The citric acid cycle is a crucial metabolic pathway that breaks down acetyl-CoA, producing energy and important molecules. It involves a series of reactions that release carbon dioxide, generate ATP, and create reduced electron carriers like NADH and FADH2.
This cycle is a key part of cellular respiration, connecting glycolysis to the electron transport chain. It occurs in the mitochondrial matrix of eukaryotes and the cytoplasm of prokaryotes, playing a vital role in energy production for cells.
Citric Acid Cycle Overview
Acetyl-CoA and Initial Reactions
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- Acetyl-CoA enters the citric acid cycle as a two-carbon molecule
- Acetyl-CoA combines with oxaloacetate (four-carbon molecule) to form citrate (six-carbon molecule)
- Citrate synthase catalyzes the condensation reaction between acetyl-CoA and oxaloacetate
- This reaction marks the first step of the citric acid cycle
- Citrate synthase releases coenzyme A and produces citrate
Carbon Dioxide Release and Energy Production
- The citric acid cycle releases two molecules of CO2 per acetyl-CoA
- CO2 release occurs during oxidative decarboxylation steps
- The cycle produces energy in the form of GTP (guanosine triphosphate)
- GTP can be converted to ATP through substrate-level phosphorylation
- The cycle also generates reduced electron carriers (NADH and FADH2)
Cycle Completion and Regeneration
- Oxaloacetate regenerates at the end of each cycle
- Regenerated oxaloacetate can combine with another acetyl-CoA molecule
- This regeneration allows the cycle to continue indefinitely
- The cycle occurs in the mitochondrial matrix of eukaryotic cells
- Prokaryotes perform the citric acid cycle in their cytoplasm
Oxidative Decarboxylation Steps
Isocitrate Dehydrogenase Reaction
- Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate
- This reaction converts isocitrate to α-ketoglutarate
- The process releases one molecule of CO2
- Simultaneously produces one molecule of NADH
- Isocitrate dehydrogenase requires NAD+ as a cofactor
α-Ketoglutarate Dehydrogenase Complex
- α-Ketoglutarate dehydrogenase complex catalyzes the next oxidative decarboxylation
- Converts α-ketoglutarate to succinyl-CoA
- Releases the second molecule of CO2 in the cycle
- Generates another molecule of NADH
- Requires thiamine pyrophosphate, lipoic acid, and NAD+ as cofactors
NADH Production and Electron Transport Chain
- The citric acid cycle produces a total of three NADH molecules per acetyl-CoA
- NADH serves as a high-energy electron carrier
- Transfers electrons to the electron transport chain
- Electron transport chain uses these electrons for ATP production via oxidative phosphorylation
- Each NADH can lead to the production of approximately 2.5 ATP molecules
Regeneration of Oxaloacetate
Succinyl-CoA to Succinate Conversion
- Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate
- This reaction produces GTP through substrate-level phosphorylation
- GTP can be converted to ATP by nucleoside diphosphate kinase
- Succinyl-CoA synthetase requires ADP or GDP as a phosphate acceptor
- This step marks the only substrate-level phosphorylation in the citric acid cycle
Succinate Oxidation and FADH2 Production
- Succinate dehydrogenase oxidizes succinate to fumarate
- This reaction reduces FAD to FADH2
- Succinate dehydrogenase anchored in the inner mitochondrial membrane
- FADH2 transfers electrons directly to the electron transport chain
- Each FADH2 leads to the production of approximately 1.5 ATP molecules
Final Steps and Oxaloacetate Formation
- Fumarase catalyzes the hydration of fumarate to malate
- Malate dehydrogenase oxidizes malate to oxaloacetate
- This final step produces another molecule of NADH
- Regenerated oxaloacetate can combine with a new acetyl-CoA to restart the cycle
- Malate dehydrogenase requires NAD+ as a cofactor