Tricarboxylic acid

Tricarboxylic Acid Cycle (TCA Cycle)

The Tricarboxylic Acid Cycle (TCA Cycle), also known as the Krebs Cycle or the Citric Acid Cycle, is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of Acetyl-CoA derived from carbohydrates, fats, and proteins into Carbon dioxide and Water. This process also generates Adenosine triphosphate (ATP), which is a major energy currency of the cell. The cycle is named after Hans Krebs, who identified the key components and their relationships in 1937, earning him the Nobel Prize in Physiology or Medicine in 1953.

Overview

The TCA cycle is a central component of the cellular metabolic pathway. Located in the mitochondrial matrix, it is the third stage of cellular respiration, following Glycolysis and the decarboxylation of pyruvate to Acetyl-CoA. The cycle is both anabolic and catabolic, playing a crucial role in the metabolic framework for the synthesis and breakdown of biomolecules.

Steps of the TCA Cycle

The TCA cycle involves eight main steps, each catalyzed by a specific enzyme:

1. The condensation of Acetyl-CoA with Oxaloacetate to form Citrate.
2. The isomerization of Citrate to Isocitrate via Aconitase.
3. The oxidative decarboxylation of Isocitrate to Alpha-Ketoglutarate, producing CO2 and NADH.
4. The oxidative decarboxylation of Alpha-Ketoglutarate to Succinyl-CoA, generating CO2, NADH, and ATP or GTP.
5. The conversion of Succinyl-CoA to Succinate, producing ATP or GTP.
6. The oxidation of Succinate to Fumarate, producing FADH2.
7. The hydration of Fumarate to Malate.
8. The oxidation of Malate to Oxaloacetate, producing NADH, thus completing the cycle.

Significance

The TCA cycle is crucial for cellular respiration, providing the majority of the energy used by aerobic organisms. It is also a source of precursors for many biosynthetic pathways, making it a hub for both energy production and the synthesis of key biomolecules.

Regulation

The TCA cycle is tightly regulated by the availability of substrates and feedback inhibition. Key regulatory enzymes include Citrate synthase, Isocitrate dehydrogenase, and Alpha-Ketoglutarate dehydrogenase. These enzymes are inhibited by high levels of ATP, NADH, and succinyl-CoA, ensuring that the cycle progresses in response to the cell's energy needs.

Clinical Significance

Abnormalities in the TCA cycle can lead to various metabolic disorders and have been implicated in the pathogenesis of cancer, neurodegenerative diseases, and diabetes. Understanding the TCA cycle's regulation and its role in disease is crucial for developing therapeutic strategies.

See Also

• Cellular Respiration
• Glycolysis
• Oxidative Phosphorylation
• Metabolic Pathway