Posts Tagged ‘TCA cycle’
Citric acid cycle (also called Krebs cycle or TCA cycle) is the second stage of cellular respiration in which Acetyl Co-A is metabolized to carbon dioxide and water, and reduces co-enzymes that are re-oxidized through the electron transport chain, linked to the generation of ATP. It occurs totally in the mitochondria of a cell. The enzymes of citric acid cycle are located in the mitochondrial matrix either free form or attached to the inner side of the inner mitochondrial membrane. In this stage, requires oxygen for the final electron acceptor and does not function under anaerobic conditions.
The Citric acid cycle is the final pathway for oxidation of carbohydrates, proteins, and lipids. The major entry into Citric acid cycle is through Acetyl Co-A. Acetyl Co-A is the substrate of this cycle that arises from the breakdown of glucose, most amino acids, and fatty acids. A small number of amino acids are converted into intermediates of citric acid cycle by the process of deamination.
Reactions of citric acid cycle:
(1) Formation of citrate from Acetyl CoA and oxaloacetate:
The cycle starts with the reaction between the acetyl group of Acetyl CoA and oxaloacetate (four-carbon dicarboxylic acid) to form citrate (six-carbon tri carboxylic acid), the reaction is catalyzed by citrate synthase.
(2) Isomerization of citrate:
Citrate is isomerized to isocitrate by enzyme aconitase.
(3) Dehydrogenation and decarboxylation of isocitrate:
Isocitrate undergoes dehydrogenation reaction catalyzed by enzyme isocitrate dehydrogenase, formimg initially, oxalosuccinate and undergoes decarboxylation to form alpha-ketoglutarate, the first NADH of the cycle and the first release of CO2.
(4) Oxidative decarboxylation of alpha-ketoglutarate:
Alpha-ketoglutarate undergoes oxidative decarboxylation catalyzed by enzyme alpha-ketoglutarate dehydrogenase complex to form succinyl CoA. This reaction produces the second NADH and releases the second CO2.
(5) Cleavage of succinyl CoA:
Succinyl CoA is converted into succinate by succinate thiokinase. This reaction produces GTP. GTP and ATP are energetically interconvertible.
(6) Oxidation of succinate:
Succinate dehydrogenase enzyme oxidized the succinate into fumarate and produced the reduced coenzyme FADH2.
(7) Hydration of fumarate:
Fumarate is hydrated into malate catalyzed by fumerase.
(8) Oxidation of malate:
Malate is oxidized into oxaloacetate by the enzyme malate dehydrogenase. This reaction releases the third and final NADH molecules of citric acid cycle.
Energy production in citric acid cycle:
Two carbon atoms enter into the citric acid cycle as Acetyl Co-A and leave as carbon dioxide (CO2). Four pairs of electrons are removed from the substrate; three pairs leave in the form of NADH, and one pair leaves as FADH2. These energy rich molecules, NADH and FADH2 are oxidized in the third stage of cellular respiration via the electron transport chain for ATP generation. Calculation of total ATP generation in citric acid cycle:
|Energy molecule||Number of ATP production|
|3 NADH||3×3= 9|
Oxidation of one molecule of Acetyl Co-A via Citric acid cycle gives 12 molecules of ATP.