Electron Transport Chain (ETC) Review

Electron Transport Chain (ETC) Discussion

• The electron transport system (ETC) is a sequence of protein complexes located in the inner membrane of the mitochondria.

• It plays a critical role in cellular respiration by generating ATP and water from ADP and inorganic phosphate (P) through redox reactions.

Overview of Mitochondrial Structure

• Mitochondrion Components:

  • Outer Membrane

  • Intermembrane Space

  • Inner Membrane

  • Mitochondrial Matrix

Major Components of the ETC

• **Electron Carriers: **

  • NADH (Nicotinamide adenine dinucleotide, reduced form)

  • FADH2 (Flavin adenine dinucleotide, reduced form)

Sequence of Events in Cellular Respiration

• Glucose is converted through several steps:

  • 2 Glucose → 2 Pyruvate

  • 2 Pyruvate → 2 Acetyl-CoA (Link Reaction)

  • Produces:

  • 2 x (3 NADH + 1 FADH2 + 1 ATP + 2 CO2)

  • Resulting in approximately 36 ATP + H2O + Regenerated NAD+ & FAD

• The major purpose of this pathway is to convert the energy of electron carriers (NADH/FADH2) to generate ATP.

Final Electron Acceptor

• The ETC transfers electrons from NADH and FADH2 to oxygen, the final electron receptor, through a series of complexes, resulting in the formation of water.

Structure and Function of Complexes in ETC

Complex I - NADH Dehydrogenase

• Accepts electrons from NADH derived from the Krebs cycle.

• Passes electrons to ubiquinone (CoQ).

• Pumps 4 protons (H+) into the intermembrane space.

• Process:

  • NADH transfers 2 electrons (e-) to FMN (Flavin mononucleotide), regenerating NAD+ and H+.

  • Electrons are then moved through sulfur clusters within the complex.

Complex II - Succinate Dehydrogenase

• Accepts electrons from FADH2 (from the Krebs cycle).

• Passes electrons to ubiquinone (CoQ).

• Does not pump protons into the intermembrane space.

Ubiquinone (CoQ)

• Accepts electrons from Complex I and Complex II.

• Transfers electrons to Complex III.

Complex III - Cytochrome bc1 Complex

• Accepts electrons from ubiquinone (CoQ).

• Passes electrons to cytochrome c.

• Pumps 4 protons (H+) into the inner membrane space.

Cytochrome C

• Transfers electrons from Complex III to Complex IV.

Complex IV - Cytochrome c Oxidase

• Accepts electrons from cytochrome c.

• Passes electrons to molecular oxygen, leading to the formation of water:

  • Reaction: 2H + O + 2e → H2O (occurs twice)

• Pumps 2 protons (H+) into the intermembrane space.

Final Step: ATP Synthesis via ATP Synthase (Complex V)

• FoF1 Complex (ATP Synthase):

  • Fo portion: Embedded in the membrane to form a channel.

  • F1 portion: Faces the matrix and spins to produce ATP.

• ATP Synthase uses the proton gradient generated by the ETC to allow protons to flow back into the mitochondrial matrix. This energy is harnessed to convert ADP and inorganic phosphate (P) into ATP.

Variation in ATP Yield: 36 vs. 38 ATP

• NADH from glycolysis cannot enter mitochondria directly; its electrons are transferred by two shuttle systems:

1. Malate–Aspartate Shuttle

• More efficient; yields 3 ATP per NADH.

• Overall yield: approximately 38 ATP total.

• Electrons are passed to Complex I of the ETC, resulting in proton pumping as expected.

  • Process:

  • Oxaloacetate is converted to malate (cannot cross mitochondrial membrane) and this conversion also regenerates NAD+.

  • After entering, malate is converted back to oxaloacetate, regenerating NADH.

2. Glycerol-3-Phosphate Shuttle

• Less efficient; yields only 2 ATP per NADH, leading to approximately 36 ATP total.

• NADH in the cytoplasm donates electrons to dihydroxyacetone phosphate, forming glycerol-3-phosphate (G3P), which interacts with an enzyme passing electrons to FAD.

• FADH2 is formed and instead of passing electrons to Complex I, it donates electrons to ubiquinone, causing a loss of proton pumping and resultant ATP.

Proton Motive Force (PMF)

• The proton motive force is the electrochemical energy stored when protons (H+ ions) are pumped across a membrane.

• Formula for PMF:
  pmf = V_m + \frac{2.303 R T \Delta pH}{F}

• Where:

  • Vm: membrane potential (in Volts)

  • ΔpH: pH gradient = pHmatrix – pHcytosol

  • R: gas constant (1.987 cal/mol•K)

  • T: temperature (in Kelvin, where T = °C + 273)

  • F: Faraday’s constant (23,062 cal/mol; equals 96485 C/mol)

Average Mitochondrion Conditions for PMF Calculation

• Conditions:

  • Temperature: 37ºC

  • Membrane potential (Vm): 0.16 V

  • ΔpH: 1.0

• Calculation of PMF:
  pmf = 0.16 + \frac{2.303 (1.987)(310)(1.0)}{23062}
  pmf = 0.22 ext{ Volts}

Importance of PMF in ATP Synthesis

• With an average PMF of 0.22 Volts, ATP synthesis requires approximately 3 to 4 protons to generate one molecule of ATP.