From the Guidelines
The TCA cycle consists of a series of chemical reactions that occur in the mitochondria of cells to generate energy, with the steps including citrate formation, conversion to isocitrate, oxidation to α-ketoglutarate, decarboxylation to succinyl-CoA, conversion to succinate, oxidation to fumarate, hydration to malate, and finally oxidation to oxaloacetate. The TCA cycle, also known as the Krebs cycle or citric acid cycle, is a crucial process by which cells generate energy. According to a study by Shiraishi and Savageau 1, the TCA cycle can be modeled using canonical models, which have been shown to be useful in understanding the dynamics of biochemical and metabolic systems. The cycle begins when acetyl-CoA, derived from pyruvate oxidation, enters the cycle by combining with oxaloacetate to form citrate. This reaction is catalyzed by citrate synthase. Some key steps of the TCA cycle include:
- Citrate is converted to isocitrate by aconitase
- Isocitrate is then oxidized to α-ketoglutarate by isocitrate dehydrogenase, producing NADH
- α-Ketoglutarate is oxidatively decarboxylated to succinyl-CoA by α-ketoglutarate dehydrogenase, generating another NADH
- Succinyl-CoA is converted to succinate by succinyl-CoA synthetase, producing GTP (or ATP)
- Succinate is oxidized to fumarate by succinate dehydrogenase, producing FADH2
- Fumarate is hydrated to malate by fumarase
- Finally, malate is oxidized to oxaloacetate by malate dehydrogenase, producing another NADH. Each turn of the cycle produces three NADH, one FADH2, and one GTP/ATP, which are used in the electron transport chain to generate ATP through oxidative phosphorylation, as discussed in the study by Ni and Savageau 1.
From the Research
TCA Cycle Overview
The TCA (Tricarboxylic Acid) cycle, also known as the citric acid cycle, is a series of chemical reactions used to generate energy via the oxidation of acetylcoenzyme A (CoA) derived from carbohydrates, fatty acids, and proteins 2. It is the final common oxidative pathway for carbohydrates, fats, and amino acids and is the most important metabolic pathway for the energy supply to the body 3.
Steps of the TCA Cycle
The steps of the TCA cycle are as follows:
- The cycle begins with the conversion of acetyl-CoA to citrate
- Citrate is then converted to isocitrate
- Isocitrate is converted to alpha-ketoglutarate
- Alpha-ketoglutarate is converted to succinyl-CoA
- Succinyl-CoA is converted to succinate
- Succinate is converted to fumarate
- Fumarate is converted to malate
- Malate is converted back to oxaloacetate, which can then combine with another acetyl-CoA molecule to start the cycle again
Importance of the TCA Cycle
The TCA cycle is responsible for the complete oxidation of acetyl-CoA and formation of intermediates required for ATP production and other anabolic pathways, such as amino acid synthesis 4. It plays a crucial role in the regulation of immune responses and is involved in the regulation of cellular processes 2.
Key Intermediates and Enzymes
Key intermediates of the TCA cycle include citrate, isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, and malate. The initial and rate-limiting enzyme of the TCA cycle is citrate synthase (cts-1) 4. Other important enzymes include isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and succinyl-CoA synthetase.
Regulation and Energetics
The TCA cycle is regulated by various mechanisms, including feedback inhibition, allosteric control, and transcriptional regulation 3. The energetics of the TCA cycle involve the production of ATP, NADH, and FADH2, which are then used to generate energy for the cell 3.