Download Oxidative phosphorylation RESP312







ATP as energy currency
Mitochondria and the electron transport chain organization
Inhibitors of the electron transport chain
Oxidative phosphorylation and the uncoupling proteins
Inherited defects in oxidative phosphorylation.
The role of mitochondria in apoptosis
Δ Gº -7.3 kcal/mol/bond
Electron transport chain (ETC) is a system of electron transport that
uses respiratory O2 to finally produce ATP (energy)
ETC is located in the inner mitochondrial membrane
& is the final common pathway of metabolism

Energy-rich molecules as glucose or fatty acids are metabolized by a series of
metabolic reactions yielding CO2 and H2O .

The metabolic intermediates of these reactions give electrons to specialized
co-enzymes NAD and FAD to form NADH and FADH2 which donate a pair of
electrons to specialized set of electrons carriers, named the electron
transport chain, ECT (Respiratory chain).

As electrons are passed down the electron transport chain, they lose much of
their energy. Part of this energy can be taken and stored by production of ATP
from ADP and inorganic phosphate Pi (Oxidative phosphorylation).
The remainder of the free energy not trapped as ATP is released as heat
Energy-rich molecules as glucose, fatty acids & amino acids
are metabolized by a series of metabolic reactions yielding CO2 and H2O
Energy is produced as ATP or heat
Energy-rich
reduced
Coenzymes
NADH & FADH2
PHOSPHORYLATION
OXIDATION
Diet Carbohydrates
Glycogen (liver & Sk. Ms.)
Glucose
GLYCOLYSIS (in cytoplasm)
CATABOLISM OF
CARBOHYDRATES
Pyruvate
in mitochondria
Acetyl CoA
Citric Acid Cycle
(in mitochondria)
NADH & FADH2
Electron transport chain (flow of electrons)
Formation of ATP
(oxidative phosphorylation)
Energy released from NADH & FADH2 entering ETC
The transport of a pair of electrons from NADH (and FMNH2)
to oxygen
via the electron transport chain produces energy which is
more than sufficient to produce 3 ATPs from 3 ADP and 3 Pi.
The transport of a pair of electrons from FADH2 to oxygen via
the ETC
produces sufficient energy to produce 2 ATPs from 2ADPs.
OXIDATIVE PHOSPHORYLATION OCCURS IN THE MITOCHONDRIA
OXIDATIVE PHOSPHORYLATION OCCURS IN THE MITOCHONDRIA
OXIDATIVE PHOSPHORYLATION OCCURS IN THE MITOCHONDRIA
Electron transport chain
Electron transport chain is formed from five separate enzyme complexes called complexes I, II, III, IV and V
Complexes I, II, III and IV contain parts of the electron transport chain, while complex V catalyzes ATP
synthesis (phosphrylation).
Each carrier of the electron transport chain can receive electrons from a donor and can subsequently
donate electrons to the next carrier in the chain.
The electrons finally combine with O2 and proton (H+) to form H2O.
This requirement for O2 makes the electron transport process the respiratory chain .
Inhibitors of Electron transport chain
Inhibitors of ETC are compounds that prevent the passage of electrons by
binding to a component of the chain and subsequently blocking the
oxidation/reduction reactions.
As ETC and oxidative phosphorylation are tightly coupled, inhibition of the
ECT also inhibits ATP synthesis. E.g: cyanide and CO poisoning
How the free energy generated by the transport of electrons
by ECT is used to produce energy (ATP)
Coupling of ECT to phosphorylation of ADP to ATP
Transfer of electrons across
electron transport chain
FREE ENERGY RELEASED
Transport of protons (H+)
across the inner mitochondrial
membrane from the matrix to
the intermembrane space.
This creates an electrical
gradient with more +ve charge
on the outside of the membrane
than on the inside and a pH
gradient with lower pH on
outside.
Protons reenter (goes back) the
mitochondrial matrix by passing
through a channel in the complex V
(ATP synthase complex) giving
an energy that is required for the
synthesis of ATP from ADP and Pi.
(phosphorylation)
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 creates an electrical gradient with more +ve charge on the outside of
the membrane than on the inside and a pH gradient with lower pH on
outside.
Protons reenter (goes back) the mitochondrial matrix by passing through
a channel in the complex V (ATP synthase complex) giving an energy that
are required for the phosphorylation of ADP to ATP.
Oligomycin binds to ATP synthase closing the H+ channel preventing reentry
of protons to the matrix & thus preventing phosphorylation of ADP to ATP
Accordingly, electron transport chain (ETC) is stopped (as ETC &
phosphorylation are coupled)
ATP
PHOSPHORYLATION
OXIDATION
NADH
Oxidative Phosphorylation (in mitochondria):
Oxidation: electron flow in electron transport chain (with production of energy)
Phosphorylation: phosphorylation of ADP to ATP
Uncoupling proteins (UCP)
Uncoupling proteins (UCPs) are located in the inner mitochondrial
membrane leading to proton leak as they allow protons to reenter the
mitochondrial matrix with no accompanying synthesis of ATP (no
phosphorylation of ADP to ATP).
No energy is utilized for the process of ATP synthesis, although ETC is
functioning….i.e. The process of ETC is not coupled to posphorylation.
However, energy is released in the form of heat.
UCP1 (also called thermogenin) is responsible for the
activation of fatty acid oxidation and heat production in the
brown fat of mammals.
Brown fat uses 90% of energy of ETC for thermogenesis in
response to cold at birth & during arousal in hibernating
Animals (by help of UCPl1).
Humans have little of the brown fat (except in the newborn
Uncoupling proteins (UCP)
Synthetic uncouplers are compounds that can uncouple ETC &
phosphorylation by increasing the permeability of the inner
mitochondrial membrane to protons (thus will not reenter through ATP
synthase)
Examples:
* 2,4-dintrophenol
An uncoupler that causes electron transport to proceed at a
rapid rate without phosphorylation & thus energy is released
as heat rather than being used to synthesize ATP
* High dose of aspirin (salicylates)
uncouples oxidative phosphorylation causing fever (observed with toxic
overdose of aspirin)

Mitochondrial DNA (mtDNA) is maternally inherited as mitochondria of sperm
cell do not enter the fertilized ova.

Mitochondrial DNA (mtDNA) codes only for 13 polypeptide (of total 120)
required for oxidative phosphorylation.
(while the remaining are synthesized in the cytosol & are transported into the
mitochondria).

Defects of oxidative phosphorylation usually results from alteration in mtDNA
(mutation rate 10 times more than that of nuclear DNA).

Tissues with greater ATP requirement (as CNS, sk.ms. & heart muscles, kidney
& liver) are most affected by defects in oxidative phosphorylation.

Examples for diseases caused by mutations in mtDNA:
1- Mitochondrial myopathies
2- Leber hereditary optic neuropathy
Mitochondria and apoptosis
initiated by the formation of pores in the outer
Mitochondrial membrane
pores allow cytochrome c to leave and enter
the cytosol
+ proapoptotic factors, activates a family of
proteolytic enzymes ,the caspases
cleavage of key
proteins and
resulting in the
morphologic
and biochemical
changes
characteristic
of apoptotic
cell death