bioenergetics module 3. sabah
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Prof. Dr. Sabah Abdel-Hady
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Bioenergetics describes the energy changes
during biochemical processes.
Energy is the capacity to perform work
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a) Heat energy that maintains the bodytemperature at 37oC
b) Free energy that performs work e.g.mechanical work muscle contraction
electrical work nerve impulses transmission
chemical work synthetic reactions
osmotic work active secretion & active
absorption
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*** High-Energy compounds liberate on hydrolysismore than 7 Kcal/mole.
High energy phosphate bonds:
Contain high-energy and is written as e.g. 1,3-
biphosphoglycerate , phosphoenol pyruvate,
creatine phosphate, nucleotides as ATP
High energy sulphate bonds:
1- S-adenosyl methionine (SAM).
2- Phosphoadenosine phosphosulfate (PAPS).
*** Low-energy compounds produce, onhydrolysis, 2-4 (below 7) Kcal. of free energy permole, e.g. phosphate ester bond in sugar
phosphates G-6P.
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Storage of energy
1) ATP; the common currency of energy
2) Creatine phosphate
ATP+ Creatine
creatine kinase
ADP+ creatine phosphate.
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Cells harvest energy by breaking bonds
and shifting electrons from one molecule
to another.
aerobic respiration - final electron acceptor isoxygen
anaerobic respiration - final electron acceptor
isinorganic molecule other than oxygen
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Mechanism of energy collection.
1)Substrate level
2)Oxidative phosphorylation at the
respiratory chain
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1)Substrate level phosphorylation inwhich high-energy phosphate is transferred
from the substrate to ADP to form ATP. e.g.
conversion of 1,3 biphosphoglycerate to 3-
phosphoglycerate by phosphoglycerate kinase
with the formation of ATP.
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Mitochondrial Electron Transport
Chain
System of Linked
Electron Carriers
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Components of Electron
Transport Process
Reoxidation of NADH and FADH2
Sequential oxidation-reduction ofmultiple redox centers (four enzymecomplexes)
Production of proton gradient acrossthe mitochondrial membrane
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Oxidative Phosphorylation
Synthesis of ATP driven by free
energy of electrochemicalgradient
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Overall Reaction
(Oxidation of NADH by O2)
N A D H + H + + 1/2 O2
N A D + + H2O
E o ' = + 0.815 V ( 0.315 V ) = 1.130 V
G o ' = nFE o '
G o ' = 218 kJ /m o l
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ATP Synthesis
A DP + P i ATP
G o ' = + 30.5 k J/m ol
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It is final common pathway in aerobiccellsby which electrons derived from varioussubstances are transferred to O2 to form H2O.
ETC is formed of a series of electron carriers,which catalyze the transfer of electrons fromreduced coenzymes to oxygen.
The energy released is utilized for
synthesis of high energy phosphate bonds(conversion of ADP + Pi ATP).
Heat production
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Hydrogen and electrons flow through the
respiratory chain from the more electronegative
components ( NADH) to the more electropositive
O2i.e. in the order of increase in redox potential.
The redox span from NAD+/NADH to O2/H2O is 1.1volts
Electrons move from a carrier with low
reduction potential (high tendency to donateelectrons) toward carriers with higherreduction potential (high tendency to acceptelectrons).
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The respiratory chain exists in the inner
mitochondrial membrane and consists of a series of
catalysts (= redox carriers) that collect and transportreducing equivalents (hydrogen or electrons) from
NAD-linked dehydrogenase system, through
flavoproteins and cytochromes, and finally to
molecular oxygen to form water.
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Kinetics and Mechanismsof
Transport
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The components of the respiratory chain
Located in the inner mitochondrial membrane.
Formed of a series of 4 complexes ,
coenzyme Q and cytochrome C .
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Mitochondrial Electron Transport
Chain
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NAD+
FMN
FeS
ubiquinoneFAD FeS
Cyt b
FeS Cyt c1 Cyt c Cyt a Cyt a3
1/2 O2
ubiquinone
NAD+ or FAD
There are 2 sites of entry
for electrons into the
electron transport chain:
Both are coenzymes for
dehydrogenase enzymes
The transfer of electrons is not directly to oxygen but
through coenzymes
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Electron Transport chain(respiratory chain)
The electron transport chain in the innermitochondrial membrane can be isolated infour proteins complexes(I, II, III, IV).
A lipid soluble coenzyme (Q) and a watersoluble protein (cyt c) shuttle betweenprotein complexes
Electrons transfer through the chain - fromcomplexes I and II to complex IV
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Complex I: is (NADH:ubiquinone oxidoreductase,or NADH dehydrogenase.)
It is formed of :
Many polypeptides
FMN coenzyme
Seven iron sulfur centers(fes) which are
necessary for the transfer of hydrogen atoms tothe next member of the chain (coenzyme Q).
It catalyzes the transfer of electrons from NADH
+H+ to coenzyme Q(ubiquinon).
Electrons or hydrogens are transferred fromNADH to FMN then to different fes centers and
finally to UQ to form reduced UQ H2 (ubiqinol) .
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H3C
H3CN
N
N O
O
N
CH2 CH CH CH CH2
OH OH OH
O P OH
OH
O
riboflavin monophosphate(flavin mononucleotide, FMN)
H3C
H3C NN
N O
O
N
CH2 CH CH CH CH2
OH OH OH
O P O P O
OH
O
OH
O
CH2 O
OH OH
N
N
NH2
N
N
flavin adenine dinucleotide (FAD)
FAD Always a 2-electron reaction transferring 2 e- and 2 H+
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Fe
Fe
SS
S
FeFe
S
S
S
S
S
Cys
Cys
Cys
Cys
S
Fe
S
Fe
S
S
S
S
Cys
CysCys
Cys
Iron-Sulfur CentersTwo iron-sulfur centers
from complex I
4-iron Fe-S
2-iron Fe-S
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Coenzyme Q(CoQ, Q or ubiquinone) is lipid-soluble.
