Electron Transport and the Respiratory Chain

Learning Goals:
1. Electron flow is coupled to creation of charge and chemical gradient across the mitochondrial inner membrane. Energy is
stored in the proton gradient.
2. Learn order of major electron carriers within the electron transport chain.
3. Become familiar with redox carriers and interactions.

I. The BIG Picture

a. Most of the energy released from glucose (glycolysis, oxidation of pyruvate) is captured as NADH and FADH2.
(Same along with catabolism of fatty acids) WHAT THE CELL REALLY NEEDS IS ATP.
b. Electron transport + oxidative phosphorylation allows NADH/FADH2  ATP.
i. Electrons released from NADH/FADH2, flow through electron transport chain  reduce O2 to H2O
ii. Flow from one carrier to next down energy gradient: work = pumping H+ out of mitochondrial matrix
iii. Energy of NADH/FADH2 = proton gradient
c. Protons flow back in  synthesize ATP from ADP and Pi
II. Structure of mitochondria
a. Electron transport carriers, ATP synthesizing unit: embedded in inner membrane (impermeable to charged species)
b. Metabolite transporters, NADH Shuttles
i. Reducing equivalents of NADH generated in the cytosol must be delivered to the matrix
1. Glycerol phosphate shuttle: irreversible, yields FADH2  reduced CoQ, active in skeletal
muscle/brain
2. Malate-aspartate shuttle: irreversible, reforms NADH, active in liver/heart (cytosolic NADH does
not enter mitochondrial matrix- 2 electrons ride in on malate, make a new NADH)
III. Electron carriers
a. NADH and FADH2
i. NAD can only be reduced in a 2 electron fashion, FAD and FMN can accept 1 or 2 electrons
b. Ubiquinone (Coenzyme Q)
i. Lipid-soluble electron carrier (long hydrophobic tail), part of Complex 1 and freely mobile inside the
mitochondrial inner membrane
ii. Can accept 1 or 2 electrons
iii. Iron sulfur clusters
c. Cytochromes
i. Occur in ALL complexes (differ in side chains)
ii. Cytochrome c slides along the outer surface of the mitochondrial inner membrane: carries electrons
between Complex III and IV
iii. Small proteins with heme groups bound
IV. Overview of Electron Transport/Oxidative Phosphorylation
a. Couple highly exergonic reaction (NADH oxidation by O2) to a highly energonic reaction (ATP synthesis from
ADP and Pi)
b. Transfer of electrons is indirect, passing through numerous electron carriers organized into three complexes (I, III,
IV)  energy released used to pump protons out of the mitochondrial matrix
c. Protons flow back into matrix (negative ΔG=favorable) used to synthesize ATP
d. Relation between reduction potential difference and free energy change
e. Mitochondrial electron flow
i. Electron pair from NADH  complex I  ubiquinone (4 H+ pumped from matrix to intermembrane
space)
ii. Ubiquinone  complex II (2 H+ pumped)
iii. Complex II  Cyt c  complex IV (4 H+ pumped and ½ O2 reduced to H2O for each pair of electrons
that arrive)
iv. Some protons are pumped by being released from CoQH2 into the inter-membrane space, some are
consumed in the matrix and some are just pumped out
V. Effect of substrate and O2 availability and of the need for ATP on electron flow
a. Electron flow is tightly coupled to proton pumping (proton gradient large  not enough energy available for
electrons to flow, flow stop until gradient diminished- make ATP, wasted)
VI. Defects and Poisons of the respiratory chain
a. Complex III partial deficiency  myopathy, muscle weakness, lactic acidosis (lower phosphocreatine initially,
takes longer to restore after exercise.)
b. Poisons: cyanide, carbon monoxide, nitric oxide  inhibits complex IV reversibly, destroys FeS centers of
complexes I and II