ELECTRON TRANSPORT AND

OXIDATION COMPLEXES AND

COFACTORS

PP Leong

Study Objectives

To outline the energy flow in cellular respiratory process

To outline the role of mitochondrial, ATP and energy carrier
molecules
To describe the key steps in

Electron transport chain (ETC)

Oxidative phosphorylation

To outline the roles of cofactors in ETC

To outline the functions and classical examples of
mitochondrial transport systems
To outline the pathological effects of reactive oxidative
species (ROS)
To relate classical clinical abnormalities associated with ETC
and ROS

Introduction

Energy

What is it?
Why is it so important?
How is it being generated?
How is it being stored?

Energy-Producing and Energy-Utilizing System

Overview of Cellular Respiration

Lipid
Protein
Acetyl
CoA

The Energy Currency

ATP
Hydrolysis of high energy phosphate
bonds

~7.3 kcal/mol

Usage:

Formation of new bonds

Transfer of phosphate group

Change in conformation of
molecules

Amplify signals

Transport molecules across

membrane

Lost as heat (contribute to

body temperature)

Electron Carrier Molecules

Adenine Nucleotide Coenzymes

Pyridine dinucleotides

NAD+

Flavin adenine
dinucleotide

NADP+

Two-electron carriers

Energy Transfer of Electron Carrier

NADP+
FAD

Energy Transfer of Electron Carrier

The Powerhouse

Mitochondria

http://www.cob.lu.se/dehydrogenase/

Electron Transport Chain (ETC)

Comprises a series of electron carriers

Located in the inner mitochondrial membrane
Arranges in order of increasing reduction potential
(increased affinity to electrons)

Consists of a sequence of linked oxidation-reduction

reactions
NADH + H+ NAD+ + H2O
FADH2 FAD+ + H2O

Complex

Component s

I (NADH dehydrogenase)

FMN, Fe-S centres

II (Succinate dehydrogenase)

FAD, Fe-S centers

III (Cytochrome reductase)

Cyt b, cytc, Fe-S centre

IV (Cytochrome oxidase)

Cyta, cyta3, copper (Cu1+/Cu2+)

Inter-membrane space
Inner membrane
Matrix space

NADH reductase

Cytochrome B-c1
complex

Cytochrome
oxidase complex

Key Points About ETC

1.

2.

3.

4.

Protons (H+) are translocated across the membrane, from the

matrix to the intermembrane space
Electrons are transported along the membrane, through a
series of protein carriers
Oxygen is the terminal electron acceptor, combining with
electrons and H+ ions to produce water
As NADH delivers more H+ and electrons into the ETC, the
proton gradient increases, with H+ building up outside the
inner mitochondrial membrane, and OH- inside the membrane.

Oxidative Phosphorylation

Energy released by the ETC is used to make ATP

Can be explained by 2 theories

A proton gradient is created across the inner membrane

Chemical coupling hypothesis

Chemiosmotic coupling theory
Consists of a pH gradient (pH) & gradient of charges () across the
membrane
Favorable for the protons to flow back into the mitochondrial matrix

This flow is coupled to the synthesis of ATP from ADP + Pi

catalyzed by ATP synthase

Protons (+ve) enter back into the mitochondrial matrix through

channels in ATP synthase enzyme complex. This entry is coupled to
ATP synthesis from ADP and phosphate (Pi). ADP + Pi ATP

Summary of ATP Generation

Protons are translocated across the membrane, from the

matrix to the intermembrane space, as a result of electron
transport resulting from the formation of NADH by
oxidation reactions. The continued buildup of these protons
creates a proton gradient.
ATP synthase is a large protein complex with a proton
channel that allows re-entry of protons.
ATP synthesis is driven by the resulting current of protons
flowing through the membrane:
ADP + Pi ATP

Net ATP Yield from Complete Aerobic

Oxidization of Glucose

eesc.columbia.edu/courses/ees/li...t20.html

Cofactors in ETC
Functions
NAD+ or NADP+

Electron acceptor/carrier

FAD

Electron acceptor /carrier

Coenzyme Q (CoQ) or
ubiquinone

Mobile electron carrier

Flavin mononu8cleotide
(FMN)

Mediating electron transfer between carriers

Heme

With Cytochrome C (mobile electron carrier)

Iron-sulfur Centre (present

in most electron transfer
proteins)

Electron transfer

Coenzyme

Prosthetic
group

Vitamins are precursors of cofactors

Substrate Transport System

Limited
permeability

Little/no
permeability
barrier

Located at the inner

mitochondrial membrane
Facilitate selective movement of
various substrates and
intermediate back and forth
across the inner mitochondrial
membrane
Can operate against a
concentration gradient
Energy-consuming reaction

Various Transport Systems in Mitochondria

Clinical Correlation:

Cyanide Poisoning

Inhalation or ingestion of
cyanide compounds
Source of cyanide in fire
smoke
Wool, silk, cotton, paper
Plastic & other polymer

Source of cyanide in food

Lima beans, apples,

peaches, apricots, barley,
sorghum, flaxseed, and
bamboo shoots

Biochemical consequences
Blocks aerobic metabolism & energy production
cellular hypoxia
Inhibition at the cytochrome oxidase - bind to heme
group (Fe3+) prevent utilization of O2
Cause shift to anaerobic metabolism
accumulation of lactate
Death from central respiratory arrest
Treatment
Determining factors: time (rapid) & concentration of
exposure (high or prolonged)
Antidote (nitrates, thiosulfate) to convert cyanide to
thiocyanate excreted through renal

Classical Signs & Symptoms

Normal to pink skin colour

Bright red retinal veins and
arteries
Smell of bitter almonds on the
skin and breath
Presence of soot in mouth or
nose in smoke-inhalation
victims
Cease respiration tissue anoxia - rapid cell
death (esp. the heart and CNS)

By- Products of Oxidative Processes

Reactive Oxygen Species (ROS)

An atom or molecule contain independently with one or more

unpaired electron in its outer electron shell

Superoxide anions (O2-), Hydroxyl radical (OH), hydrogen peroxide

(H2O2)

Unstable and highly reactive and swift to combined with other

atoms to stabilize its electron imbalance

Damage to all major macromolecules (e.g. lipid membrane)

Promote mitochondrial and nuclear DNA damages mutations
Leakage from mitochondria
respiration

Endogenous mechanism to
neutralized ROS
Isozyme of superoxide dismutase
Glutathione peroxidase
Glutathione reductase

Antioxidant compounds
Vitamin C and E
Food & beverages e.g. green tea,
fruits

Clinical Correlation:

Myocardial Reperfusion Injury

Heart
Attack

Infarction
Ischemia

To restore blood
flow to oxygenReperfusion deprived tissue as
quickly as possible

Proposed mechanisms of the injuries

Formation of ROS
Neutrophil-mediated myocardial and
endothelial injury
Myocyte hypercontracture (irreversible
cell shortening)
Induction of apoptosis

Injuries

Altered permeability and

electrolyte balance calcium
overload abnormal cardiac
action potential
Promote secretion of histamine
(mast cell) inflammation &
vasoactive effects

Reversible injury

Progression
of necrosis - stunning

Reducing/preventing
infarct expansion

Schematic illustration of the progression of myocardial

ischemic injury and its modification by restoration of flow (reperfusion).
FROM ROBBINS

FROM ROBBINS

Summary

Cellular respiration
ETC & oxidative phosphorylation
Roles of cofactors
By-products ROS
Clinical examples
Cyanide poisoning
Myocardial Reperfusion Injury

THANK YOU