Glutamate dehydrogenase: Structure, regulation, and its role in insulin homeostasis

This chapter reviews the structure and allosteric regulation of glutamate dehydrogenase (GDH). For decades, it was known that mammalian GDH was regulated by a wide array of metabolites, but the reason for such regulation was not at all clear. The demonstration that hyperinsulinism/hyperammonemia (HHS) is caused by the loss of some of this regulation, for the first time, demonstrated that GDH regulation was essential for insulin homeostasis. Presented here are the atomic details for this complex network of allosteric regulation and how such information can lead to development of pharmaceutical agents that might not only be useful in treating HHS, but may also have utility as anticancer agents.