30 Flashcards
Acetyl-CoA
Structure
Other names of cytric acid cycle (CAC)
Also called the Tricarboxylic acid (TCA) Cycle or the Krebs Cycle
Where does the cytric acid occur
Occurs in the mitochondria
Where are the enzymes that carry out the CAC located
All but one enzymes is in the mitochondrial matrix
CoA is already in the
Mitochondral matrix
Cytric acid starts and finishes with
The same molecule - CoA
Carbon ____ and ____ the cytric acid cycle… what do the two C enter as?
Carbon enters and leaves the cytric acid as acetyl-CoA
Where does acetyl-CoA come from?
Both glycolysis (aerobic, PDH reaction) and β-oxidation produce acetyl-CoA in the mitochondria
Carbons in the citric acid cycle
Carbon enters and leaves
- 2 C in as acetyl-CoA
- 2 C out as 2 X CO2
(oxidation complete)
Captures energy: - 1 ATP - 3 NADH and 1 FADH2
Citric acid cycle - first part involves …
- Release of C
Citric acid cycle - second part involves …
Regeneration of the starting molecule
Energy is captured in ______ parts of the cytric acid cycle
Both
Condensation of acetyl- CoA with oxaloacetate
2 C entering the CAC as acetyl-CoA is attached to 4 C oxaloacetate to produce 6 C citrate
Energy for the reaction comes from the hydrolysis of CoA from acetyl-CoA - energetically favourable - ΔG0´= -32.8 kJ/mol
Because the CAC is a “cycle” these two carbons need to be removed
Isomerisation of citrate
Rearrangement of citrate to isocitrate makes the molecule susceptible to decarboxylation
Both steps catalyzed by aconitase
Isomerisation of citrate - both reactions are catalyzed by
aconitase
Targeting the CAC to kill …
What happens when we consume fluoroacetate ?
- Fluoroacetate is metabolised to fluorocitrate
- reaction that adds acetyl-CoA
- instead of an H there is an F
- citrate snythase can tell the difference so it gets added to oxaloacetate
Isomerisation of citrate - FLUOROACETATE
Rearrangement of citrate to isocitrate makes the molecule susceptible to decarboxylation
Both steps catalysed by aconitase
Fluorocitrate is converted into a substrate that binds tightly to aconitase and inactivates the enzyme
Consequences of inhibiting the CAC
- increased acetyl-CoA (build up of acetyl CoA, increase dalta G values till it reaches unfavourable kenetically and then other processes such as B oxidation also wont be happening - YAP)
- decreased reduced coenzymes
- less ATP
Removal of the 1st carbon
- An oxidative decarboxylation
- Reaction occurs in two steps: oxidation then
decarboxylation - Energy captured in NADH
Isocitrate dehydrogenase used
Enzyme involved in the Removal of the 1st carbon
Isocitrate dehydrogenase
Removal of the 2nd carbon
- A second oxidative decarboxylation
- Very similar to the pyruvate dehydrogenase reaction - complex
- Energy captured in NADH
Adding on a
Enzyme = α −ketoglutarate dehydrogenase
ΔG0 ´= -33.4 kJ/mol
Citric Acid Cycle: Summary one part
- two carbons removed
- energy conserved as NADH
- a 4C molecule has been regenerated (succinyl-CoA)
The rest of the cycle is concerned with regenerating oxaloacetate and capturing more energy
Succinyl-CoA to succinate
The removal of the CoA releases enough energy to drive the synthesis of GTP
GTP is the energy equivalent of ATP:
- GTP + ADP <===> GDP + ATP
The 3rd substrate level phosphorylation (in pathways)
Substrate-level phosphorylation
- where does the phosphate come from
- doesnt matter - can come from the substrate like in glycolysis or come from solution in Succinyl-CoA to succinate
Succinate to oxaloacetate
Succinate to oxaloacetate - what is it simlat to?
The reactions used to convert succinate to oxaloacetate are very similar to β-oxidation
A shared reaction
- succinate —-> fumarate
SDH is located in the inner mitochondrial membrane
SDH uses FAD as a coenzyme: flavin (FAD) coenzymes are tightly bound to the proteins with which they interact (flavoproteins)
SDH is part of CAC where FAD is reduced, so needs to also be in the electron transport chain (ETC) to oxidize FADH2 back to FAD (- electron transport chain is in the inner mitochondrial membrane Hanse why SDH is located there)
succinate + E-FAD ➞ fumarate + E-FADH2
Overall reaction for the CAC
Overall reaction for the CAC