Question

The ligands bound to the mammalian GDH can tell us if and how this enzyme is regulated. How is the bovine GDH regulated and which ligands are involved in each type of regulation?

Answer 1

Bovine Glutamate Dehydrogenase is a homohexameric, mitochondrial enzyme which reversly catalyse the oxidative deamination of L-glutamate to 2- oxoglutararate with NADP(H).

Bovine GDH regulation :

The activity of bovine glutamate dehydrogenase (GDH) is affected by several factors like substrate concentrations and pH.

At pH 6.5 and below - oxidative deamination and reductive amination reactions are inhibited by ADP(Adenosine DiPhosphate) .

At pH 7.0 and above - activatory and inhibitory effects can be observed depending on substrate concentrations.

The activatory effects of ADP result from destabilisation of abortive complexes by ADP binding to its regulatory site.

In vivo concentrations of these various substrates involved and intramitochondrial pH and adenine nucleotide suggest that in vivo the reductive amination reaction is favoured.

Thus, GDH is involved in regulation of urea cycle by responding to changes in mitochondrial ammonia levels.

Ligands involved in GDH regulation :

ADP ( Adenosine Diphosphate ) and leucine are the activators .

GTP( Guanosine-5'triphosphate),ATP( Adenosine Triphosphate), palmitoyl coa are the inhibitors.