Cycle:

The cycle forms the middle part of a three-step process which oxidizes organic fuel molecules into CO₂ with the concomitant production of ATP.

Steps 1 - Oxidation of fuel molecules to acetyl CoA

A main source of energy is glucose that is converted through glycolysis into pyruvate.  Pyruvate  dehydrogenase  (a complex  of three  enzymes  and five coenzymes)  then oxidizes  the pyruvate  (using  NAD⁺ that  is reduced  to NADH) to create CO₂and acetyl CoA. Because the reaction includes both an oxidation and a loss of CO₂, the procedure is known as oxidative decarboxylation.

Step 2 - The citric acid cycle

The cycle holds out the oxidation of acetyl groups from acetyl CoA to CO₂ with the production of four pairs of electrons which stored initially in the reduced electron carriers FADH₂ and NADH.

The cycle has eight stages that are:

1.  Citrate (6C) is created from the irreversible condensation of acetyl CoA (2C) and oxaloacetate (4C) - catalyzed through citrate synthase.

2.  Citrate is transformed to isocitrate (6C) through an isomerization catalyzed by aconitase. This is really a two-step reaction during which cis-aconitate is creating as an intermediate. It is the cis-aconitate that provides the enzyme its name.

3.  Isocitrate is oxidized to α-ketoglutarate (5C) and CO₂ through isocitrate dehydrogenase. This mitochondrial enzyme needs NAD⁺ that is reduced to NADH.

4.  α-Ketoglutarate is oxidized to succinyl CoA (4C) and CO₂ through the α-ketoglutarate dehydrogenase complex. Such as pyruvate dehydrogenase, that is a difficult of three enzymes and uses NAD⁺ as a cofactor.

5.  Succinyl CoA is converted to succinate (4C) by succinyl CoA synthetase. The reaction uses the energy released through cleavage of the succinyl-CoA bond to synthesize either GTP (mainly in animals) or ATP (exclusively in plants) from P_i and, correspondingly GDP or ADP.

6.  Succinate is oxidized to fumarate (4C) through succinate dehydrogenase.  FAD is strongly bound to the enzyme and is decrease to produce FADH₂.

7.  Fumarate is converted to malate (4C) through fumarase; this is a hydration reaction needed the addition of a water molecule.

Figure:  The citric acid cycle (reactions 1-8 are described in the text).

8.  Malate is oxidized to oxaloacetate (4C) through malate dehydrogenase.  NAD⁺ is again needs through the enzyme as a co-factor to accept the free pair of electrons and produce NADH.

Step 3 - Oxidation of NADH and FADH₂

Produced through the citric acid cycle The NADH and FADH₂ produced through the citric acid cycle are re-oxidized and the energy released is used to synthesize ATP through oxidative phosphorylation.