MITOCHONDRIAL PHYSIOLOGY Flashcards
4 main functions of the mitochondria
- ATP production
- apoptosis
- calcium storage
- non shivering thermogenesis
by which 2 mechanisms is ATP produced
- substrate level phosphorylation
- oxidative phosphorylation
what happens in glycolysis
glucose-2 pyruvate + 2NADH + 2ATP
what happens in pyruvate oxidation
pyruvate-acetyl coA + NADH
What is produced in the krebs cycle
- 6 NADH (2 rounds)
- 2 FADH
- CO2
4.2ATP
how many ATP are produced from oxidative phosphorylation
- 1 NADH molecule can produce 2.5 ATP
- 1 FADH molecule can produce 1.5 ATP
- so 10x2.5= 25
- 2x1.5=3
=28 ATP
how many ATP produced in total
-28 from oxidative phosphorylation
-2 from glycolysis
-2 from krebs cycle
=32 ATP
how is this number influence by the shuttle mechanism used
- because if FADH brings the NADH from glycolysis across into the mitochondria =1.5 atp but if NADH brings it across this = 2.5
- so 1.5 x2=3
-so 2.5x 2=5
therefore either 30 or 32 ATP in total
explain the steps of oxidative phosphorylation
- NADH brings electrons to PC1 and donates them to flavomononucleotide
- from here they are passed through ion centers where they are finally given off to ubiquinone =ubiquinol
- movement of electrons pumps 4 H + ions across the membrane
- then ubiquinol will move to PC3 and give off its electrons to cytochrome C
- this movement pumps 4H+ from PC3 into the intermembrane space
- then CYT C will migrate to PC4 and donate electrons to oxygen to form water. this movement pumps 2H+ ions into the intermembrane space from PC4
= 10H+ ions from 1 NADH molecule - then FADH donates its electrons to PC2 to ion centers.
- this passes electrons to ubiquinone= ubiquinol
- the movement of ubiquinol to PC3 to donate electrons to CYT C then generates those same 4 H+ from PC3
- process is now the same
= 6H+ from 1 FADH
what are the 2 shuttle mechanisms used
- glycerol phosphate - brown adipose tissue, plants and fungi
- malate aspartate - rest of your body cells
explain how the glycerol phosphate mechanism works
here glycerol 3 phosphate travels from the cytosol into the mitochondria where it is oxidised to DHAP so it can give its electrons to FAD to form FADH
= 1.5 ATP produced when the glycerol phosphate shuttle is used
-the DHAP is then shuttled back into the cytosol
explain how the malate aspartate shuttle works
L-aspartate will be converted into oxaloacetate in the cytoplasm and then into malate. oxaloacetate to malate oxidises NADH to NAD+
- then malate shuttles into the matrix and is oxidised to oxaloacetate so malate can donate electrons to NAD+= NADH
=2.5 ATP
-the oxaloacetate converted to L-aspartate which goes back into the cytosol
what is non shivering thermogenesis in the mitochondria
this process makes use of the fact that phosphorylation and oxidation(ET) are tightly coupled
- so electrons wont flow to oxygen if ATP is not produced and ATP will not be produced if oxygen is not being consumed
inhibiton of oxidative phosphorylation
if something blocks any step in the process
- we will see oxygen consumption stops and ATP
inhibiton of oxidative phosphorylation
if something blocks any step in the process
- we will see oxygen consumption stops and ATP production stops
uncoupling of oxidative phosphorylation
- O2 consumption will continue but ATP synthesis will stop
-this is because of some leakage allowing H+ ions to exit the intermembrane space and dissipate the gradient without going through ATP synthase
-so the ETC tries to fix this dissipated gradient by speeding up ETC so more O2 is consumed and so need to recycle NADH and FADH faster and so krebs cycle speeds up so CO2 production increases which increases respiration and basal metabolic rate
what are the different uncoupled states
- tightly coupled- ET is tightly coupled to phosphorylation
2.partially uncoupled-normal physiological conditions to generate heat via UCP - dys coupled respiration- toxicological or pathological process in mitochondrial dysfunction
- uncoupled respiration-induced in experiments to determine someones respiratory capacity
chemical uncouplers
- 2,4-DNP
- CCCP
3.FCCP
physiological uncouplers
- thermogenin
- thyroxin
explain the process of physiological uncoupling using thermogenin to generate heat
- the hypothalamus detects the cold and releases norepinephrine
- the norepinephrine then binds to beta adrenergic receptor on the BAT membrane
- this sheds an active G protein which can bind to adenylate cyclase and activate it
- adenylate cyclase stimulates the conversion of ATP to cAMP
5.cAMP then activates protein kinase - protein kinase activates lipase
7.lipase then breaks down triglycerides into FFAs - The increase in FFAs stimulates thermogenin
=heat produced
what is the difference between apoptosis and necrosis
NECROSIS
-unplanned sponatenous cell death
-causes harm to neighbouring cells
-can lead to an inflammatory response
APOPTOSIS
-planned cell death of damaged/infected cells
-also necessary in development of fingers and toes
what are the 3 mechanisms of apoptosis
- intrinsic pathway
- extrinsic pathway
- AIF
- intrinsic pathway
the cell damage stimulates BAX to be released which binds to BCL-2 so it can no longer inhibit apoptosis
-then apaf-2 binds with cytC to produce apoptosome
-the apoptosome then activates caspase 9 which initates apoptosis
- the extrinsic pathway
upon cell damage; the death receptor on the damaged cell will bind to a death activator on an immune cell so as to activate caspase 8 in the damaged cell to initiate apoptosis
apoptosis inducing factor pathway
upon damage; AIF is released from the mitochondrial intermembrane space; into cytoplasm where it moves the nucleus to bind and destroy the DNA of the damaged cell
explain how mitochondria aid in calcium storage
calcium is found in very low concentrations in the cytoplasm because otherwise it would bind with proteins and cause conformational changes to expose the hydrophobic regions of the proteins which will make them insoluble
- so only found in high concentration in certain areas like near the ER
- here the calcium levels are higher than in the mitochondria
through what transport system does calcium move through to enter the mitochondria
MCU- mitochondrial calcium uniporter
-it has 2 subunits each with 2 polypeptides
-bound by MICU1 and MICU2 proteins that have EF hands
explain what happens when the calcium levels are higher in the cytoplasm than in the mitochondria
- at low concentrations of calcium in the cytoplasm the MICU1 and 2 proteins remain bound to MCU
-then at high concentrations the following happens:
1. calcium will bind to the MICU1 EF hands so MICU1 can activate MCU
2. calcium will also bind to the MICU2 EF hands to stop MICU2 from inhibiting MCU
3. so MCU opens and calcium can flow into the mitochondria
