Best answer class 11|| TCA cycle:
Introduction to citric acid cycle:
In the year of 1937,the scientist, Hans Adolf Krebs proposed the citric acid cycle.He proposed this cycle based on the studies of oxygen consumption in pigeon breast muscle.
The TCA cycle is the central metabolic hub of the cell.
The primary metabolic fate of acetyl CoA produced,in the various energy-generating catabolic pathways of most cells is it's complete oxidation in a cyclic series of reactions, termed the TCA(Tri Carboxylic Acid) cycle.
The citric acid cycle is also known as tricarboxylic acid-TCA cycle or Krebs cycle after the discoverer sir Hans Adolf Krebs,who postulated the key features of this pathway in the year of 1937.
The TCA cycle is mostly involved in the energy supply to the body.The citric acid cycle is also involves in the utilization of about two thirds of total oxygen consumed by the body.
The critic acid cycle is also an important source of precursors not only for the storage forms of fuels but also for the building blocks of many other molecules such amino acids, nucleotide bases, cholesterol, porphyrin etc.
In this cycle acetyl CoA is oxidized to Co2 and H2o.
Since, at the outset of the cycle tricarboxylic acids participate, that's why the name TCA cycle is given.
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Citric acid cycle with aconitate ,Image by-Narayanese,WikiUserPedia ,YassineMrabet ,TotoBaggins ,Source , License-CC BY-SA 3.0 |
Reactions of citric acid cycle:
The events which takes place during TCA ,are described below,
1.Formation of citrate:
The first reaction ,which occurs during TCA cycle ,is the condensation of acetyl CoA with oxaloacetate.
The enzyme ,which is involved in this step is citrate synthase.
In this reaction the methyl carbon of the acetyl group is joined to the carbonyl group of oxaloacetate.
2. Formation of Isocitrate via cis-Aconitate:
After the formation of citrate ,in this step, the enzyme aconitase catalyzes the reversible transformation of citrate to isocitrate , through the intermediary formation of the tri-carboxylic acid cis-aconitate ,which normally does not dissociate from the active site.
Aconitase can promote the reversible addition of H2o to the double bond of enzyme bound cis-aconitate in two different ways,one leading to the formation of citrate and the other to iso-citrate.
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3.Oxidation of Iso-citrate to alpha keto-glutarate and carbon-di-oxide:
In this step the enzyme iso-citrate dehydrogenase (ICD) catalyses the oxidative decarboxylation of iso-citrate to oxalosuccinate and then to alpha-ketoglutarate .
The formation of NADH and the liberation of Co2 occur at this stage.
4. Conversion of alpha-ketoglutarate to succinylcholine CoA:
In this step oxidative decarboxylation of alpha ketoglutarate leads to the formation of succinyl CoA and Co2 .
The enzyme, which catalyses this reaction is alpha ketoglutarate dehydrogenase complex.NAD+ serves as the electron acceptor and CoA as the carrier of the succinyl group.
5. Conversion of succinyl-CoA to succinate:
In this step of TCA cycle Succinyl CoA is converted to succinate by succinate thiokinase. This reaction is coupled with the phosphorylation of GDP to GTP .
This is an example of substrate level phosphorylation.
GTP is converted to ATP by the enzyme nucleoside diphosphate kinase.
6.Oxidation of succinate to fumarate:
In this step of TCA cycle ,succinate ,which is formed from Succinyl CoA is oxidized to fumarate. Succinate dehydrogenase (flavoprotein) is the enzyme that catalyses this reaction.This reaction results in the production of FADH2.
7. Formation of malate:
The reversible hydration of fumarate to L-malate is catalyzed by fumarase. The transition state in this reaction is a carbanion.The enzyme fumarase is highly stereospecific .
This enzyme is involves in the hydration of the trans double bind of fumarate but not the cis double bond of malate. In the reverse direction fumarse is equally stereospecific:D-malate is not a substrate.
8. Conversion of malate to oxaloacetate:
In this step ,which is also the last step of the TCA cycle , L-malate dehydrogenase catalyzes the oxidation of L-malate and leads to the formation of oxaloacetate , coupled to the reduction of NAD+ to NADH.
The oxaloacetate is regenerated which can combine with another molecule of acetyl CoA ,and continue the cycle .
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