Citric acid cycle

In biochemistry, the Citric Acid Cycle, also called Krebs cycle, Citrate Cycle, Tricarboxylic Acid Cycle or TCA, is a series of chemical reactions of central importance in all living cells 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.

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. Fumerase	Addition (H2O)	H2O
IX. L-Malate	9. Malate Dehydrogenase	Oxidation	NAD+	NADH+H+
X. Oxaloacetate	10. Citrate Synthetase	Condensation
XI. Acetyl-CoA

The sum of all reactions in the citric acid cycle is :

Acetyl-CoA + 3NAD⁺ + FAD⁺ + ADP + P_i ⇒
CoA-SH + 3NADH + H⁺ + FADH₂ + ATP + 2CO₂

Two carbons are oxidized to CO₂, and the energy from these reactions are stored in ATP (ATP is the "universal energy currency" of the cell), NADH and FADH₂. NADH and FADH₂ are coenzymes[?] (Coenzymes are molecules that enable or enhance enzymes.) that store energy and can release it when needed.

Relation to other metabolic pathways

Figure 2 : Schematic drawing of metabolic pathways associated with the citric acid cycle. Protein catabolism. Fat catabolism. Carbohydrates. Amino Acids. Acetyl-CoA. Pyruvate. Citric Acid Cycle.

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 outside the cells by protease enzymes. The amino acids are brought inside the cells and funnel into glycolysis or the citric acid cycle.

In fat catabolism, triglycerides are hydrolyzed to break them into fatty acids and glycerol. The glycerol is then converted into glyceraldehyde-3-phosphate, and enters glycolysis and eventually the ctric acid cycle. Fatty acids are broken down through a process known as beta oxidation[?] which results in acetyl-CoA to be used in the citric acid cycle.

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 38 ATP.