Krebs Cycle

Krebs Cycle

The Krebs Cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a central metabolic pathway that occurs in the mitochondrial matrix of eukaryotic cells. It plays a crucial role in the breakdown of carbohydrates, fats, and proteins, producing energy-rich molecules such as NADH and FADH₂ that feed into the electron transport chain for ATP synthesis. Let's go through the Krebs Cycle with its chemical reactions:


1. Acetyl-CoA Formation:

   - Before entering the Krebs Cycle, pyruvate, a product of glycolysis, is converted into acetyl-CoA in the mitochondrial matrix. This reaction is catalyzed by the enzyme pyruvate dehydrogenase.


   - Chemical reaction:

     - Pyruvate + CoA + NAD⁺ → Acetyl-CoA + NADH + CO₂


2. Citrate Formation:

   - Acetyl-CoA combines with oxaloacetate, a four-carbon compound, to form citrate, a six-carbon compound. This reaction is catalyzed by the enzyme citrate synthase.


   - Chemical reaction:

     - Acetyl-CoA + Oxaloacetate → Citrate + CoA


3. Isocitrate Formation:

   - Citrate is isomerized into isocitrate through the removal of a water molecule. This reaction is catalyzed by the enzyme aconitase.


   - Chemical reaction:

     - Citrate → Isocitrate + H₂O


4. Alpha-Ketoglutarate Formation:

   - Isocitrate undergoes oxidative decarboxylation, resulting in the formation of alpha-ketoglutarate and the release of CO₂ and NADH. This reaction is catalyzed by isocitrate dehydrogenase.


   - Chemical reaction:

     - Isocitrate + NAD⁺ → Alpha-Ketoglutarate + CO₂ + NADH


5. Succinyl-CoA Formation:

   - Alpha-ketoglutarate is further decarboxylated, producing succinyl-CoA, CO₂, and another NADH molecule. This reaction is catalyzed by alpha-ketoglutarate dehydrogenase.


   - Chemical reaction:

     - Alpha-Ketoglutarate + NAD⁺ + CoA → Succinyl-CoA + CO₂ + NADH


6. Succinate Formation:

   - Succinyl-CoA undergoes a substrate-level phosphorylation reaction, transferring a phosphate group to ADP to form ATP and yielding succinate. This reaction is catalyzed by succinyl-CoA synthetase.


   - Chemical reaction:

     - Succinyl-CoA + ADP + Pi → Succinate + ATP + CoA


7. Fumarate Formation:

   - Succinate is oxidized to form fumarate, with the concurrent reduction of FAD to produce FADH₂. This reaction is catalyzed by succinate dehydrogenase, which is a part of the inner mitochondrial membrane and also a component of the electron transport chain.


   - Chemical reaction:

     - Succinate + FAD → Fumarate + FADH₂


8. Malate Formation:

   - Fumarate is hydrated to form malate. This reaction is catalyzed by fumarase.


   - Chemical reaction:

     - Fumarate + H₂O → Malate


9. Oxaloacetate Regeneration:

   - Malate is oxidized to regenerate oxaloacetate, accompanied by the reduction of NAD⁺ to NADH. This reaction is catalyzed by malate dehydrogenase.


   - Chemical reaction:

     - Malate + NAD⁺ → Oxaloacetate + NADH


The Krebs Cycle completes one turn for each acetyl-CoA entering the cycle. Since two acetyl-CoA molecules are produced from each glucose molecule during glycolysis, two turns of the Krebs Cycle occur per glucose molecule, generating multiple NADH, FADH₂, and ATP molecules in the process. The energy-rich products, NADH and FADH₂, then participate in oxidative phosphorylation in the electron transport chain, leading to the production of ATP.


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