Intertissue Differences for the Role of Glutamate Dehydrogenase in Metabolism

The enzyme glutamate dehydrogenase (GDH) plays an important role in integrating mitochondrial metabolism of amino acids and ammonia. Glutamate may function as a respiratory substrate in the oxidative deamination direction of GDH, which also yields α-ketoglutarate. In the reductive amination direction GDH produces glutamate, which can then be used for other cellular needs such as amino acid synthesis via transamination. The production or removal of ammonia by GDH is also an important consequence of flux through this enzyme. However, the abundance and role of GDH in cellular metabolism varies by tissue. Here we discuss the different roles the house-keeping form of GDH has in major organs of the body and how GDH may be important to regulating aspects of intermediary metabolism. The near-equilibrium poise of GDH in liver and controversy over cofactor specificity and regulation is discussed, as well as, the role of GDH in regulation of renal ammoniagenesis, and the possible importance of GDH activity in the release of nitrogen carriers by the small intestine.