A brief description of Oxidative phosphorylation, not too detailed, but should work for majority.

1. OXIDATIVE
PHOSPHYLATION
Raja Mohamed

2. OXIDATIVE
PHOSPHYLATION
 A combination of ETC & Chemiosmosis
 The process involves flow of electrons
through the Electron Transport Chain,
generating energy utilised to pump Protons
from Matrix into IMS – building an
Electrochemical gradient
 ATP SYNTHASE transports the protons back
into the matrix & uses the energy generate
by the flow of protons to phosphorylate ADP
into ATP.
o ELECTRON TRANSPORT-LINKED PHOSPHORYLATION.

3. COMPLEX I
o NADH-UBIQUINONE OXIDOREDUCTASE
o NADH DEHYDROGENASE
NADH is oxidized to NAD+
Flavin mononucleotide to FMNH2
FMNH2 to an Fe-S cluster
Fe-S cluster to Ubiquinone (Q)
• NADH donates it’s electron
• Electrons are first received by flavin
mononucleotide, bound to hydrophilic arm.
• Ferrous (FE2+) to Ferric state (FE3+)
 4 Protons are translocated from the
mitochondrial matrix to the intermembrane
space.
• L - shaped
• 2 Arms;
i. Hydrophobic Arm in IMM
ii. Hydrophilic Arm in MATRIX

4. • Ubiquinol moves through the hydrophobic
region of the membrane by diffusion to
complex 3
• The electron is transferred to a protein
complex, known as Cytochrome Reductase.
COENZYME Q
o UBIQUINONE
• An organic molecule dissolved in the
hydrophobic region of the inner membrane
of Mitochondrion.
• Freely permeable within the hydrophobic
region of the membrane, by diffusion.
• Accepts an electron & combines with 2H+
from matrix and gets converted into reduced
form.
Fe-S cluster to Ubiquinone
Ubiquinone to Ubiquinol
Ubiquinol to cytochrome c1

5. COMPLEX II
o SUCCINATE-UBIQUINONE OXIDOREDUCTASE
o SUCCINATE DEHYDROGENASE
• Complex II has a electron transport pathway
parallel to Complex I
• Removes hydrogen from Succinate & oxidise it to
Fumarate in the Kreb Cycle & FADH2 is produced
 Complex 2 cant pump protons
FADH2 to an Fe-S cluster
Fe-S cluster to Ubiquinone (Q)
• Ferrous (FE2+) to Ferric state (FE3+)
• Ubiquinone is a common electron
acceptor for complex I & II

6. o UBIQUINOL-CYTOCHROME C OXIDOREDUCTASE
o CYTOCHROME BC1 COMPLEX
COMPLEX III
Ubiquinol to an Fe-S cluster
Fe-S cluster to Cytochrome b
Cytochrome b to Cytochrome c1
Cytochrome c1 to Cytochrome c
• 2e- are removed from QH2 at the QO site
 4 Protons are translocated from the
mitochondrial matrix to the intermembrane
space.

7. CYTOCHROME C • Soluble Heme containing protein
• Mobile electron carrier loosely associated with
the inner membrane
• The Heme group of cytochrome c accepts
electrons.
• It’s capable of carrying 1e- at a time.
Cytochrome c1 to Cytochrome c
Cytochrome c to CuA
• 2e- are transferred to 2 molecules of CYT c
o CYT C
• 4e- are removed from 4 molecules of CYT c

8. o CYTOCHROME C OXIDASE
COMPLEX IV • The complex
contains:
• 2 Heme groups
i. Cytochrome a
ii. Cytochrome a3
Cytochrome c to CuA
CuA to Cytochrome a
Cytochrome a to CuB
CuB to Cytochrome a3
Cytochrome a3 to O2
• final electron acceptor is O2, gets
reduced into 2 H2O & this causes
pumping of 4H+
 2H+ are translocated from the mitochondrial
matrix to the intermembrane space.
• 2 Copper centres
i. CuA
ii. Cub

9. o ATP SYNTHASE
COMPLEX V
• Catalyzes ATP synthesis utilizing energy
generated as protons flow through ATP
synthase.
• ATP synthase has 2 domains;
 F0
• Integral membrane protein complex.
• provides a channel for the translocation of
protons across the membrane
• Subunits
 A
 C
 F1
• Peripheral complex bound to the inner
mitochondrial membrane
• contains the binding sites for ATP and ADP and
catalyzes ATP synthesis
• Subunits
 α
 β
 ɣ
 δ
 ε
Binding sites

10. Intermembrane space to A – subunit
A – subunit to c – subunit
C – ring rotates
C – subunit to matrix
ɣ rotates
 Change in conformation of α3β3
hexamer ring.
 3 States
O STATE
T state
L STATE
structure is constrained & the reactants
are brought close enough to form ATP
formed ATP can be release & binds ADP & Pi
reactants
ADP & Pi are trapped & cant escape
F0 DOMAIN F1 DOMAIN

11. DEFECTS
 Defects of oxidative phosphorylation usually results
from alteration in mtDNA
 Tissues with greater ATP requirement are most
affected
• CNS
• Skeletal Muscle
• Cardiac Muscle
 When mitochondrial ATP synthesis has been
compromised by a mitochondrial defect,
secondary lesions may be generated by changes
in mitochondrial protein synthesis, increased
matrix CoA and resulting in Carnitine Deficiency,
decrease in Krebs cycle intermediates and
increased free radical formation leading to cell
death.
Mutation in Mitochondrial DNA
• Mitochondrial myopathies
• Leber’s hereditary optic neuropathy
• Kidney
• Liver

12. THANK YOU
Rajamd_
Rajamd7