Answer to Question #101582 in Chemistry for NIBEDITA RURA

Question

Explain the mechanism of action of the enzyme aconitase on citrate in TCA cycle.
Compare the energetics of metabolic oxidation of glucose and a fatty acid.

Answer 1

Aconitase is an enzyme that converts citrate into isocitrate. Aconitase contains the 4Fe-4S cofactor that is held by three sulphur atoms of cysteines. During the activation, a fourth iron atom is included in the cluster together with a water molecule. Substrate-free aconitase contains a [4Fe-4S]2+ cluster, while one of the iron ions is attached to hydroxyl bound. When citrate interacts with the enzyme, the bound hydroxyl is protonated. Next, a hydrogen bond formed by His-101 and isocitrate hydroxyl is donated resulting in the formation of water. At the same time, the proton is donated by His-167, which is also bonded to a water molecule in the [4Fe-4S] cluster. The conformational change caused by citrate binding results in the reorientation of the cluster. Ser-642 removes a proton from citrate resulting in the formation of the intermediate molecule - cis-aconitate. Finally, the rehydration of the double bond leads to the formation of isocitrate.

Oxidation of glucose is performed glycolytic enzymes and TCA cycle enzymes. During glycolysis, glucose breakdown is associated with the formation of pyruvate that is further transformed into acetyl-CoA. Fatty acids are metabolized during beta-oxidation reactions resulting in the formation of acetyl-CoA. As a result, glycolysis and beta-oxidation result in the formation of acetyl-CoA that directly enters the TCA cycle. As a result, metabolic oxidation of one glucose to two acetyl-CoA molecules results in the formation of 8 ATP, while beta-oxidation of palmitate to eight acetyl-CoA is associated with the formation of 26 ATP.