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==Glutamate Dehydrogenase Mechanism== | ==Glutamate Dehydrogenase Mechanism== | ||
[[Image:GDH.jpg|frame|left|250px|Figure 4. Mechanism of Glutamate Dehydrogenase]] | |||
The first step in the mechanism for catalytic activity of GDH is the deprotonation of the α-amino group of glutamate via Asp 165, which acts as a general base. Next, a hydride transfer to NAD+ occurs, forming a Schiff base intermediate <ref>PMID:8263917</ref>. During the first step a large movement between C-domain and N-domain occurs, which closes the cleft and brings C4 of the nicotinamide ring and the α-carbon of the substrate into the correct position for a hydride transfer <ref>PMID:9405044</ref>. The second step in the mechanism of GDH involves the attack of a water molecule on the Schiff base intermediate. This step is enhanced by Lys 125. The direction of the attack is very specific, so that the stereochemistry of the developing carbinolamine will be the L isomer and not the D isomer. During the generation of the carbinolamine intermediate and its conversion to alpha ketoglutarate, residue Asp 165 is very crucial for the transfer of the protons to and from the substrate. The final step that GDH catalyzes involves the loss of a single proton from each Lys 125 and Asp 165, which is transferred from water to GDH <ref>PMID:8263917</ref>. | The first step in the mechanism for catalytic activity of GDH is the deprotonation of the α-amino group of glutamate via Asp 165, which acts as a general base. Next, a hydride transfer to NAD+ occurs, forming a Schiff base intermediate <ref>PMID:8263917</ref>. During the first step a large movement between C-domain and N-domain occurs, which closes the cleft and brings C4 of the nicotinamide ring and the α-carbon of the substrate into the correct position for a hydride transfer <ref>PMID:9405044</ref>. The second step in the mechanism of GDH involves the attack of a water molecule on the Schiff base intermediate. This step is enhanced by Lys 125. The direction of the attack is very specific, so that the stereochemistry of the developing carbinolamine will be the L isomer and not the D isomer. During the generation of the carbinolamine intermediate and its conversion to alpha ketoglutarate, residue Asp 165 is very crucial for the transfer of the protons to and from the substrate. The final step that GDH catalyzes involves the loss of a single proton from each Lys 125 and Asp 165, which is transferred from water to GDH <ref>PMID:8263917</ref>. | ||
==Regulation of Glutamate Dehydrogenase== | ==Regulation of Glutamate Dehydrogenase== | ||