Lecture 27: Citric Acid Cycle Flashcards
Where in the cell does the citric acid cycle occur?
Occurs in the mitochondria
All but one of the enzymes is in the mitochondrial matrix
Carbon enters the citric acid cycle (CAC) in the form of acetyl-CoA, where does this acetyl-CoA come from?
Both glycolysis (aerobic, PDH reaction) and β-oxidation
produce acetyl-CoA in the mitochondria
What are the two major parts of the CAC?
- Release of C
- Regeneration of the starting molecule
Energy captured in both parts
How is energy captured in the CAC?
Making NADH and FADH₂, which carry high-energy electrons.
Producing a small amount of ATP (or GTP) directly.
These energy-rich molecules (NADH, FADH₂) are then used in the electron transport chain to make more ATP.
The first key reaction in the cycle is a condensation reaction, what is the product of this reaction and where does the energy for this reaction come from?
The product of this reaction is citrate (6C) from acetyl-CoA (2C) and oxaloacetate (4C)
Energy for the reaction comes from the hydrolysis of CoA from acetyl-CoA
The enzyme citrate synthase is responsible
What key events happen in an oxidative decarboxylation in the CAC?
Oxidation:
A molecule loses electrons, which are transferred to an electron carrier, specifically NAD⁺, forming NADH.
Decarboxylation:
A carboxyl group (–COOH) is removed from the molecule, and released as carbon dioxide (CO₂).
In the Citric Acid Cycle, oxidative decarboxylation occurs twice:
Isocitrate is oxidized and decarboxylated to form α-ketoglutarate, producing NADH and CO₂.
α-Ketoglutarate is oxidized and decarboxylated to form succinyl-CoA, also producing NADH and CO₂.
The conversion of succinyl CoA to succinate enables a substrate level phosphorylation. Describe what happens in a substrate level phosphorylation.
The DIRECT use of energy from a substrate molecule to drive the synthesis of ATP (or equivalent)
In the CAC the Succinyl-CoA has a high-energy thioester bond that is broken. This released energy drives the conversion of GDP ===> GTP (ATP) equivalent.
Does not involve the electron transport chain or oxygen.
The conversion of succinate to oxaloacetate is very similar to the reactions in which pathway?
The reactions used to convert succinate to
oxaloacetate are very similar to β-oxidation
(reactions 1,2,3)
What is the overall CAC reaction?
acetyl-CoA + 3NAD+ + FAD + 2H2O + GDP + Pi ➞
2CO2 + CoASH + 3NADH + 3H+ + FADH2 + GTP
Easier to read products:
3 NADH
1 FADH₂
1 GTP (or ATP)
2 CO₂ (carbon dioxide)
1 CoA (coenzyme A, regenerated)
CAC overall: ΔG0´= -44.3 kJ/mol
Pathway is energetically favourable
Heat also released
How does sodium fluoroacetate inhibit the CAC? i.e., after ingestion, what compound is it converted to and what component of the CAC does this inhibit?
After ingestion, sodium fluoroacetate is converted to fluoroacetyl-CoA which undergoes the condensation reaction with oxaloacetate to form fluorocitrate.
Fluorocitrate is converted into a substrate that binds tightly to aconitase and inactivates the enzyme
Inhibits the conversion of citrate to isocitrate in the Citric Acid Cycle (CAC). Hence the cycle can’t continue
Why is succinate dehydrogenase considered to be a shared enzyme?
Succinate dehydrogenase (SDH) is considered a shared enzyme because:
It is located in the inner mitochondrial membrane, functioning in both the Citric Acid Cycle (CAC) and the electron transport chain (ETC).
In the CAC, SDH uses FAD as a coenzyme to convert succinate to fumarate, reducing FAD to FADH₂.
As part of the ETC, SDH is needed to oxidize FADH₂ back to FAD, allowing it to continue participating in the CAC.
This dual role emphasizes SDH’s importance in linking the CAC and the ETC for efficient energy production.
What does the rearrangement of citrate to isocitrate allow?
Rearrangement of citrate to isocitrate makes the molecule
susceptible to decarboxylation
Both steps catalyzed by aconitase
Does the CAC start and finish with the same molecule?
Cycle: start and finish with the same molecule
Carbon enters and leaves
- 2 C in as acetyl-CoA
- 2 C out as 2 X CO2 (oxidation complete)
