygen reduction to water involves ROS intermediates.
• ROS are potentially harmful; need protective measures.

Defense against Reactive Oxygen Species (ROS)

• Cellular defense systems (enzymes like superoxide dismutase and catalase and non-enzymes like vitamin C and vitamin E) combat ROS.