Electron transport chainchapter 6 (page 73)
BCH 340 lecture 6
All of the reactions involved in cellular respiration can be grouped into three main stages
The Metabolic Pathway of Cellular Respiration
Glycolysis – occurs in cytoplasm
The Krebs cycle – occurs in matrix of mitochondria
Electron transport – occurs across the mitochondrial membrane
Oxidative phosphorylation
• Energy-rich molecules, such as glucose, are metabolized by a series of oxidation reactions ultimately yielding CO2 and water
• The metabolic intermediates of these reactions donate electrons to specific coenzymes—nicotinamide adenine dinucleotide (NAD+) and Flavin adenine dinucleotide (FAD)—to form the energy-rich reduced coenzymes,NADHand FADH2.
Oxidative phosphorylation
• These reduced coenzymes can, in turn, each donate a pair of electrons to a specialized set of electron carriers, collectively called the electron transport chain
• As electrons are passed down the electron transport chain, they lose much of their free energy. Part of this energy can be captured and stored by the production of ATP from ADP and inorganic phosphate (Pi).
• The transfer of electrons down the electron transport chain is energetically favored because NADH is a strong electron donor and molecular oxygen is an avid electron acceptor. However, the flow of electrons from NADH to oxygen does not directly result in ATP synthesis.
H+
outer
membrane
intermembrane
space
inner
membrane
matrix
e-O2
H2O
ADP+
PiATP
Figure: Essential features of oxidative phosphorylation
Redox reactions of respiratory chain use electrons to reduce oxygen to water
Energy generated moves protons from matrix to intermembrane space
Inward movement of protons recovers this energy to promote formation of ATP in the matrix.
H+
Oxidative
process
Phosphorylation
process
ATP
Synthase
• 1. Proton pump: Electron transport is coupled to the phosphorylation of ADP by the transport of protons (H+) across the inner mitochondrial membrane from the matrix to the intermembrane space
• This process creates an electrical gradient (with more positive charges on the outside of the membrane than on the inside) and a pH gradient (the outside of the membrane is at a lower pH than the inside
• The energy generated by this proton gradient is sufficient to drive ATP synthesis.
• 2. ATP synthase: The enzyme complex ATP synthase (Complex V, synthesizes ATP using the energy of the proton gradient generated by the electron transport chain.
Only 4 of 38 ATP ultimately produced by respiration
of glucose are derived from substrate-level
phosphorylation (2 from glycolysis and 2 from TCA)
The vast majority of the ATP (90%) comes from the
energy in the electrons carried by NADH and FADH2
ATP yield
Adding Up the ATPCytosol
Mitochondrion
Glycolysis
Glucose2
Pyruvicacid
2Acetyl-
CoA
KrebsCycle
ElectronTransport
bydirectsynthesis
by directsynthesis
byATPsynthase
Maximumper
glucose:
A Road Map for Cellular Respiration
High-energyelectronscarried
by NADH
High-energyelectrons carriedmainly byNADH
The components of the electron transport chain are located in the inner membrane
Redox Reactions
• REDOX short for oxidation-reduction reactions
• Chemical reactions that transfer electrons from one substance to another are called oxidation-reduction reactions
REDOX FACTS A:H A
Reductant Oxidant + e-
B B:H
Oxidant + e- Reductant
(acceptor) (donor)
Both oxidation and reduction must occur simultaneously
The reductant of one pair donates electrons and the oxidant of the other pair accepts the electrons
Red1 (AH) + Ox2 (B) Ox1(A) + Red2(BH)
• Electrons can move through a chain of donors and acceptors
• In the electron transport chain, electrons flow down a gradient
• Electrons move from a carrier with low reduction potential (high tendency to donate electrons) toward carriers with higher reduction potential (high tendency to accept electrons)
electron flow
Eo' = 0.42V
INADH Coenzyme Q
Eo' = -0.32V Eo
' = 0.10V
Eo' = 0.19V
III Cytochrome C
Eo' = 0.29V
Eo' = 0.53V
IV ½ O2
Eo' = 0.82V
Eo' = 0.07V
Eo' = 0.03V
II
Succinate
The components of the RC are arranged in order of increasing redox potential
The Eo values are the potential differences across the four complexes ( that span the mitochondrial inner membrane)
• Potential (EO): measure of the tendency of oxidant to gain electrons to become reduced.
EO: Eo of the electron-accepting pair minus the Eo of the electron-donating pair
electron flow
Eo' = 0.42V
INADH Coenzyme Q
Eo' = -0.32V Eo
' = 0.10V
Eo' = 0.19V
III Cytochrome C
Eo' = 0.29V
Eo' = 0.53V
IV ½ O2
Eo' = 0.82V
Eo' = 0.07V
Eo' = 0.03V
II
Succinate
The overall voltage drop
from NADH E0 = -(-0.32 V)to O E0 = +0.82 V is Eº = 1.14 V
The respiratory electron transport chain
RC exists as four large, multi-subunit protein complexes
complex I is a NADH-ubiquinone reductase
complex II is succinatedehydrogenase
complex III is the ubiquinone -cytochromec reductase
complex IV is cytochrome oxidase
Figure: Complex I of the respiratory chain that links NADH and coenzyme Q.
NADH Dehydrogenase (NADH-ubiquinone
reductase) accepts 2e- from NADH and
transfers them to ubiquinone (coenzyme
Q), an electron carrier
Uses two bound cofactors to accomplish
this: FMN (Flavin mononucleotide) and 6
iron-sulfur (Fe-S) protein
FAD
FADH2
Succinate
Fumarate
SDH
Complex II: Succinate-CoQ reductase
Prosthetic groups: FAD; Fe-S
CoQ
SDH is succinate dehydrogenase an enzyme of the citric acid cycle (associated with membrane)
2 e- transferred from succinate to CoQ
1 mole FADH2 produced
Figure: Complex III of the respiratory chain linking CoQ and cytochrome C.
CoQ cyt b/cyt c1
Complex III: cytochrome reductase
Prosthetic groups: heme b; heme c1; Fe-S
cyt c
Electrons from
complex I or II
Is composed of cytochome b, cytochrome C1 and iron sulphurproteins
Accepts e- from coenzyme Q and transfers e- to cytochrome c (Cytcis the only soluble cytochrome) coupled with the transfer of protons from the matrix to the intermembrane space
Figure: Complex IV -cytochrome oxidase- reducing oxygen to water
Contains cytochromes a/a3 and 2 Cu ions involved in e-
transfers
Cytochrome oxidase passes electrons from cytochrome c
through a series of heme groups and Cu ions to O2, reducing
it to H2O (end product)
ATP-synthase (complex V), present in the inner mitochondrial membrane, actually makes ATP from ADPand Pi.
ATPase used the energy of an
existing proton gradient to
power ATP synthesis.
• This proton gradient develops
between the intermembrane
space and the matrix.
• This concentration of H+ is the proton-motive force.
The ATP synthase molecules are the only place that will allow H+ to diffuse back to the matrix
This flow of H+ is used by the enzyme to generate ATP a process calledchemiosmosis
(oxidative phosphorylation)
• Multisubunit transmembrane protein
• Molecular mass = ~450 kDa
• Functional units
• F0: water-insoluble transmembrane protein
(up to 8 different subunits)
• F1: water-soluble peripheral membrane protein
(5 subunits) ,contains the catalytic site for ATP synthesis
Properties of ATP Synthase
Flow of 3 protons through ATP synthaseleads to phosphorylation of 1 ADP
Respiratory inhibitors
These compounds prevent the passage of e- by binding a component of the ETC blocking the oxidation/reduction reaction