•Enzyme complexes in the ETC
•Structure of ATP synthase
•Oxidation of 1 NADH = 10 H+ = 2.5 ATP/NADH molecule. - not
•4H : 1 ATP
Complex I: NADH-CoQ Oxidoreductase
Catalyzes oxidation of NADH coupled to the reduction of CoQ
•This is the largest protein complex in the mitochondrial membrane,
•Contains 46 subunits with 10 redox centers:
•1 FMN and 9 Fe-S clusters.
•FMN becomes FMNH upon N2DH reduction
•Electrons pass between centers in a stepwise fashion. Oxidative Phosphorylation
•NADH donates two electrons.
•Cytochrome c can accept only one electron.
•CoQ can transfer one or two electrons.
Electron transfer between the 10 redox centers is coupled to 4 proton pumps
which pump H+ out of the matrix. The detailed mechanism remains unknown.
Complex II: Succinate-CoQ Oxidoreductase
This complex contains succinate dehydrogenase, the only membrane-bound enzyme
of the citric acid cycle, along with 3 other hydrophobic subunits.
•The complex contains ﬁve redox centers:
•1 FMN - Flavin Mononucleotide
•3 Fe-S clusters
•Electrons move from succinate to FADH and 2hen, through Fe-S clusters and
cytochrome b, to CoQ.
•CoQ moves freely within the lipid bilayer. It collects electrons from complexes I and II
and transfers them to complex III.
Complex III:CoQ-Cytochromec Oxidoreductase
This complex passes electrons from the reduced CoQ to cytochrome c.
•The contex contains four redox centers:
•2 cytochrome b
•1 cytochrome c
•1 Fe-S cluster
•Cytochrome c is a peripheral membrane protein. It carries electrons in the
intermembrane space from Complex III to complex IV. Oxidative Phosphorylation
Complex IV: Cytochrome c Oxidase
Cytochrome c oxidase catalyzes the overall reaction
•Contains four redox centers
•Coupled to the pumping of 2 protons from the matrix to the intermembrane space.\
•Oxidation of NADH in the ETC results in the expelling of 10 protons from the matrix to
the intermembrane space. The obtained proton gradient is used as a driving force in
the endergonic reaction of ATP synthesis. Oxidative Phosphorylation
Chemiosmotic Theory: The free energy of electron transport is conserved by pumping
H+ from the matrix to the intermembrane space. The obtained electrochemical potential
drives ATP synthesis.
•Proposed in 1961 by Peter Mitchel to explain the following observations:
! Chemiosmotic Theory: ions do not permeate via an intact inner mitochondrial
membrane. ATP synthesis is blocked by increasing
permeability of the inner mitochondrial membrane for ions
and protons. Oxidation of NADH creates an electrochemical
gradient across the inner membrane. ATP synthesis is thus
stimulated by increasing cytosolic [H+]. Oxidative Phosphorylation
ATP Synthase: Free energy in expelling one proton from the matrix (21.5kJ/mol) is less
than that required to synthesize one ATP molecule from ADP and Pi (>40kJ/mol).
•ATP synthase catalyzes the endergonic synthesis of ATP by coupling it to the
exergonic ﬂow of protons to the matrix. Downhill movement of 3 protons to the matrix
releases energy necessary to synthesize 1 ATP molecule.
•3 H+ in = 1 ATP out.
•Multisubunit protein composed of 2 functional parts
•ransmembrane proton channel:
•ater-soluble peripheral membrane protein:
•Compounds that block proton permeation through the channel (oligomycin B) inhibit
CELLULARRMEETABOLISM FOR 1MOOLECULEEOF GLUCOOSE
STEP ELECTRON CARRIERS PRODUCTS
Glycolysis 2 NADH produced 2 ATP (4total-2consumed) Oxidative Phosphorylation