The Citric Acid Cycle
The primary function of the citric acid cycle is to extract chemical energy from nutrients and store it in the form of adenosine triphosphate (ATP), the cell's primary energy source. The citric acid cycle, also known as the tricarboxylic acid cycle or Krebs cycle, is a vital biochemical process that occurs in the mitochondria of eukaryotic cells.
How does the citric acid cycle work?
Simply put, the citric acid cycle first takes in acetyl-CoA, which can come from the nutrients we eat. These nutrients (carbohydrates, fats, proteins) are digested and further broken down in various metabolic pathways (glycolysis, beta-oxidation, proteolysis) to ultimately form acetyl-CoA. This acetyl-CoA is then converted into a kind of starting material called citrate.
During the cycle, citrate goes through various stages, gradually transforming into other substances. Meanwhile, small energy molecules like NADH and FADH2 are generated. These molecules are like tiny batteries that are later used to produce ATP, the energy source for our cells
The Detailed Process
- Pyruvate + CoA → Acetyl-CoA: Pyruvate dehydrogenase is a multi-enzyme complex, located in the mitochondrion, requiring five coenzymes for complete catalysis: Thiamine pyrophosphate (TPP), lipoic acid, Coenzyme A, FAD, NAD+
- Acetyl-CoA + Oxaloacetate → Citrate: Enzyme: Citrate synthase, Co-substrate: H2O, Byproduct: Coenzyme A (CoA-SH)
- Citrate → Isocitrate: Enzyme: Aconitase
- Isocitrate → α-Ketoglutarate: Enzyme: Isocitrate dehydrogenase, Co-substrate: NAD+
- α-Ketoglutarate → Succinyl-CoA: α-Ketoglutarate dehydrogenase, similar to pyruvate dehydrogenase, requires cofactors including thiamine pyrophosphate, lipoamide, Coenzyme A, FAD, and NAD+. This step generates CO2 and an additional NADH+H+ for the respiratory chain.
- Succinyl-CoA → Succinate + CoA + GTP: Enzyme: Succinyl-CoA synthetase, Co-substrate: GDP, Pi
- Succinate → Fumarate + FADH2: The FAD-dependent succinate dehydrogenase, anchored in the inner mitochondrial membrane, oxidizes succinate to fumarate, releasing 1 FADH2.
- Fumarate + H2O → Malate: Enzyme: Fumarase
- Malate → Oxaloacetate: Enzyme: Malate dehydrogenase, Co-substrate: NAD+
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What happens to NADH and FADH2?
After the citric acid cycle is complete, NADH and FADH2 carry the energy stored during the cycle to contribute to ATP synthesis. These molecules act as "energy carriers," providing the main sources of electrons and protons for the electron transport chain (ETC) in the mitochondria.
Electron Transport Chain (ETC): NADH and FADH2 donate their electrons to the protein complexes of the ETC, located in the inner mitochondrial membrane. These electrons travel through a series of protein complexes, pumping protons (H+) from the mitochondrial matrix into the intermembrane space.
Proton pumps and electron transport: As electrons travel through the protein complexes, the energy generated by these proton pumps is used to actively pump protons into the intermembrane space, creating a proton gradient across the inner mitochondrial membrane.
ATP synthesis: The proton gradient is utilized by an enzyme called ATP synthase to produce ATP. ATP synthase acts as a "turbine," spinning as protons flow through it, converting ADP to ATP.
Water formation: At the end of the electron transport chain, electrons and protons combine with oxygen (O2) to form water (H2O). Regeneration of NAD+ and FAD:
The electrons traveling through the electron transport chain are transferred to oxygen, and NADH and FADH2 are regenerated to their original state (NAD+ and FAD). This is crucial because NAD+ and FAD are needed again in the citric acid cycle to continue the cycle.
In summary, NADH and FADH2 carry the energy stored during the citric acid cycle to the electron transport chain, generating ATP, which functions as the main energy currency of the cell. The process ends with the formation of water and the regeneration of the molecules NAD+ and FAD, which can be reused at the beginning of the citric acid cycle.