Sandbox Reserved 761: Difference between revisions

==Regulation of Glutamate Dehydrogenase==

GTP is a potent inhibitor for the reaction and binds at the base of the antenna, wedged in between the NAD binding domain and the pivot helix. This binding site is only available for GTP binding when the catalytic cleft is closed. Therefore, after GTP binds to the 'closed' conformation it is more difficult for the 'mouth' to open and release either NAD+ and NADP+ as coenzyme (1).  

In the reductive amination reaction, ADP is a potent activator at low pH and low substrate concentration. ADP acts by destabilizing the abortive complexes, and abrogating the negative cooperativity. In the absence of substrates, and with bound ADP, the catalytic cleft is in the open conformation, and the GDH hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals. However, at pH 6.0 and high concentrations of α-ketoglutarate and NADH, the reaction is inhibited. This substrate inhibition is alleviated by ADP. Therefore, while GTP and glutamate bind synergistically with NADH to inhibit GDH, ADP activates the reaction by decreasing the affinity of the active site. However, under conditions where the enzyme is not saturated (e.g. low substrate concentrations), this loss in binding affinity causes inhibition.

NADH, is another major allosteric inhibitor of GDH

This oxidized coenzyme binding causes activation

Different concentration levels of ATP have different effects on GDH activity:

-Low [ATP] causes inhibition due to mediated through the GTP binding site.