Lecture 30: THE FINAL OXIDATION - CITRIC ACID CYCLE Flashcards
Where does the citric acid cycle occur?
In the mitochondria (matrix)
Where are the enzymes for the citric acid cycle found?
All but one are in the mitochondrial matrix
What is meant by the citric acid cycle being a cycle?
It starts and finishes with the same molecule
What does the carbon do in the citric acid cycle?
Enters as 2C in Acetyl-CoA and leaves as 2C in 2 CO2 (oxidation complete)
How is energy captured in the citric acid cycle?
1 ATP, 3 NADH and 1 FADH2
What are the parts of the citric acid cycle?
The first part is release of carbon and the second is regeneration of the molecule
What happens in both parts of the citric acid cycle?
Energy is captured
What happens in the condensation of acetly-CoA with oxaloacetate?
2C entering the citric acid cycle as acetyl-CoA are attached to 4C oxaloacetate to produce 6C citrate which requires energy
Where does the energy for the condensation of acetly-CoA with oxaloacetate come from?
The hydrolysis of CoA from Acetyl-CoA
What is the delta G for condensation of acetly-CoA with oxaloacetate?
-32.8 kJ/mol
What happens in the isomerisation of citrate?
Rearrangement of citrate to isocitrate (in a dehydration and hydration reaction) makes the molecule susceptible to decarboxylation
What are the steps of isomerisation of citrate catalysed by?
Aconitase
What is found in 1080?
Fluoroacetate
What happens with fluoroacetate?
It is metabolised to fluourocitrate
What is the first part of metabolising fluoroacetate to fluorocitrate?
Fluoroacetate + CoA»_space; fluoroacetyl -CoA
What can’t citrate synthase do?
Differentiate between fluoroacetly - CoA and acetyl- CoA so converts fluoroacetly - CoA to fluorocitrate
What happens with fluorocitrate?
It is converted to a substrate that binds tightly to aconitase and inactivates the enzyme, preventing isomerisation
What are the consequences of inactivating aconitase?
No CAC, an increased concentration of acetyl - CoA so decreased pyruvate dehydrogenase reaction, glycolysis and beta oxidation, also steps downstream of the CAC
What type of reaction is the removal of the first carbon?
Oxidative decarboxylation which occurs in two steps (oxidation then decarboxylation)
Where is energy captured in the removal of the first carbon?
In NADH
What catalyses the removal of the first carbon?
Isocitrate dehydrogenase catalyses both parts
What does the intermediate of the removal of the first carbon do?
(oxalasuccinate) remains enzyme bound
What type of reaction is the removal of the second carbon?
An oxidative decarboxylation very similar to the pyruvate dehydrogenase reaction
Where is energy captured in the removal of the second carbon?
NADH
What does the reaction removing the second carbon use?
An enzyme requiring lots of cofactors and coenzymes
What happens in the removal of the second carbon?
Deprotonated carboxyl group is cleaved and the energy is used to add CoA
What is the delta G for the removal of the second carbon?
-33.4 kJ/mol
What happens in the reaction of succinyl-CoA to succinate?
The removal of CoA releases enough energy to drive the synthesis of GTP
What is GTP?
The energy equivalent of ATP (GTP + ADP <> GDP + ATP). There is an increased GTP and ADP (because ATP is being used) which will drive the synthesis of ATP
What type of reaction is succinyl-CoA to succinate?
A substrate level phosphorylation
What happens in a substrate level phosphorylation?
The direct use of energy from a substrate molecule to drive the synthesis of ATP (or equivalent). The phosphate does need to come from the substrate (just the energy)
What are the reactions used to convert succinate to oxaloacetate similar to?
Beta oxydation (oxidation, hydration, oxidation)
Where is succinate dehydrogenase found?
In the inner mitochondrial membrane
What does SDH use as a coenzyme?
FAD
Where are flavin coenzymes found?
Tightly bound to the proteins with which they interact (flavoproteins)
What must happen with FADH2?
It must be oxidised back to FAD in the electron transport chain which occurs in the inner mitochondrial membrane
What is the equation for the SDH reaction?
Succinate + E-FAD»_space;> Fumarate + E-FADH2
What is the overall reaction for the citric acid cycle?
Acetyl - CoA + 3NAD+ + FAD + 2H2O + GDP + Pi»_space;> 2CO2 + CoASH + 3NADH + 3H+ + FADH2 + GTP
What is the delta G for the citric acid cycle?
-44.3 kJ/mol (energetically favourable)
