Question

Explain the mechanism of action of the enzyme aconitase on citrate in TCA cycle.

Answer 1

Aconitase is an enzyme that catalyses the isomerization of citrate to isocitrate. Aconitase provides dehydration-hydration reaction. Two major amino acid residues mediate the reaction. Histidine-101 protonates the hydroxyl group on C3 of citrate leading to the release of water. Serine-642 interacts with the proton on C2, resulting in the formation of a double bond between C2 and C3 (cis-aconitate intermediate). Next, the intermediate mooecule is rotated 180°, while -OH group is added back to C2 and proton is added to C3 resulting in the formation of isocitrate.