Redox reactions in the mitochondria

Redox Reactions in the Mitochondria

Overview of Lecture

  • Lecture 17 focuses on redox reactions in mitochondria led by Dr. Amanda Barnes.

Learning Objectives

  • Electron Flow: Describe the pathway electrons take from NADH to O2 in the mitochondrial electron transport chain (ETC).

  • ATP Synthesis: Explain how electron flow energy results in ATP production via the proton motive force.

  • ATP Calculation: Calculate ATP yield from glucose and other substrates.

  • Electron Transport Disruption: Describe the effects of inhibiting electron transport complexes on ATP production.

  • Uncoupling Mechanism: Explain how uncoupling electron transport from ATP synthesis produces heat.

Cellular Respiration

  • Substrate Pathways: Different dietary substrates have specific catabolic pathways.

    • Glucose Metabolism: Glycolysis converts glucose to pyruvate, then to acetyl CoA.

    • Fatty Acid Metabolism: Fatty acids are activated and undergo β-oxidation to produce acetyl CoA.

    • Citric Acid Cycle: Acetyl CoA is oxidized to CO2, generating reduced electron carriers.

  • Reduced Electron Carriers: Key for ATP production.

Mitochondrial Functions

  • Eukaryotic Organelles: Mitochondria are double-membraned and abundant in highly respiring cells (e.g. brain, skeletal muscle).

  • Metabolic Processes: Include β-oxidation, PDH complex, citric acid cycle, and ETC. Glycolysis occurs in the cytoplasm.

  • Membrane Characteristics:

    • Outer Membrane: Permeable to small molecules/ions.

    • Inner Membrane: Impermeable to most, including H+. Has specific transporters for NADH and ATP.

Electron Transport Chain

  • Electrons to ATP: Electrons from catabolic processes produce ATP via ETC.

  • Energy and H+ Pumping: Electron carriers donate electrons to O2, driving H+ across the membrane, thus creating a potential energy difference utilized by ATP synthase.

Electron Carriers in the ETC

  • Types:

    • Ubiquinone (Q): Accepts electrons, reduced to QH2 for membrane diffusion.

    • Cytochromes (Cyt): Contain iron heme groups; carry electrons.

    • Iron-Sulphur (Fe-S) Centers: Facilitate electron transfer.

Complexes I and II of the ETC

  • Complex I:

    • Transfers electrons from NADH to ubiquinone (Q), reducing it to ubiquinol (QH2).

    • Pumps 4 H+ from matrix to intermembrane space.

  • Complex II:

    • Involves succinate dehydrogenase, oxidizing succinate and reducing Q.

    • No protons are pumped; generates less ATP than complex I.

Complexes III and IV

  • Complex III:

    • Transfers electrons from QH2 to cytochrome C, pumping 4 H+ into the intermembrane space.

  • Complex IV:

    • Transfers electrons from cytochrome C to O2, forming water; pumps 2 additional H+ into the intermembrane space.

Redox Reactions Summary

  • NADH and FADH2: Both transfer electrons through complexes with increasing reduction potential, ultimately to O2.

  • Free Energy: Used for proton pumping creating a chemiosmotic gradient.

ATP Synthesis

  • Mitochondrial ATP Synthase: Located in the inner membrane.

    • F0 Component: Integral part of the membrane, acts as a proton pore.

    • F1 Component: Catalytic part within the matrix, involved in ATP synthesis.

  • Proton Motive Force: Difference in concentration/charge of protons drives ATP formation as protons flow back into the matrix.

Rotational Catalysis in ATP Synthase

  • Mechanics: Protons enter the C ring, causing a rotation which leads to sequential conformational changes in ATP synthase, producing ATP from ADP and Pi.

Effects of Poisons on the ETC

  • Various toxins inhibit electron transport at specific complexes, disrupting electron flow and ATP synthesis (e.g., cyanide at Complex IV).

Alternative Functions of Mitochondria

  • Uncoupling Protein 1 (UCP1): Allows protons to return to the matrix without synthesizing ATP, producing heat instead.

  • Brown Adipose Tissue (BAT): Contains numerous mitochondria for heat generation in newborn mammals.

ATP Production from Glucose

  • Glycolysis produces 2 ATP directly.

  • Citric Acid Cycle produces 2 GTP and numerous reduced carriers (NADH and FADH2).

  • Total ATP from Glucose Catabolism: Approximately 32 ATP:

    • 4 from substrate-level phosphorylation, 28 from oxidative phosphorylation.

ATP Yield from NADH and FADH2

  • NADH: Yields approximately 2.5 ATP (10 H+ pumped).

  • FADH2: Yields approximately 1.5 ATP (6 H+ pumped).

Summary

  • Oxidation of NADH/FADH2: Occurs through redox reactions in the ETC, contributing to ATP synthesis.

  • Proton Gradient: Generated by electron flow, driving ATP production.

  • Inhibition and Uncoupling: Can occur through various mechanisms, affecting energy yield.

Recommended Reading

  • Nelson, D. L., and Cox, M. M. (2021). Lehninger’s Principles of Biochemistry 8th Ed. Chapters on Mitochondrial ETC and Photosynthesis.