8.OxidativePhosphorylation Complete
8.OxidativePhosphorylation Complete
8.OxidativePhosphorylation Complete
Biochemistry
Oxidative Phosphorylation
Catabolism
Catabolic pathways serve two purposes:
Breakdown of larger molecules into smaller building
units
Release and (temporary) storage of energy in high-
energy molecules
ATP/NTPs
Reduced cofactors (NADH/FADH 2)
Catabolic pathways are oxidative:
Metabolites are oxidized as cofactors are reduced.
Re-oxidation of cofactors is used to generate ATP.
Oxidative Phosphorylation
Two separate but connected processes
Oxidation of reduced cofactors (NADH, FADH2)
and reduction of molecular oxygen
NADH NAD+ + H+ + 2e-
FADH2 FAD + 2H+ + 2e-
4H+ + 4e- + O2 2H2O (or 2H+ + 2e- + ½O2 H2O)
Phosphorylation of ADP to ATP
ADP + Pi + H+ ATP + H2O
Processes are linked through a proton
gradient across the mitochondrial membrane
Overview
Reduced cofactors (NADH, FADH2) generated from glycolysis and CAC
(oxidative catabolism)
ATP synthesis
(Chemical energy)
Where does all this occur?
inter-membrane space
matrix
Complexes I - IV
(integral membrane proteins)
Cofactors in Oxidative
Phosphorylation
Multiple cofactors are reversibly
oxidized/reduced during electron transport.
Flavin mononucleotide
Iron-sulfur clusters
Prosthetic groups
Copper (Cu2+)
Cytochrome heme groups
Coenzyme Q Lipid-soluble cofactor
Fe3+ + e- Fe2+
Cytochromes are hemoproteins that carry
out electron transport.
Fe3+ + e- Fe2+
inter-membrane
space
2e-
matrix 2e-
½ O2 + 2H
+
H2O
NADH NAD+ Oxygen has a very high reduction
potential – terminal electron acceptor
Every NADH reoxidized results in 10 protons being moved out of the matrix
Reduction Potentials of Components
in the Electron Transport Chain
Increasing reduction
potential
Electron transport causes a conformational change
which allows these complexes to pump H + ions
4 H+ 2 H+
inter-membrane
space
2e-
2e-
matrix
FADH2 FAD ½ O2 + 2H+
(part of Complex II) H2O
Every FADH2 reoxidized results in 6 protons being moved out of the matrix
The Proton Electrochemical
Gradient
High pH
Negative side
Low pH
Positive side
H+ H+
H
+
H+
H+ H+
H+ H+
inter-membrane space
H+
matrix ATP
Approximately 3H+ are needed per ATP synthesized by
ATP synthase. ATP synthase
Based on this alone, approximately how many ATP are ADP + Pi
generated per NADH molecule?
ATP Synthase
Two portions
FO
Transmembrane portion
Protons pass through
Triggers conformational change in F 1
F1
Catalytic portion
Synthesis of ATP from ADP and Pi
H+ conducting
component
Matrix
H+
ADP + Pi + H+
ATP
Catalytic
component
Links
https://www.youtube.com/watch?v=3y1dO4nNaKY
https://www.youtube.com/watch?v=PjdPTY1wHdQ
https://www.youtube.com/watch?v=AigRzfNHCZA
ATP Synthase
higher pH
2e
2e-
matrix -
H2O
NADH ½ O2 + 2H+ H+
NAD+
Increase in H+ gradient
Decreased e- transport
O2 consumption drops
[NADH] and [FADH2] increase
Inhibition of CAC, PDH
Coupling in Oxidative Phosphorylation
High energy use
Decrease in H+ gradient
Increased e- transport
O2 consumption increases
[NADH] and [FADH2] decrease
Activation of CAC, PDH
Coupling of ATP synthesis to
electron transport
2e
2e-
matrix -
H+
H2O
NADH ½ O2 + 2H+ H+
NAD+
ADP + Pi
Protons may enter matrix through a separate
ATP
process, generating heat instead of ATP
Brown Adipose Tissue
A. It will increase.
B. It will decrease.
C. It depends on if NADH or FADH2 is being
oxidized.
D. It will not change.
2,4-dintrophenol: An effective “diet
pill” that can prove to be fatal
A. ADP + Pi
B. An uncoupler of oxidative 2 3
phosphorylation
O2 consumed
ATP Synthesized
C. NADH
1
D. An inhibitor of ATP synthase
E. None of the above
Time