Cell Integrity Flashcards
How much energy does the average adult require?
8,400 kJ/day (83kg ATP)
What is the lifespan of an ATP molecule?
1-5 mins
How much ATP does a human contain?
250g
How many times is each ATP molecule recycled a day?
300
What does any interruption to oxidative phosphorylation lead to?
Cellular ATP depletion —> cell death
What are the 2 most common causes of OxPhos failure?
Hypoxia (less O2)
Anoxia (no O2)
How long does it take for cell death to occur after OxPhos failure in neurones vs muscle?
- Neurones —> mins
- Muscles —> hours
What is substrate level phosphorylation?
Production of ATP by the direct transfer of Pi from a substrate to ADP
What reaction occurs in the re-oxidation of NADH?
NADH + H+ + 1/2 O2 —> NAD+ + 1/2 H2O
What is the ΔG of NADH re-oxidation?
-220 kJ/mol
What reaction occurs in the re-oxidation of FADH2?
FADH2 + 1/2 O2 —> FAD + H2O
What is the ΔG of FADH2 re-oxidation?
-167 kJ/mol
What is the energy released from NADH/FADH2 re-oxidation used for?
Make phosphoanhydride bonds (between phophate groups in ATP)
What are the 5 parts of mitochondria?
- Outer membrane
- Inner membrane
- Intermembrane space
- Cristae
- Matrix
Where does OxPhos occur?
Inner mitochondrial membrane
What are cristae?
Folds of inner mitochondrial membrane to inc SA
What are the 4 membrane proteins in the ETC?
- Complex I = NADH dehydrogenase
- Complex II = Succinate dehydrogenase
- Complex III = Q-cytochrome C oxidoreductase
- Complex IV = Cytochrome C oxidase
What are the 2 mobile carriers in the ETC?
- Co-enzyme Q (ubiquinone) —> between II and III
- Cytochrome C —> between III and IV
Which protein does NADH donate its e-s to?
Complex I (NADH dehydrogenase)
Which protein does FADH2 donate its e-s to?
Complex II (Succinate dehydrogenase)
What happens as e-s pass from each membrane protein to the next?
Release energy —> actively transports H+ from matrix to intermembrane space
Where does O2 fit into the ETC?
Last step
- Complex IV (Cytochrome C oxidase) passes on e-s to O2
Why does FADH2 re-oxidation produce less ATP than NADH re-oxidation?
Bypasses complex I (NADH dehydrogenase) —> less H+ pumped —> less ATP produced
When is FADH2 produced? (3)
- TCA cycle
- B-oxidation
- Glycerol-phosphate shuttle (brain and skeletal muscle)
What are the 4 redox couples in the ETC?
- NAD+/NADH
- FAD+/FADH2
- Fe3+/Fe2+
- 1/2 O2/H20
Where is iron present in the ETC?
All proteins and carriers except Q
What is redox potential?
Ability of a redox couple to accept/donate e-s
What is E0?
Redox potential
What does the sign of the E0 indicate?
- +ve —> accepts e-s (more oxidising than H)
- -ve —> donates e-s (more reducing than H)
Why do e-s lose energy as they pass through the ETC?
Reactions are energetically favourable
What are the 6 steps of e-s transport in the OxPhos of NADH?
- NADH dehydrogenase (I)
- Q (ubiquinone)
- Q-cytochrome C oxidoreductase (III)
- Cytochrome C
- Cytochrome C oxidase (IV)
- O2 —> H2O
What are the 5 steps in the OxPhos of FADH2?
- Succinate dehydrogenase (II)
- Q (ubiquinone)
- Q-cytochrome C oxidoreductase (III)
- Cytochrome C
- Cytochrome C oxidase (IV)
- O2 —> H2O
What are the 2 parts of ATP synthase and where do they lie?
- F0 —> membrane-bound
- F1 —> projects into matrix
Which 3 subunits does the F0 subunit consist of?
a, b, c
Which 3 subunits does the F1 subunit consist of?
a, b, g
How can ATP synthase both synthesis and hydrolyse ATP?
- F1 rotates clockwise —> H+ into matrix —> ATP synthesised
- F1 rotates anticlockwise —> H+ into intermembrane space —> ATP hydrolysed
- rotations direction controlled by F0
How is OxPhos measured in a lab?
Oxygen electrode
What is the cathode and anode of an oxygen electrode?
- Platinum cathode
- Silver anode
What reaction occurs at the cathode of an oxygen electrode?
O2 + 4H+ + 4e- —> 2 H2O
What reaction occurs at the anode of an oxygen electrode?
4 Ag + 4 Cl- —> 4 AgCl + 4e-
Label the 5 features of the [O2] against time graph for an oxygen electrode measuring OxPhos? (Draw)
- Start 0.25 mM
- Basal respiration —> shallow fall
- ADP added
- Oxidative Phosphorylation —> steep fall
- ADP consumed —> shallow fall
- O2 consumed —> 0mM
What are the 6 metabolic poisons affecting OxPhos and where do they act?
- Rotenone —> NADH dehydrogenase (I)
- Malonate —> Succinate dehydrogenase (II)
- Cyanide —> Cytochrome C oxidase (IV)
- Azide —> Cytochrome C oxidase (IV)
- Oligomycin —> ATP synthase
- DNP —> across inner membrane
How do cyanide and azide act as metabolic poisons?
CN- and N3- bind to Fe3+ of complex IV (high affinity)
—> block e- flow
How does malonate act as a metabolic poison?
-Similar structure to succinate —> binds to complex II —> competitive inhibitor
How does DNP act as a metabolic poison?
Transport H+ across inner mitochondrial membrane
—> bypasses ATP synthase —> no ATP generated
Which natural physiological process does DNP mimic?
Non-shivering thermogenesis
- drop in core temp (eg. in newborns) —> UCP-1 added to membranes —> H+ can bypass ATP synthase —> energy dissipates as heat —> inc core temp
How does rotenone act as a metabolic poison?
Block transfer of e-s from complex I to Q
How does oligomycin act as a metabolic poison?
Binds to ATP synthase stalk —> inhibits ATP synthesis
- Antibiotic
