The Krebs cycle occurs in the mitochondrial matrix.
Prerequisites: Glycolysis and pyruvate decarboxylation to Acetyl CoA.
Key process: Converts Acetyl CoA to CO2 and H2O, producing energy-rich compounds.
Steps of the Krebs Cycle
1. Formation of Citrate
Reactants: Acetyl CoA and oxaloacetate
Enzyme: Citrate synthase
Products: Citrate, CoA (released), and consumption of one water molecule
2. Conversion to Isocitrate
Process: Citrate is isomerized to cis-aconitate and then to isocitrate
Enzyme: Aconitase
3. Formation of α-Ketoglutarate
Reactant: Isocitrate
Enzyme: Isocitrate dehydrogenase
Intermediate: Oxalosuccinate
Products: NADH, CO2 (first CO2 in the cycle), and α-ketoglutarate
Significance: Rate-limiting step, irreversible
4. Conversion to Succinyl CoA
Reactant: α-Ketoglutarate
Enzyme: α-Ketoglutarate dehydrogenase complex
Products: Succinyl CoA, NADH, CO2 (second CO2 in the cycle)
Cofactors Required: Thiamine pyrophosphate, lipoic acid, FAD, NAD, CoA
Regulation: Inhibited by ATP, GTP, NADH, succinyl CoA; Activated by calcium
5. Formation of Succinate
Reactant: Succinyl CoA
Enzyme: Succinyl CoA thiokinase
Products: Succinate, GTP (via GDP + phosphate), CoA (released)
6. Conversion to Fumarate
Reactant: Succinate
Enzyme: Succinate dehydrogenase
Products: FADH2 and fumarate
Significance: Enzyme also part of Electron Transport Chain (ETC) Complex II
7. Formation of Malate
Reactant: Fumarate
Enzyme: Fumarase
Products: L-Malate (consumes one water molecule)
8. Regeneration of Oxaloacetate
Reactant: L-Malate
Enzyme: Malate dehydrogenase
Products: NADH, Oxaloacetate
Significance: Coupled with the subsequent step (formation of citrate) to proceed due to energy considerations (Gibbs Free Energy)
Additional Points
Regulation and Feedback
Citrate synthase: Activated by ADP, inhibited by ATP, NADH, succinyl CoA
Citrate: Inhibits Phosphofructokinase (PFK), leading to feedback inhibition of glycolysis
Energy Production
Per Acetyl CoA, Krebs Cycle produces:
3 NADH
1 FADH2
1 GTP
Importance: Sets up the Electron Transport Chain for significant ATP production
Intermediates as Amino Acids
Oxaloacetate: Can be converted to aspartate
Alpha-Ketoglutarate: Can be converted to glutamate (and vice versa)
Role of Oxygen
Oxygen must be present to regenerate NAD+ and FAD from NADH and FADH2 for the cycle to proceed.
Summary
The Krebs Cycle is a crucial metabolic pathway for energy production, feeding into the Electron Transport Chain.
No significant ATP is produced directly by the cycle, but it generates high-energy electron carriers (NADH, FADH2) that are essential for ATP generation in the ETC.