Citrate cycle

The citrate cycle (tricarboxylic acid cycle, TCA cycle) is an oxidation cycle in which fuel molecules are oxidised (burned) to form carbon dioxide. The fuel molecules originate from fats (acetyl-CoA), sugars (acetyl-CoA, see also glycolysis) and amino acids (acetyl-CoA, alpha-ketoglutarate, succinate and ketosuccinate). By far, most fuel molecules are provided as acetyl-CoA.

The top part from pyruvate to acetyl-coenzyme A does not belong to the citrate cycle, but it is stated as a continuation on the glycolysis.


The reactions in which NAD + is converted in NADH and GDP to GTP and FAD to FADH2 means that energy has been released and that this energy is stored in these formed compounds. This energy can be used for a lot of purposes.

Citrate is converted into iso-citrate by firstly a dehydratation (cleavage of water) so that cis-aconitate is formed. Then cis-aconitate is hydrated (water added) and iso-citrate is formed. This reaction is catalysed by aconitase.
This transformation of a tertiary alcohol in a secondary alcohol is necessary for the next reaction in which the hydroxyl(-OH)- group must be oxidised to form a carbonyl(=O)group.




Firstly iso-citrate is converted into oxalosuccinate. This oxalosuccinate is now easy to decarboxylate (COO cleavage) to form alpha-ketoglutarate. The here released energy is stored in the molecule NADH. This reaction is catalysed by isocitrate dehydrogenase.




In this step alpha-ketoglutarate is decarboxylised to form succinyl CoA by the coenzyme-A which couples to alpha-ketoglutarate instead of the COO- group. The energy released hereby is stored in NADH.
This reaction is catalysed by alpha-ketoglutarate hydrogenase-complex.




The succinate-CoA is transformed in succinate by the cleavage of coenzyme-A and to replace it with an oxygen atom. The energy released hereby is stored in GTP.
This reaction is catalysed by succinate-CoA-synthetase.




The succinate is dehydrogenised (also an oxidation reaction) to fumarate. The energy that is released is stored in the FADH2 molecule. This reaction is catalysed by succinate dehydrogenase.




The addition of water to fumarate, results in the formation of malate. This reaction is catalysed by fumarase.




The hydroxyl group (-OH) of malate is oxidised to a carbonyl group (=O). The newly formed compound is called oxaloacetate. In this reaction, energy is released and is stored in the molecule NADH.
This reaction is catalysed by malate dehydrogenase.




The carbonyl group (=O) in oxaloacetate is coupled to acetyl-coenzyme A (a nucleophilic addition), from this citric acid is formed. This reaction is catalysed by citrate synthase.
From here the cascade of reaction starts again and the citric acid cycle is round.

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References

[1]. Stryer, Lubert;- Biochemistry - fourth edition; New York: W. H. Freeman and Company (1995). ISBN 0-7167-2009-4
[2]. Wolters-Noordhoff; - Binas - third busily; Groningen: Wolters-Noordhoff inc (1992). ISBN 90 , 0189372 , 4