In the CAC, the acetyl molecule is ultimately oxidized to what?
CO2
What amount of the total ATP produced in the body is made in CAC
2/3
Also most of the CO2 we exhale is from the CAC
Which reaction #s are oxidation/reduction reactions?
3, 4, 6, 8
3,4 = oxidative decarboxylation (CO2 is removed)
Which reaction is a substrate-level phosphorylation reaction
5
Producing GTP
The CO2 produced in the CAC come originate from what molecule?
OAA (not Ac-CoA)
2 total
Citrate synthase
Ac-CoA is condense with OAA —> citrate
CoA group is removed…hydrolysis of thioester bond between carbon and sulfur group
Irreversible
Inhibited by product feedback (citrate)
Recall: citrate also inhibitor of glycolytic PFK-1 enzyme
Aconitase
Citrate —> isocitrate
Isomerization of C-3 OH group —> C-5 position
Reversible
Cis-aconitate = intermediate
1st step = dehydration
2nd step = hydration
Isocitrate dehydrogenase
Isocitrate —> alpha-ketoglutarate
Makes CO2 and NADH
Irreversible
Alpha-KG dehydrogenase complex
A-KG —> succinyl-CoA
Makes NADH and CO2
Mechanically similar to PDH complex
—> needs SAME vitamin cofactors!
Irreversible
Succinyl-CoA synthetase
Substrate-level phosphorylation
Succinyl-CoA —> succinate
- Breaks thioester bond in succinyl-CoA
—> succinyl phosphate intermediate - Phosphate group is transferred to the enzyme —> liberating succinate
- High energy phosphate group is transferred to GDP —> GTP
Irreversible
Succinate dehydrogenase
Succinate —> Fumarate
Makes FADH2
This enzyme is associated with the inner membrane of the mitochondria
Therefore, the electrons can be fed directly into the e-transport chain
Reversible
Fumarase
Fumarate —> malate
Water is added across the double bond in fumarate to create a OH group in malate
Reversible
Malate dehydrogenase
Malate —> OAA
Makes NADH
Reversible
Yield of CAC
2 CO2
3 NADH = 3*2.5ATP = 7.5 ATP
FADH2 = 1.5 ATP = 1.5 ATP
GTP = 1 ATP
CoASH
TOTAL ATP = 10 ATP
Overally efficiency of CAC
Total amount of energy is Acetyl group = ~228 kcal/mole
Energy produced in CAC ~~ 207 kcal/mol
90% efficiency
Main type of CAC regulation
Allosteric regulation
Within mitochondria
Effect of ADP
Low-energy state
Stimulates reactions 3 and 4
Effect of NADH
As [NADH]»_space;» [NAD+] —> high energy state
Reactions 3, 4, and 8 = inhibited since NAD+ = a cofactor
NADH = most inhibitory effect on the pathway
Effect of Ca2++
Stimulates reactions 3 and 4
Same effect it did on the PDH complex
Much energy is used in muscle contraction and Ca2+ stores are released from the SER —> will stimulate CAC reaciton
Citrate regulation
Feed back inhibition on its own synthesis
By citrate synthase
Important CAC intermediates and what they are used for
- Citrate —> FAS and sterol formation
- A-KG —> converted to glutamate, which is used to make other aa and purine synthesis
- OAA —> converted to asparate, which is used to make other aa and purine/pyrimidine syn.
- Succinyl-CoA —> make porphyrins or heme
How CAC intermediates are replenished
- Pyruvate carboxylase rxn —> makes OAA from pyruvate
- A-Kg produced from glutamate
- Succinyl-CoA made from valine, isoleucine, or certin fatty acids
- Fumarate can be made from certain aa
- Asparate can replenish OAA also
How do reduced electron equivalents get from cytosol —> mitochondria
Gylcerol phosphate shuttle —> makes 1.5 ATP per shuttle
Malate-asparate shuttle —> makes 2.5
Glycerol phosphate shuttle
In the cytosol…glycerol 3-phosphate dehydrogenase oxidized NADH —> NAD+
At the same time…DHAP is reduced to glycerol-3P
At the IMM…G3P is reoxidized by membrane-bound G3P dehydrogenase back to DHAP
In matrix…those electrons reduce FAD —> FADH2
