Isocitrate dehydrogenase

From Proteopedia

Mechanism

The mechanism described is for porcine isocitrate dehydrogenase because is is better understood than the human mechanism. The alcohol group off the alpha-carbon is deprotonated by the Tyr residue. The electrons push to the oxygen atom to form a double bond (keytone). The remaining alpha carbon hydrogen is removed using NAD+/NADP+ as an electron accepting cofactor. A carboxyl group pushes electrons down so an oxygen steals a nearby proton off a Lysine amino acid. The Tyr deprotanates the carboxylic acid resulting in electron pushing that ejects a CO2. The two negatively charged oxygen's on the other side of the molecule are stabilized by the Mn2+. The double bond that was formed between the alpha and beta carbon removes a proton from the Tyr residue and the oxygen returns the a keytone and the alpha-ketoglutarate is formed. This is illustrated in the figure below.

The mechanism of porcine isocitrate dehydrogenase