Citric Acid Cycle Flashcards
What happens in the Link reaction, and why is it important?
Pyruvate in the cytosol enters the mitochondria and is converted into acyl-CoA by pyruvate dehydrogenase.
The Link reaction is important because it ‘links’ anaerobic glycolysis to aerobic metabolism in mitochondria.
Pyruvate + CoASH + NAD → Acetyl CoA + CO2 + NADH
This reaction is very exothermic and so it is regulated, but it is absolutely irreversible; there are no enzymes in the human body that can convert acetyl-CoA back into pyruvate.
How is isocitrate formed from oxaloacetate in the citric acid cycle?
1 → Acetyl-CoA and oxaloacetate react to form citrate, and this is catalysed by citrate synthase. Hydrolysis of the thioester bond provides the energy to form a C-C bond. This reaction has a very -ΔG, so the enzyme is regulated.
2 → Citrate is isomerised into isocitrate by aconitase; aconitase moves the hydroxyl group from C3 to C2 in order to make the COO- group easier to decarboxylate in the next step. This reaction has a very +ΔG, so it is compensated and driven forward by the previous reaction and the abundance of citrate.
How is isocitrate converted into succinate in the citric acid cycle?
1 → Isocitrate undergoes oxidative decarboxylation to form alpha-ketoglutarate, aided by the enzyme isocitrate dehydrogenase. This reduces NAD to NADH and forms CO2. This reaction has a very -ΔG, so the enzyme is regulated.
2 → Alpha-ketoglutarate undergoes oxidative decarboxylation, forming succinyl-CoA with the help of the enzyme alpha-ketoglutarate dehydrogenase. This reduces NAD into NADH and forms another CO2. This reaction also has a very -ΔG, so this enzyme is regulated (and is the last one in the cycle to be regulated).
3 → Succinyl-CoA is converted into succinate via succinyl-CoA synthetase. The hydrolysis of the thioester bonds provides the energy to phosphorylate ADP/GDP, forming ATP/GTP via substrate level phosphorylation. This reaction is reversible within the cell.
How is succinate turned back into oxaloacetate in the citric acid cycle?
1 → Succinate is oxidised into fumarate using the enzyme succinate dehydrogenase. This reduces FAD into FADH2 in the process. This forms a double bond between C2 and C3. ΔG = 0
2 → The double bond in fumarate is hydrated to form malate, which has a hydroxyl group on C2. The enzyme that catalyses this reaction is fumarase, and ΔG = -3.8
3 → Malate is oxidised into oxaloacetate using the enzyme malate dehydrogenase, which forms a C=O on C2. This also reduces NAD into NADH. This reaction has a very +ΔG, but it is compensated by the following reaction having a very -ΔG, as well as the fact that oxaloacetate is constantly being removed.
What is the yield of the citric acid cycle?
1 x CoASH
2 x CO2
3 x NADH = 7.5 ATP
1 x FADH2 = 1.5 ATP
10 ATP in total
What happens to the citric acid cycle in each metabolic state?
Fed → Glycolysis is increased, so acetyl-CoA comes from sugars
Fasting → Glycolysis is inhibited, so acetyl-CoA comes from fatty acid oxidation
Exercise → The citric acid cycle enzymes are stimulated, and acetyl-CoA supply is increased due to both increased glycolysis and fatty acid oxidation. The concentration of intermediates also increases.
