Glutamate dehydrogenase (GDH) catalyses the reversible oxidative deamination of glutamate to α-ketoglutarate. This mitochondrial enzyme is regulated by negative cooperativity and a wide array of allosteric effectors. Among them, most potent inhibitor GTP and most potent activator ADP. The importance of GDH regulation has been highlighted by the discovery of the hyperinsulinism-hyperammonaemia (HI/HA) syndrome. It is caused by dominant activating mutations that abrogate GTP inhibition, resulting in dangerously high serum levels of insulin and ammonium.