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Oxidative phosphorylation
NADH transportOxidative phosphorylation
p691
Only those with specific transporters can pass
All pathways related to fuel oxidation except glycolysis
N side
Oxidative phosphorylation
• Converting the energy from electrons (from NADH and FADH2) to ATP
1. NAD+
2. FAD3. Ubiquinone4. Cytochromes5. Iron-sulfur proteins
Five electron carrying molecules
Ubiquinone (coenzyme Q; Q; Q10)
UbiquinonePlastoquinone (plant chloroplast)Menaquinone (bacteria)
p693
p694cytochromes
p695
Iron-sulfur proteins
Method for determining the sequence of electron carriers
p696
A B C D E F
A B C D E F
A B C D E F
p698
Chemical uncouplers• 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.
p707
Ionophores
• Valinomycin (an ionophore) allows inorganic ions to pass easily through membranes. This will uncouple electron transfer from oxidative phosphorylation.
p406
p696
p698Complex I
p697
Complex I & II
p700Complex III
p702Complex IV
H+H+H+H+H+H+H+H+H+H+H+H+
III
Cyt cCyt c
H+H+H+H+
III
IV
NADH
NAD+
e
e
Qee
H+H+OH2OH2O
NADH
FADH2
eFAD
e
H+H+O
FADH2
Mitochondrial inner membrane
Mitochondrial matrix
Mitochondrial intermembrane
space
p703
p675
p711Mitochondrial ATP synthase complex
p687Oxidative phosphorylation in brown fat tissue is uncoupled with ATP synthesis
p718Regulation
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.
Aspartate
p715Malate-aspartate shuttle
NADH
NAD+
OAA
malateMalate
dehydrogenase
NAD+
NADHOAA
Glutamate
-KG
Malate dehydrogenase
Aspartate aminotransferase
Aspartate aminotransferase
NAD+Glycerol 3-phosphate
p715Glycerol 3-phosphate shuttleNADH
DHAP
DHAP
FAD
FADH2
Q
Cytosolic glycerol 3-phosphate
dehydrogenase
Glycolysis
III
NADHGlc G6P F6P F1,6BP G3P
DHAP
1,3BPG 3-PGA 2-PGA PEP Pyruvate
NADH
NADHFADH2
NADH
Malate-aspartate
shuttle
Glycerol 3-phosphate
shuttle
p720Mitochondrial genome
p35
Mitochondrion is probably evolved from endosymbiotic bacteria
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 ragged-red 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 adult-onset (type II) diabetes.
Many respriatory proteins are encoded by mitochondria
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