Lecture #29 - CAC Flashcards
- Where does the CAC occur? (all but one…..)
- How many number of turns per molecule of glucose?
- How many number of turns per molecule of acyl FA?
- Basically, you capture energy in….
- What does the first half of the CAC do?
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First step in CAC: condensation
Explain
Okay so oxaloacetate and acetyl coA join together to form citrate and the energy for this condensation reaction comes from the cleaving of the bond between CoA and acetyl group. In this, CoA-SH is released. The overall G is negative indicating that it’s favourable
Second steps a and b CAC: dehydration
Explain
These steps are to form an isomer of citrate = isocitrate (the second step is dehydration and hydration)
a) Dehydration:
- take h20 away
b) Hydration:
- put it back
Use the enzyme aconitase (so same enzyme for both steps)
Basically rearrange to make next step of oxidative decarboxylation easier
Targeting the CAC to kill:
Explain
1080 and stuff have poison - sodium fluoroacetate
Fluoroacetate is metabolised to fluorocitrate and this binds and inhibits aconitase (so the conversion of citrate to isocitrate doesn’t happen)
This limits the ATP made and you die
Step Three: oxidative decarboxylation 1
Explain
This is where you have an oxidation occurring first (by isocitrate dehydrogenase) and form a reduced coenzyme NADH + H+ (so energy from the oxidation is conserved in NADH)
Then the decarboxylation happens and the removal of CO2 (i.e. equivalent of one of the carbons we added from acetyl coA at the start - needa lose so can get back to start molecule). So now isocitrate forms a five carbon alpha-ketogluterate
Step Five: oxidative decarboxylation 2
Explain
This is where the second carbon is removed and the molecule is oxidised (so NADH formed as a reduced coenzyme). The energy’s conserved as NADH.
This is catalysed by alpha-ketoglutarate dehydrogenase
The product is succinyl coA - four carbons
Form CO2 but add CoA to it!
Similar to pyruvate dehydrogenase reaction where under aerobic conditions, it also reduced NAD+ and removes CO2 and adds CoA to make acetyl coA
Summarise the main gist of the first and second half of CAC
First half is to do with energy being conserved in 2 NADH’s and two carbons were added and now they’re removed and we’ve ended up with a four carbon succinyl coA
The second half we wanna regenerate oxaloacetate (the starting point) from succinyl-CoA
Step 5: SLP
Explain
Turning succinyl-CoA to succinate and it’s like the activation of FA in reverse
The removal of CoA releases enough energy to drive the synthesis of GTP and GTP is a equivalent to ATP.
This is SLP because you’re coupling the breaking off of CoA to making GTP from GDP. Note how the P for this doesn’t come from the reactant. This is the 3rd SLP we’ve seen (first two were in glycolysis - used to make the ATPs)
Step 5, 6, 7 and 8: succinate to oxaloacetate
what happens
- First oxidation (dehydrogenation) and FAD reduced (probably also because FAD probably not strong enough oxidising agent
- Hydration where you add water across the double bond created by the oxidation
- Dehydrogenation again (oxidation) and NAD+ is used
A shared reaction: What is the one that is shared between CAC and ETC?
The succinate dehydrogenase reaction (step of dehydrogenation i.e. oxidation where FAD is reduced) is shared between CAC and ETC.
SDH is located in the inner mito mem and it’s part of complex 2 in ETC and FAD there too - FAD and SDH need to be together because (lecture 26) FAD are tightly bound to their enzymes (flavoproteins)
What’s the overall reaction?
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