isocitrate is shown in balck, NAD+ in green and enzyme atoms in blue. This is the first step - oxidation of the isocitrate. While a base from the enzyme pulls on the hydrogen of the -OH group the H- (hydride) on the carbon transfers to NAD+. The red arrows show the movement of pairs of electrons

The results of the oxidation step are shown. What "was" the alcohol has been oxidixed to a ketone. The H+ is now associates with what was the base. and NAD+ has been reduced to NADH. The bblack dashed arrow indicates diffusion of NADH out of the active site.

The metal ion begins to attract one pair of electrons out from the C=O, consequently a different pair must "fill-in" - These come from the bond between the carbon next door and the carboxyl group. which pulls in the pair from the negative charge on the oxygen atom.

The results of the previous step are shown in this transition state. note the essential "enol" transition state group and that CO2 has already formed.

The electron flow to the TS now reverses with the C-O- collapsing back to the ketone, one pair of electrons from the C=C picks up a H+ from the acid (this was the initial base in the oxidation step)

the reaction is complete, CO2 and α ketoglutarate have been formed.

Aerobic Glucose Metabolism

Isocitrate Dehydrogenase Information

Enzyme Name

Isocitrate Dehydrogenase

Reaction Catalyzed

two step reaction:
  1. Oxidation of the alcohol (to a ketone)
  2. aldol reaction to eliminate the "middle" carboxylic acid

Reaction Type

 Two Step Reaction
  1. Redox
  2. Aldol Reaction

Pathway Involvement

Citric Acid Cycle

Cofactors/Cosubstrates

 Requires NAD+ as a cosubstrate for the oxidation and a metal ion (frequently magnesium) to aid the aldol reaction.