22. Mitochondrial details Flashcards
Oxidative phosphorylation proteins are located in the .. of the …
IM of the mito
ATP synthetase is which protein on the membrane? (1-5)
ATP is synthesized in 1 of mito’s, with H+ gradient in 2. However, most ATP
is needed in 3. They need to be shuttled out by specific 4
1 Matrix
2. IMS
3. Cytosol
4. ATP antiporter (VDAC)
Anti- vs symporter?
Antiporter: one thing goes out, one thing goes in (ADP out, ATP in)
Symporter: both out/in
There is also another symporter located at the ATP site, what does it do?
- Another symporter transports phosphate inside matrix together with protein. Phosphate needed to make ATP.
Transport of reducing equivalents (NADH) from 1 into 2 by 3 at the cost of 4
1 cytoplasm
2. mito
3. glycerophosphate shuttle.
4 Loss of 1 ATP: NADHc(2.5) -> FADHm (1.5)
Where is the glycerophosphate shuttle located? What is useful about this?
Glycerophosphate shuttle in mito: happens in intermembrane space. Not matrix of mito’s.
Fadh released very close to IMM. Will donate energy from NADH, now FADH directly to co-enzyme Q (CoQ)
Does every NADH get shuttled from cytoplasm into mito by glycerophosphate shuttle? Explain
this does not happen in every tissue like this. This one is very specific. Only for skeletal muscle and brain.
How much H+ = 1 ATP?
4 H+ = 1 ATP
When NADH (not FADH) is released to ox phos, this will come to complex A of ox phos, then to B (which is C), then to D , …
A 1
B 2
C (co enzyme Q)
D 3
Cost of glycerophosphate shuttle?
NADH -> FADH, so 2.5-1.5 = 1 ATP
What is useful about cristae?
seems like the complexes are in here, with specific efficient locations. Small location, high accumulation H+.
In what processes does FADH production happen?
FADH: production in
- TCA cycle (succinate -> fumarate. Succinate dehydrogenase, is also in complex 2)
- glycero-P shuttle
- beta-oxidation.
Why will FADH in ox phos lead to less energy than NADH?
FADH always donates energy to Co-enzyme Q! Never complex 1. This is why FADH will lead to less ATP production than NADH. Protons are not pushed out in this case by complex 1.
Which complexes push out protons?
1,3,5
What other shuttle system is there (not in skeletal muscle and brain)? Where is it highly active?
more complex shuttle system in tissues other than skeletal muscle and brain: Malate-aspartate shuttle
Active in
- Liver
- Kidney
- Heart
- Adipose
What happens with the malate-aspartate shuttle (use meta map)?
Everytime a 1 enters the mito, 2 is shuttled outside
Everytime an 3 leaves the mito, a 4 enters
They are reused in the cycle.
- Cytosol: OAA > Malate
- Malate enters mito
- Malate > OAA (+1NADHm: 2.5 ATP)
- OAA > aspartate
- Aspartate leaves mito into cytosol
- Cytosol: Aspartate > OAA
- Cytosol: OAA > aspartate
1 Malate
2 alfa-keto glutarate
- Aspartate
- glutamate
What is the main difference between the two shuttles?
Malate- asp: NADHc = NADHm
Glyceroph: NADHc = FADHm
1 more ATP remained at malate-asp
1 less ATP at glyceroph
1 ATP difference
Why is malate asp not used in brain if it is so efficient?
= constant rate of heat generation. Less ATP obtained with glyc-3-p shuttle, but constant heat, which is important in these tissues.
Difference full glucose ox with malate asp vs glyceroph shuttle?
Full glucose ox = 30 ATP
Malate/asp = 32 ATP
2 NADHc that needs to enter mito -> 3 ATP (2 FADH) (bc 2x pyruvate: OAA > malate, then malate outside mito)
2 NADHc that needs to enter mito -> 5 ATP (2 NADH)
Gluconeogenesis: pyruvate > OAA > malate out of mito into PEP.
There is another pathway used when there is a lot of pyruvate. Lot of lactate
Explain
Lactate leads to NADH in the cytosol. Lactate -> pyruvatec > pyruvate m > OAA.
OAA is then directly converted into PEPm > Pepc. No NADHm used, some energy is saved.
Choice for gluconeogenesis pathway depends on ..?
- Amount mito NADH (lot = original pathway)
- Pyruvate in cyto (lot = NADH-saving pathway)
In the liver, gl-6-p can be converted into glucose. When in the cytosol, there would be competition with the enzyme that catabolizes glucose -> gl-6-p. Therefore …
Therefore, enzyme that converts gl-6-p to glucose is present in the ER. When liver wants to release glucose, there is endocytosis: glucose will immediately go into blood circulation.
Compartments important!
ATP transport mito’s: from 1 to 2, also here certain enzymes (hexo/glucokinase, glycerolkinase) they are very close to the 3. Immediately use ATP for glucose trapping
1 OM
2 IM
3 ATP transporter
