Citrate cycle

The citrate cycle, also known as the tricarboxylic acid or citric acid cycle, is the "turntable" of the metabolic system. Its most important function is the production of NADH for the respiratory chain. The hydrogen bound in NADH is oxidized to water in the mitochondrial membrane with molecular oxygen. The energy released in the process is used for ATP synthesis. This process, also known as oxidative phosphorylation, is the most efficient ATP-producing process.

The citrate cycle is a cycle at the centre of the metabolism of all oxygen-consuming living beings that is connected to the respiratory chain. It occurs in the mitochondria of eukaryotes and in the cytoplasm of prokaryotes. The citrate cycle is a central part of cellular respiration and is the third of four steps in carbohydrate catabolism (the breakdown of energy-rich, carbon-containing compounds). It takes place after glycolysis and oxidative decarboxylation and immediately before the respiratory chain.

The most important function of the citrate cycle is to oxidise acetyl-CoA, which originates from oxidative decarboxylation, β oxidation of fatty acids or amino acid degradation, to CO2 in eight reactions. First, acetyl-CoA transfers its acetyl group (C2) to the C4-compound oxaloacetate, resulting in the C6-compound citrate. Successive oxidative decarboxylations release two CO2, so that oxaloacetate is ultimately formed again, which can again take up an acetyl group. The released energy is fixed in the form of the reduction equivalents NADH and FADH2. These release the absorbed electrons to the respiratory chain, where they are transferred to oxygen. In addition, a GTP or an ATP is formed in the citrate cycle. The enzymes of the citrate cycle, like those of the respiratory chain, are located in the mitochondrium.

The complete oxidation of one molecule of glucose produces a total of about 38 molecules of ATP, two in glycolysis, two in the citrate cycle and 34 in oxidative phosphorylation.

The energy balance for the oxidation of one acetyl group to CO2 is: 3 NADH, 1 FADH2 and 1 GTP or ATP

• Acetyl-CoA reacts with oxaloacetate to form citrate. The released coenzyme A can bind another pyruvate.
• The isomer isocitrate is formed by splitting off and simultaneous absorption of water.
• From the substrate is split off and electrons and protons are transferred. Alpha-Ketogluterat is formed.
• A further molecule is split off. The remaining substrate is oxidized and coupled to the coenzyme A by releasing electrons and protons. Formation of succinyl-CoA.
• The coenzyme A is released again. Via intermediate reactions 2 molecules of ATP are formed, the only energy gain in the citrate cycle. Succinate is formed in the process.
• During the oxidation of the substrate the hydrogen atoms are transferred to FAD. FAD is similar to this. It also acts as electron acceptor (FAD = flavinadenine dinucleotide). Formation of fumarate.
• In the following reaction, bonds in the substrate are rearranged with the addition of water. Formation of malate.
• By electron and proton transfer oxalacetate is formed again. Regeneration of this compound enables the cyclic course of the reaction. Formation of oxaloacetate.

The following enzymes are involved in the citrate cycle:

• Citrate synthase
• Aconitase
• Isocitrate dehydrogenase
• Ketoglutarate dehydrogenase
• Succinyl-CoA synthase
• Succinate dehydrogenase
• Fumarase
• Malate dehydrogenase