Fig. 3
From: Glutamate dehydrogenase hyperinsulinism: mechanisms, diagnosis, and treatment
Mechanism of GDH mediated hypoglycemia/hyperammonemia in GDH-HI. In the beta cells, oxidation of glucose and activation of GDH by leucine increase the ratio of ATP/ADP, which leads to the closure of ATP-dependent potassium channels, the depolarization of cell membrane, the influx of calcium ions, and insulin secretion. In the hepatocytes, glutamate can produce ammonia catalyzed by GDH. Glutamate also generates N-acetylglutamate, an allosteric activator of CPS, to regulate ammonia detoxification into urea. In the renal tubular cells, GDH catalyzes glutamate to produce α-ketoglutarate and ammonia. GDH, glutamate dehydrogenase; TCA cycle, tricarboxylic acid cycle; CPS, carbamoyl phosphate synthetase