What is TCA cycle? Describe its different steps.
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Acetyl CoA then enters a cyclic pathway, tricarboxylic acid cycle, more commonly called as Krebs cycle. Krebs cycle was named after the scientist Hans Krebs who first elucidated in flight muscles of pigeons. In these reactions hydrogen atoms are removed from the acetyl CoA and transferred to the coenzymes for further processing in the electron transport system.
Krebs Cycle proceeds in following steps :
- Acetyl group combines with oxaloacetic acid (OAA) and water to yield citric acid and this reaction is catalyzed by citrate synthetase and a molecule of CoA is released.
- Citric acid changes to isocitrate by the action of aconitase.
- Isocitrate dehydrogenase oxidizes isocitrate to oxalosuccinic acid by removing hydrogen and converting to
- Next step is of decarboxylation where CO2 is released from six carbon oxalosuccinic acid and results in the formation of -ketoglutaric acid which is five carbon compound from oxalosuccinic acid.
- -ketoglutaric dehydrogenase complex acts on -ketoglutaric acid and converts it into a four carbon compound succinyl CoA. During this step is released and NAD is reduced to NADH + .
- In the next step succinate thiokinase catalyzes the conversion of succinyl CoA to succinic acid during this step CoA is released and one molecule of GTP is from GDP. (This is a substrate level phosphorylation. In a coupled reaction GTP is converted to GDP with the simultaneous synthesis of ATP from ADP).
- Fumaric acid is formed in the next step from succinic acid this reaction is catalyzed by succinate dehydrogenase. During this reaction FAD molecule is reduced to .
- Malic acid is formed by the action of fumarase on fumaric acid this step involves addition of water molecule.
- Regeneration of oxaloacetic acid is the last step that occurs in this reaction which is catalyzed by malic dehydrogenase which reduces to by removing hydrogen from malic acid.
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↗ The citric acid cycle was proposed by Hans Adolf Krebs in 1937 based on the studies of oxygen consumptions in pigeon breast muscle.
↗ TCA cycle operates in the mitochondrial matrix.
- Acetyl CoA combines with oxaloacetate in the presence of condensing enzyme citrate synthase to form a citric acid. It is the first product of Kreb's cycle. CoA is liberated.
- Citrate undergies reorganisation in the presence of aconitase forming cis-acotinate and water.
- Cis-acotinate is converted into isocitrate with the addition of water in the presence of enzyme acotinase.
- Isocitrate is dehydrogenated to oxalosuccinate in the presence of enzyme isocitrate dehydrogenase and Mn(+2). NADH_2 is produces.
- Oxalosuccinate is decarboxylated to form α-ketoglutarate through the enzyme decarboxylase. This step releases one CO_2.
- α-ketoglutarate is both dehydrogenated and decarboxylated by an enzyme complex α-ketoglutarate dehydrogenase.
- The product combines with CoA to form succinyl CoA. To continue the cycle, succinyl CoA is converted to succinic acid by the enzyme succinyl thiokinase. This reaction requires GDP. ATP may be formed from GTP. A nucleoside diphosphokinase catalyses phosphate transfer from GTP to ADP.
- Succinic acid is metabolized to fumaric acid by dehydration. It is the only reaction in the citric acid cycle which involves the direct transfer of hydrogen from the substrate to FAD without the participation of NAD.
- A molecule of water gets added to fumarate to form malate. The enzyme is called fumarase.
- Malate is dehydrogenated or oxidised of activated to repeat the cycle, as two molecules of acetyl-CoA are formed from one molecule of glucose. A total of 24ATP are produced from one acetyl CoA.
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