It all reduces down to water.

Dr. Suheir Ereqat

 Basics of Redox Chemistry
Term Definition

Oxidation Loss of hydrogen

Loss of electrons

Reduction Gain of hydrogen

Gain of electrons

Oxidant Oxidizes another chemical by taking

electrons or hydrogen

Reductant Reduces another chemical by supplying

electrons or hydrogen
NADH + H + FAD NAD+FADH2
Reductant oxidant (= Redox couple)
e-donor e-acceptorDr.(oxidation-reduction
Suheir Ereqat potential)
 An Overview
• Biological oxidations are catalyzed by intracellular
enzymes. The purpose of oxidation is to obtain energy.
• Electron Transport: Electrons carried by reduced
coenzymes (NADH or FADH2) are passed sequentially
through a chain of proteins and coenzymes (so called
electron transport chain)to O2 .
• Oxidative Phosphorylation: Coupling e- Transport
(Oxidation) and ATP synthesis (Phosphorylation) .
• It all happens in the inner mitochondrial membrane
(eukaryotic cells)

Dr. Suheir Ereqat

 Reduction Potentials
E0’=standard reduction potential.
The relative tendency to accept e-s and become
reduced. Crucial equation
Go' = -nF Eo'

Number of electrons = Eo'(acceptor) - Eo'(donor)

transferred in the redox
reaction Faraday’s constant (96485
J/volt/mole)

If  Eo' is positive, an electron transfer reaction is spontaneous (Go'

<0). Electrons move spontaneously from situation of lower
reduction potential (higher energy) to higher reduction potential
(lower energy) Dr. Suheir Ereqat
 mitochondrion

One half of the cytoplasmic volume of

8
cardiac cells consists of mitochondria
 What is Electron Transport chain
(respiratory chain)
• A chain of protein complexes embedded in the
inner mitochondrial membrane. Transports
electrons and pumps hydrogen ions into the
intermembrane space to create a gradient.

• The electron transport chain in the inner

mitochondrial membrane can be isolated in four
proteins complexes(I, II, III, IV).
• Complex v: ATP synthase

Dr. Suheir Ereqat

 Complexes I-IV: Electron
Carriers
• Nicotinamide nucleotides (NAD)
• Flavoproteins(tightly bound to FAD,FMN)
• Cytochromes;b,c1, a,a3 ( heme containing
proteins)
• Iron sulfur proteins
• Copper (complex IV)
A lipid soluble coenzyme (Q) and a water soluble protein
(cyt c) shuttle between protein complexes
.
.12 Dr. Suheir Ereqat
 The heme iron can undergo a 1 e- transition between
ferric and ferrous states: Fe+++ + e-  Fe++

16
Dr. Suheir Ereqat
 4-Complexes
NAD+

FMN I. NADH-UQ oxidoreductase

I NADH Dehydrogenase
FeS

FAD FeS ubiquinone

II
Succinate ubiquinone Cyt b
oxidoreductase-Succinate
dehydrogenase Cytochrome C Oxidase
ubiquinone

FeS Cyt c1 Cyt c Cyt a Cyt a3

III IV
1/2 O2
Cytochrome bc1 complex
Dr. Suheir Ereqat
 Electron Transport Chain
Four Complexes
Complex I : catalyze electron transfer from
NADH to ubiquinone
Complex II catalyze electron transfer from
succinate to ubiquinone
Complex III carries electrons from reduced
ubiquinone (QH2) to cytochrome c.
Complex IV completes the sequence by
transferring electrons from cytochrome c to
oxygen.
– Electrons ultimately reduce oxygen to water
• 2 H+ + 2 e- + ½ O2 -- H2O

Dr. Suheir Ereqat

26 Dr. Suheir Ereqat
Complex I: NADH to Q

29 Dr. Suheir Ereqat

30 Dr. Suheir Ereqat
 Complex II: succinate to Q
• Succinate dehydrogenase
Succinate -- FAD--Fe-S---Q  fumarate
+ QH2
FAD is the initial e- acceptor FAD is reduced to FADH2 during oxidation of
succinate to fumarate.
FADH2 is then reoxidized by transfer of electrons through a series of 3
iron-sulfur centers to CoQ, yielding QH2.
The QH2 product may be reoxidized via complex III, providing a pathway
for transfer of electrons from succinate into the respiratory chain.

31 NO proton pumping!
 Other mitochondrial flavoprotein Dehydrogenase

Electron-Transferring
Flavoprotein

Reduction of Q by:
NADH DH (complexI)
Succinate DH (complex II)
G-3-p-DH
Fatty acyl coA DH
33 Dr. Suheir Ereqat
Complex III: QH2 to cytochrome c
4H

Dr. Suheir Ereqat

 Complex IV: Cytochrome C to O2

39 Dr. Suheir Ereqat

For each pair of electrons transferred to O2, 10 protons are pumped out

42 Dr. Suheir Ereqat

 Electochemical gradient = Proton-motive force

The inner mitochondrial membrane

separates two compartments of
different [H], resulting in differences
in chemical concentration and
charge distribution across the
membrane. The net effect is the
proton-motive force,

44 Dr. Suheir Ereqat

 Chemiosmosis

47
ATP synthase
stator

F1

shaft

F0

48
ATP synthesis occurs on ß- subunit of F1. Fo contains a proton channel
 Transport of Adenine nucleotide and phosphate

50

Dr. Suheir Ereqat

 E- transport coupled with phosphorylation
blocks electrontransfer
between cytochrome
oxidase (Complex IV)
and O2, inhibits both
respiration and ATP
synthesis

54
Dr. Suheir Ereqat
 Potent inhibitors of ATP synthase
After entering the matrix in the protonated form,
it can release a proton, thus dissipating the
proton gradient..

55
56 Dr. Suheir Ereqat
 Cytosolic NADH

NADH that are produced by glycolysis Pass electrons to shuttles:

• Glycerol-phosphate shuttle:
Transfers electrons from cytosolic NADH to FAD to produce FADH2

• Malate-Aspartate shuttle:
Transfers electrons from cytosolic NADH to NAD+ to produce NADH

Dr. Suheir Ereqat

Glycerol phosphate- shuttle Muscles and brain

59 Dr. Suheir Ereqat

 Liver , kidney, heart

AST AST E-transport

chain

Dr. Suheir Ereqat

62 Dr. Suheir Ereqat
 Oxidative Phosphorylation ls Regulated by
Cellular Energy Needs

The rate of respiration (O2 consumption) in mitochondria is tightly regulated;

it is generally limited by the availability of ADP as a substrate for
phosphorylation.

Dependence of the rate of O2 consumption on the availability of the Pi can

be remarkable.

Another, related measure is the mass-action ratio of the ATP-ADP system,

ATPl/([ADP].[P]).

Dr. Suheir Ereqat

65
Regulation of ATP producing pathway-
Summary