It dissolvesin the hydrocarbon core of a membrane.
the only electron carrier not bound to a protein.
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Complex II: ( succinate:ubiquinoneoxidoreductase.)
Is formed of:
Succinate dehydrogenase.FAD coenzyme.
Two iron sulfur centers.
It catalyzes the transfer of electrons or
hydrogens from succinate to UQ to form
UQH2.
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COO
C
C
COO
H H
H H
COO
C
C
COO
H
H
Q QH2
via FAD
succinate fumarate
Succinate Dehydrogenase
Com lex II
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The heme iron can undergo 1 e- transitionbetween ferric and ferrous states: Fe3+ + e-
Fe2+
Copper ions besides two heme A groups (aand a3) act as electron carriers in Cyta,a3
Cu2++e- Cu+
Heme is a prosthetic group ofcytochromes.
Heme contains an iron atom in a porphyrin ring
system.
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N
N
N
N
CH3 HC
CH3
S CH2
CH3
CH S CH2
CH3
CH2
CH2
COO
CH3
H3C
CH2CH2
OOC
protein
protein
Fe
Heme c
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NAD+, flavins and Q carry electrons and H+
Cytochromes and non-haem iron proteins carry only
electrons
NAD+ FAD undergoes only a 2 e- reaction;
cytochromes undergo only 1e- reactions
FMN Q undergoes 1e- and 2 e- reaction
Electron carriers
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NAD+
FMN
FeS
ubiquinoneFAD FeS
Cyt b
FeS Cyt c1 Cyt c Cyt a Cyt a3
1/2 O2
ubiquinone
I
II
III IV
NADH Dehydrogenase
Succinate
dehydrogenase
CoQ-cyt c Reductase
Cytochrome Oxidase
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When a substrate is oxidized via NAD-linked
dehydrogenase, three molecules of ATP are
formed.
when a substrate is oxidized via aflavoprotein-linked dehydrogenase, only
two molecules of ATP are Formed
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Mechanism of oxidative phosphorylation (Mitchell'schemiosmotic theory)
Oxidation of components of the respiratory chainleads to generation of protonsinside themitochondrial matrix that are pumped to the outsideof the inner membrane.
ComplexesI,III and IV act as proton pumps
This resultsin accumulation of protons outside theinner membrane which in turn creates anelectrochemical potential difference across the innermembrane leading to formation of ATP from ADP andPi by the enzyme ATP synthase
ATP synthase is formed of two subunits F0 & F1 .
The F0 subunit protrude into mitochondrial matrixand acts as a gate or channel for protons
F1 subunits present in the inner mitochondrialmembrane, it catalyzes the synthesis of ATP.
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As protonscross the membrane through the channel
in the base of ATP synthase
the FO proton-driven motor rotate
This movement provides the energy
for the active sites of F1
that produces and then releases ATP
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ADP/ATP Exchanger
Electrogenic Antiporter
Driven by electrochemical gradient
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Control of Respiratory Chain
The respiratory chain iscontrolled by thelevels of ADP and Pi as well as by the
availability of ADP/ATP transporter.
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Inhibitors of the respiratory
chain.A) Inhibitors of the respiratory chain proper.
B) Inhibitors of oxidative phosphorylation.
C) Uncouplers of oxidative phosphorylation.
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A) Inhibitors ofthe respiratory chain proper.
They inhibit the respiratory chain at four sitesSite 1: between FeS and Qin complex I. It is
inhibited by barbiturates, piericidin A(antibiotic) and rotenone (insecticide and fishpoison)
Site 2: between cytochrome b and cytochromec1 in complex III. It isinhibited by antimycinand dimercaprol.
Site 3: at cytochrome oxidase in complex IV. Itisinhibited by hydrogen sulfide (H2S), carbon
monoxide (CO), and cyanide.Site 4: between succinate dehydrogenase and Q
in complex II. It isinhibited by carboxin.
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B) Inhibitors of oxidative phosphorylation.
They include Oligomycin that inhibits thetransport of ADP into and the transport of ATPout of the mitochondria. Atractyloside isanother inhibitor.
C) Uncouplers of oxidative phosphorylation.
They dissociate oxidation in the respiratory
chain from phosphorylation. Oxidation becomes unlimited since it is not
controlled by the concentration of ADP or Pi.
They include 2,4 dinitrophenol, dinitrocresol,
pentachlorophenol, thyroxine, Ca2+
and m-chlorocarbonyl cyanide phenyl hydrazone(CCCP).
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Oxidation of extramitochondrial NADH.
NADH is produced in the cytosol duringglycolysisin the reaction catalyzed by
glyceraldehydes -3- phosphate
dehydrogenase.
This NADH can not enter the respiratorychain in the mitochondria because the inner
mitochondrial membrane isimpermeable toit.
reducing equivalents are transferred fromextramitochondrial NADH to the
mitochondria by one of two shuttles
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No NADH Transporter
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Aerobic glycolysis yeilds
8 ATPs if malate shuttle is used
6 ATPs if glycerophosphate shuttle is used
and accordingly complete oxidation of 1mol of glucose yields 38 or 36 ATPs.
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