The Krebs Cycle (Citric Acid Cycle)
The Krebs cycle is a series of enzyme-catalyzed reactions that occur in the mitochondrial matrix. It plays
a central role in cellular respiration, oxidizing acetyl-CoA derived from carbohydrates, fats, and proteins
to produce energy carriers.
1. Citrate Formation:
o Acetyl-CoA (2 carbons) combines with oxaloacetate (4 carbons) to form citrate (6
carbons).
o Enzyme: Citrate synthase
o This reaction releases Coenzyme A (CoA).
o Acetyl−CoA + Oxaloacetate + H2O → Citrate + CoA
2. Isocitrate Formation:
o Citrate is isomerized to isocitrate.
o Enzyme: Aconitase
o This involves a dehydration followed by a hydration step.
3. α-Ketoglutarate Formation:
o Isocitrate is oxidized and decarboxylated (loss of CO2) to form α-ketoglutarate (5
carbons).
o Enzyme: Isocitrate dehydrogenase
o NAD+ is reduced to NADH.
o Isocitrate + NAD + → α−ketoglutarate + CO2 + NADH + H+
4. Succinyl-CoA Formation:
o α-ketoglutarate is oxidized and decarboxylated to form succinyl-CoA (4 carbons).
o Enzyme: α-ketoglutarate dehydrogenase complex
o NAD+ is reduced to NADH.
o CoA is added.
o α−ketoglutarate + CoA + NAD + → Succinyl−CoA + CO2 + NADH + H+
5. Succinate Formation:
o Succinyl-CoA is converted to succinate (4 carbons).
o Enzyme: Succinyl-CoA synthetase (or succinate thiokinase)
o GTP (or ATP in some organisms) is produced by substrate-level phosphorylation.
o Succinyl−CoA + GDP + Pi → Succinate + CoA + GTP
6. Fumarate Formation:
o Succinate is oxidized to fumarate (4 carbons).
o Enzyme: Succinate dehydrogenase (which is also part of the electron transport chain,
complex II)
o FAD is reduced to FADH2.
o Succinate + FAD → Fumarate + FADH2
7. Malate Formation:
o Fumarate is hydrated to malate (4 carbons).
o Enzyme: Fumarase (or fumarate hydratase)
o Fumarate + H2O→ Malate
8. Oxaloacetate Regeneration:
o Malate is oxidized to oxaloacetate (4 carbons), regenerating the starting molecule for the
cycle.
o Enzyme: Malate dehydrogenase
o NAD+ is reduced to NADH.
o Malate + NAD + → Oxaloacetate + NADH + H+
Key Outputs of the Krebs Cycle (per molecule of Acetyl-CoA):
2 CO2
3 NADH
1 FADH2
1 GTP (or ATP)
Significance:
The Krebs cycle is essential for cellular respiration, providing electrons (carried by NADH and FADH2)
for the electron transport chain, where the bulk of ATP is produced. It also generates important metabolic
intermediates used in other biosynthetic pathways.