Tricarboxylic acid

A central metabolic pathway in cellular respiration

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 release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

Overview

The TCA cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy. It takes place in the mitochondrial matrix in eukaryotic cells and in the cytoplasm of prokaryotic cells. The cycle is named after Hans Adolf Krebs, who identified the cycle in 1937.

Function

The primary function of the TCA cycle is to produce high-energy electron carriers, NADH and FADH2, which are used in the electron transport chain to generate adenosine triphosphate (ATP), the energy currency of the cell. The cycle also provides precursors for various biosynthetic pathways.

Steps of the Cycle

The TCA cycle consists of eight main steps:

1. Citrate Formation: Acetyl-CoA combines with oxaloacetate to form citrate, catalyzed by the enzyme citrate synthase.
2. Isomerization to Isocitrate: Citrate is converted to isocitrate via aconitase.
3. Oxidative Decarboxylation of Isocitrate: Isocitrate is oxidized to _-ketoglutarate, producing NADH and releasing carbon dioxide (CO2), catalyzed by isocitrate dehydrogenase.
4. Oxidative Decarboxylation of _-Ketoglutarate: _-Ketoglutarate is converted to succinyl-CoA, producing NADH and releasing CO2, catalyzed by _-ketoglutarate dehydrogenase.
5. Conversion to Succinate: Succinyl-CoA is converted to succinate, producing GTP (or ATP) in the process, catalyzed by succinyl-CoA synthetase.
6. Oxidation of Succinate: Succinate is oxidized to fumarate, producing FADH2, catalyzed by succinate dehydrogenase.
7. Hydration of Fumarate: Fumarate is hydrated to malate, catalyzed by fumarase.
8. Oxidation of Malate: Malate is oxidized to regenerate oxaloacetate, producing NADH, catalyzed by malate dehydrogenase.

Regulation

The TCA cycle is tightly regulated by the availability of substrates and feedback inhibition. Key regulatory enzymes include citrate synthase, isocitrate dehydrogenase, and _-ketoglutarate dehydrogenase. High levels of ATP and NADH inhibit these enzymes, while ADP and NAD+ act as activators.

Clinical Significance

Defects in the TCA cycle can lead to various metabolic disorders. For example, mutations in the genes encoding TCA cycle enzymes can result in mitochondrial diseases. Additionally, the TCA cycle is a target for certain cancer therapies, as cancer cells often exhibit altered metabolism.

Images

File:Krebs cycle.svg

Diagram of the Krebs cycle showing the main steps and products.

File:Mitochondrion diagram en.svg

The TCA cycle occurs in the mitochondrial matrix.

Related Pages

• Glycolysis
• Electron transport chain
• Oxidative phosphorylation
• Metabolism