Citric acid cycle
In biochemistry, the citric acid cycle, also called the Krebs cycle, the tricarboxylic acid cycle or the TCA cycle, is a series of chemical reactions of central importance in all living cellss that utilize oxygen as part of cellular respiration. In these aerobic organisms, the citric acid cycle is a metabolic pathway that forms part of the break down of carbohydrates, fats and proteins into carbon dioxide and water in order to generate energy. It also provides precursors for many compounds such as certain amino acids, and some of its reactions are therefore important even in cells performing fermentation.The Krebs cycle is named after Sir Hans Adolf Krebs (1900-1981), who was awarded the 1953 Nobel Prize in Medicine for its discovery.
The citric acid cycle takes place within the mitochondria in eukaryotes, and within the cytoplasm in prokaryotes.
The citric acid cycle forms part of carbohydrate catabolism, protein catabolism and fat catabolism. All these three processes produce acetyl-CoA, a two-carbon acetyl group bound to coenzyme A. Acetyl-CoA is the main input to the citric acid cycle.
Citrate is both the first and the last product of the cycle (Fig. 1), and is regenerated by the condensation of oxaloacetate and acetyl-CoA.
Figure 1 : Schematic drawing of the citric acid cycle.
| Molecule | Enzyme | Reaction Type | Reactants/ Coenzymes |
Products/ Coenzymes |
|---|---|---|---|---|
| I. Citrate | 1. Aconitase | Dehydration | H2O | |
| II. cis-Aconitate | 2. Aconitase | Hydration | H2O | |
| III. Isocitrate | 3. Isocitrate Dehydrogenase | Oxidation | NAD+ | NADH+H+ |
| IV. Oxalosuccinate | 4. Isocitrate Dehydrogenase | Decarboxylation | ||
| V. α-Ketoglutarate | 5. α-Ketoglutarate Dehydrogenase | Oxidative Decarboxylation | NAD+ CoA-SH |
NADH+H+ CO2 |
| VI. Succinyl-CoA | 6. Succinyl-CoA Synthetase | Hydrolysis | GDP Pi |
GTP CoA-SH |
| VII. Succinate | 7. Succinate Dehydrogenase | Oxidation | FAD | FADH2 |
| VIII. Fumarate | 8. Fumarase | Addition (H2O) | H2O | |
| IX. L-Malate | 9. Malate Dehydrogenase | Oxidation | NAD+ | NADH+H+ |
| X. Oxaloacetate | 10. Citrate Synthase | Condensation | ||
| XI. Acetyl-CoA |
The sum of all reactions in the citric acid cycle is :
- Acetyl-CoA + 3NAD+ + FAD + ADP + Pi ⇒
CoA-SH + 3NADH + H+ + FADH2 + ATP + 2CO2
Relation to other metabolic pathways
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Figure 2: Schematic drawing of metabolic pathways associated with the citric acid cycle.
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The citric acid cycle is the second step in carbohydrate catabolism (the breakdown of sugars). Glycolysis breaks glucose (a six-carbon-molecule) down into pyruvate (a three-carbon molecule). In eukaryotes, pyruvate moves into the mitochondria. It is converted into acetyl-CoA and enters the citric acid cycle.
In protein catabolism, proteins are broken down by protease enzymes into their constituent amino acids. These amino acids are brought into the cells and can be a source of energy by being funnelled into the citric acid cycle.
In fat catabolism, triglycerides are hydrolyzed to break them into fatty acids and glycerol. In the liver the glycerol can be converted into glucose via dihydroxyacetone phosphate and glyceraldehyde-3-phosphate by way of gluconeogenesis. In many tissues, especially heart, fatty acids are broken down through a process known as beta oxidation which results in acetyl-CoA which can be used in the citric acid cycle. Sometimes beta oxidation can yield propionyl CoA which can result in further glucose production by gluconeogenesis in liver.
The citric acid cycle is always followed by oxidative phosphorylation. This process extracts the energy from NADH and FADH2, recreating NAD+ and FAD, so that the cycle can continue. The citric acid cycle itself does not use oxygen, but oxidative phosphorylation does.
The total energy gained from the complete breakdown of one molecule of glucose by glycolysis, the citric acid cycle and oxidative phosphorylation equals about 38 ATP molecules.
