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