Download Iron-sulfur proteins

p691
Only those with specific
transporters can pass
N side
All pathways related to
fuel oxidation except
glycolysis
Oxidative phosphorylation
• Converting the energy from electrons (from
NADH and FADH2) to ATP
• Electron transfer occurs in oxidative
phosphorylation:
1. Direct transfer to reduce cation, Fe3+
Fe2+
2. Transfer as hydrogen atom
3. Transfer as hydride ion (:H-)
Five electron carrying molecules
1. NAD+
2. FAD
3. Ubiquinone
4. Cytochromes
5. Iron-sulfur proteins
Ubiquinone (coenzyme Q; Q)
Ubiquinone
Plastoquinone (plant chloroplast)
Menaquinone (bacteria)
p693
cytochromes
p694
Iron-sulfur proteins
Iron-sulfur proteins
p695
Method for determining the
sequence of electron carriers
p696
p696
p705
Oxidative phosphorylation
Complex I
NADH +H+
NAD+
FMN
Fe2+S
CoQ
FMNH2
Fe3+S
CoQH2
p698
NADH +H++Q --> NAD++QH2
4 protons pump out
Complex I & II
Succinate
FAD
Fe2+S
CoQ
Fumarate
FADH2
Fe3+S
CoQH
p697
Complex III
p700
CoQH2
cyt b ox
Fe2+S
cyt c1 ox
cytcred
CoQ
cytbred
Fe3+S
cytc1red
cytcox
QH2+2Cytc1oxidized+2HN+ --> Q+2Cytc1reduced+4Hp+
Complex IV
cyt c red
cyt a ox
cyt a3 red
O2
cyt c ox
cyt a red
cyt a3 ox
2 H2O
p702
4Cytcreduced+8HN++O2 --> 4Cytcoxidized+ 4Hp++2H2O
p703
p703
p706
QH2 oxidase
(resistant to cyanide)
p675
p698
Chemical uncouplers
p707
• Chemicals like DNP
and FCCP are weak
acid with hydrophobic
properties that permit
them to diffuse readily
across mitochondrial
membranes. After
entering the matrix in
the protonated form,
they can release a
proton, thus disspating
the proton gradient.
p406
Ionophores
• Valinomycin (an
ionophore) allows
inorganic ions to pass
easily through
membranes. This will
uncouple electron
transfer from oxidative
phosphorylation.
Mitochondrial ATP synthase complex
p711
NADH transport
• NADH produced by glycolysis must be
transported into mitochondria to produce
ATP.
• However, NADH cannot enter mitochondria
directly. Instead it is transported by the form
of malate or glycerol 3-phosphate.
Malate-aspartate shuttle
p715
Glycerol 3-phosphate shuttle
p715
Oxidative phosphorylation in
brown fat tissue is uncoupled
with ATP synthesis
p687
Regulation
p718
Mitochondrial genome
p720
Mitochondrial
encephalomyopathies
• Mutations in mitochondrial genes cause
mitochondrial encephalomyopathies that
affecting primarily the brain and skeletal
muscle. Because infants inherit their
mitochondria from their mothers, so
mitochondrial encephalomyopathies are
maternal-linked.
Leber’s hereditary optic
neuropathy (LHON)
• LHON is the result of
defective
mitochondrial genes
that are involved in
electron transfer.
• Vision loss usually
occurs between the
ages of 15 and 35.
Myoclonic epilepsy and raggedred fiber disease (MERRF)
• Mutation in the
mitochondrial gene
that encodes a tRNA
specific for lysine
(lysyl-tRNA) results in
MERRF.
• Synthesis of several
proteins require this
tRNA is interrupted.
p720
MERRF
• MERRF patients often
have abnormally
shaped mitochondria
containing
paracrystalline
structures.
• This lysyl-tRNA
mutation is also one of
the causes of adultonset (type II)
diabetes.
Many respriatory proteins are
encoded by mitochondria
Mitochondrion is probably evolved from
endosymbiotic bacteria
p35
Bacteria do have respiratory
chain enzymes
• For example, E. coli
has NAD-linked
electron transfer from
substrate to O2,
coupled to the
phosphorylation of
cytosolic ADP.
Mitochondria, apoptosis, and
oxidative stress
Mitochondria is not only involved in
ATP synthesis. It is also involved in
cellular damage and death.
The role of mitochondria in
apoptosis
• When cell receives a signal for apoptosis,
one consequence is the permeability of the
outer mitochondrial membrane will
increase, allowing cytochrome c release.
• The release of cytochrome c will activate
caspase 9, which will initiate the protein
degradation process.
Mitochondria can produce
superoxide free radical
Mitochondria and oxidative stress
• Antimycin A inhibits
complex III by
occupying the QN site,
which may increase
the likelihood of
superoxide radical
formation and cellular
damage.
The role of mitochondria in
oxidative stress
PPP