Lecture 20: Oxidative Phosphorylation Part I Flashcards
1
Q
Size and Shape of Mitochondria
A
- Oval shaped organelles
- Comparable to the size of bacterium
- Dimensions: 2 µm long and 0.5 µm wide
2
Q
Ultrastructure of Mitochondria?
A
- Have two membrane systems
– Outer membrane (permeable due to presence of porin aka VDAC)
– Inner membrane (impermeable, has metabolite transporters, folded into series of cristae) - Have two compartments:
– Intermembrane space
– Matrix (site of TCA cycle and fatty acid oxidation) - Oxidative phosphorylation (Ox Phos) occurs in inner membrane
3
Q
Describe the mitochondrial genome
A
- Mitochondria: semi autonomous organelles
- Endosymbiotic relationship with host cell
- Free living organism engulfed by another cell
- Genome ranges in size between species
- Have their own DNA, make proteins and RNAs
- Sequence data shows all mitochondria derived from Rickettsia prowazekii due to a single endosymbiotic event
- Human mitochondrial DNA has 16,569 bp and encodes 13 respiratory chain proteins, rRNAs, tRNAs
4
Q
Give an overview of oxidative phosphorylation
A
- TCA cycle generates NADH and FADH2
- In Ox Phos these high energy electrons flow through 4 protein complexes called the electron transfer chain (ETC)
- Electrons reduce molecular O2 to water
- Three of the complexes pump protons from matrix to intermembrane space
- Protons return to matrix by flowing through another complex called ATP synthase
- This process powers the synthesis of ATP
- See Slide 10
5
Q
Describe the components of the electron transport chain
A
- Electrons transferred from NADH to O2 via three large protein complexes
– NADH Q oxidoreductase
– Q cytochrome c oxidoreductase
– Cytochrome c oxidase - Electron flow exergonic
- Powers flow of protons across inner membrane
- Fourth complex is Succinate Q reductase
- Has succinate dehydrogenase which generates FADH2 in TCA cycle
- Electrons from FADH2 enter through Q cytochrome c oxidoreductase
- Succinate Q reductase does not pump protons
6
Q
What are the first four complexes (and names) of the electron transport chain
A
- NADH Q oxido reductase: Complex I
- Succinate Q reductase: Complex II
- Q cytochrome c oxidoreductase: Complex III
- Cytochrome c oxidase: Complex IV
- See Slide 13, and note the respirasome
7
Q
List and describe the two electron carriers
A
- Coenzyme Q aka ubiquinone
- Transfers electrons from NADH Q oxidoreductase and the Succinate Q reductase to Q cytochrome c oxidoreductase
- Coenzyme Q has long tail made of 5 – C isoprene units which makes it hydrophobic
- Most common is CoQ 10
- Cytochrome c
- Shuttles electrons from Q Cytochrome c oxidoreductase to cytochrome c oxidase
- Final component of the ETC
- Catalyzes reduction of O2
Review Slide 15-17…carefully
8
Q
Describe Iron Sulfur Clusters
A
- Iron sulfur clusters present in iron sulfur proteins aka nonheme iron proteins
- Play role in reduction reactions
- Exist in various configurations:
– 1 iron ion tetrahedrally coordinated to 4 SH grps of 4 Cys residues of the protein
– 2 iron ions, 2 inorganic sulfides and 4 Cys residues (2Fe-2S)
– 4 iron ions, 2 inorganic sulfides and 4 Cys residues (4Fe-4S) - Undergo oxidation –reduction reactions but the protons never leave the protein
- Example: NADH-Q-oxidoreductase. Contains both 2Fe-2S and 4Fe-4S clusters.
9
Q
Describe Freidrich’s Ataxia
A
- Friedreich’s Ataxia is a rare inherited disease
- The disorder is recessive
- Caused by mutations in the protein Frataxin
- Small mitochondrial protein crucial for the synthesis of Fe-S clusters
- Mutations lead to loss of function
- Affects CNS, PNS, heart and skeletal system
- Nervous system damage (degeneration and thinning of spinal cord and peripheral nerves and the cerebellum)
- Damage result in impaired muscle coordination (ataxia) involving awkward, unsteady movements and impaired sensory functions
- Symptoms begin in childhood and worsen over time.
- Most common mutation is trinucleotide expansion in Frataxin gene
10
Q
Describe Complex I
A
- Complex I aka NADH dehydrogenase aka NADH-Q oxidoreductase
- Large protein (>900 kDa, with 46 polypeptide chains)
- Encoded by both nuclear and mitochondrial genes
- L shaped with a horizontal arm lying in the inner membrane and vertical arm that projects into matrix
- First point of entry of electrons from NADH
Reaction Catalyzed By Complex I:
NADH + Q + 5H+inthematrix —> NAD+ + QH2 + 4H+inthecytoplasm
- See Slides 23-24
11
Q
Describe Complex II
A
- FADH2 enters the ETC through Succinate-Q reductase complex (Complex II)
- FADH2 does not leave the complex
- Its electrons transferred to FeS and then to Q to form QH2
- Does not pump protons
- Consequently less ATP synthesized from oxidation of FADH2
12
Q
What reaction occurs in Complex III
A
- Electrons from QH2 are passed on to cytochrome c by cytochrome c oxidoreductase aka Complex III
- Flow of electrons through this complex leads to transport of 2 protons to cytoplasmic side
- See Formula on Slide 26
- See Slide 27-28
13
Q
Describe Cytochrome C oxidase
A
- Last complex aka Complex IV
- Cyt c oxidase catalyzes transfer of electrons from reduced Cyt c to molecular oxygen, the final acceptor
- Makes these reactions aerobic
- Makes humans “breathe”
- Four electrons funneled to oxygen to reduce it to water
- Concomitantly protons are pumped from matrix to cytoplasmic side of inner membrane
- See Slides 30-33
14
Q
Describe Free Radicals
A
- Complete reduction of oxygen forms water
- Partial reduction forms dangerous species
- Transfer of a single electron to oxygen forms superoxide anion
- Transfer of 2 electrons to oxygen forms hydrogen peroxide
- Hydroxyl radical formed from both
Pathological Conditions that may entail free radical injury:
- Parkinson’s Disease
- Ischemia: Reperfusion Injury
- See Slide 35-36
15
Q
Give the formulas for the two antioxidants:
superoxide dismutase,
And Catalase
A
Might be easier to see slide 37. Formulas are hard.
Then see slides 38-40
