Two aspartate amino acid residues (below left) are interacting with two adjacent water molecules (w6 and w8) in the Mn²⁺ isocitrate porcine IDH complex to deprotonate the alcohol off the alpha-carbon atom.
The oxidation of the alpha-C also takes place in this picture where NAD⁺ accepts a hydride resulting in oxalosuccinate.
Along with the sp³ to sp² stereochemical change around the alpha-C, there is a ketone group that is formed form the alcohol group.
The formation of this ketone double bond allows for resonance to take place as electrons coming down from the leaving carboxylate group move towards the ketone.

The decarboxylation of oxalosuccinate (below center) is a key step in the formation of alpha-ketoglutarate.
In this reaction, the lone pair on the adjacent Tyrosine hydroxyl abstracts the proton off the carboxyl group.
This carboxyl group is also referred to as the beta subunit in the isocitrate molecule.
The deprotonation of the carboxyl group causes the lone pair of electrons to move down making carbon dioxide and separating from oxalosuccinate.
The electrons continue to move towards the alpha carbon pushing the double bond electrons (making the ketone) up to abstract a proton off an adjacent lysine residue.
An alpha-beta unsaturated double bond results between carbon 2 and three.
As you can see in the picture, the green ion represents either Mg²⁺ or Mn²⁺, which is a cofactor necessary for this reaction to occur.
The metal-ion forms a little complex through ionic interactions with the oxygen atoms on the fourth and fifth carbons (also known as the gamma subunit of isocitrate).

After the carbon dioxide is split from the oxalosuccinate in the decarboxylation step (below right), the enol will tautomerize to the keto from.
The formation of the ketone double bond is started by the deprotonation of that oxygen off the alpha carbon (C#2) by the same lysine that protonated the oxygen in the first place.
The lone pair of electrons moves down kicking off the lone pairs that were making the double bond.
This lone pair of electrons abstracts a proton off the Tyrosine that deprotonated the carboxyl group in the decarboxylation step.
The reason that we can say that the Lys and Tyr residues will be the same from the previous step is because they are helping in holding the isocitrate molecule in the active site of the enzyme.
These two residues will be able to form hydrogen bonds back and forth as long as they are close enough to the substrate.

The isocitrate dehydrogenase enzyme as stated above produces alpha-ketoglutarate, carbon dioxide, and NADH + H⁺/NADPH + H⁺. There are three changes that occurred throughout the reaction.
The oxidation of Carbon 2, the decarboxylation (loss of carbon dioxide) off Carbon 3, and the formation of a ketone group with a stereochemical change from sp³ to sp².
Two aspartate amino acid residues (below left) are interacting with two adjacent water molecules (w6 and w8) in the Mn²⁺ isocitrate porcine IDH complex to deprotonate the alcohol off the alpha-carbon atom. The oxidation of the alpha-C also takes place in this picture where NAD⁺ accepts a hydride resulting in oxalosuccinate. Along with the sp³ to sp² stereochemical change around the alpha-C, there is a ketone group that is formed form the alcohol group. The formation of this ketone double bond allows for resonance to take place as electrons coming down from the leaving carboxylate group move towards the ketone.
The decarboxylation of oxalosuccinate (below center) is a key step in the formation of alpha-ketoglutarate. In this reaction, the lone pair on the adjacent Tyrosine hydroxyl abstracts the proton off the carboxyl group. This carboxyl group is also referred to as the beta subunit in the isocitrate molecule. The deprotonation of the carboxyl group causes the lone pair of electrons to move down making carbon dioxide and separating from oxalosuccinate. The electrons continue to move towards the alpha carbon pushing the double bond electrons (making the ketone) up to abstract a proton off an adjacent lysine residue. An alpha-beta unsaturated double bond results between carbon 2 and three. As you can see in the picture, the green ion represents either Mg²⁺ or Mn²⁺, which is a cofactor necessary for this reaction to occur. The metal-ion forms a little complex through ionic interactions with the oxygen atoms on the fourth and fifth carbons (also known as the gamma subunit of isocitrate).
After the carbon dioxide is split from the oxalosuccinate in the decarboxylation step (below right), the enol will tautomerize to the keto from. The formation of the ketone double bond is started by the deprotonation of that oxygen off the alpha carbon (C#2) by the same lysine that protonated the oxygen in the first place. The lone pair of electrons moves down kicking off the lone pairs that were making the double bond. This lone pair of electrons abstracts a proton off the Tyrosine that deprotonated the carboxyl group in the decarboxylation step. The reason that we can say that the Lys and Tyr residues will be the same from the previous step is because they are helping in holding the isocitrate molecule in the active site of the enzyme. These two residues will be able to form hydrogen bonds back and forth as long as they are close enough to the substrate.
The isocitrate dehydrogenase enzyme as stated above produces alpha-ketoglutarate, carbon dioxide, and NADH + H⁺/NADPH + H⁺. There are three changes that occurred throughout the reaction. The oxidation of Carbon 2, the decarboxylation (loss of carbon dioxide) off Carbon 3, and the formation of a ketone group with a stereochemical change from sp³ to sp².
Isocitrate dehydrogenase