Regulation of glutamate dehydrogenase in hypometabolic states
Glutamate dehydrogenase (GDH) is a key enzyme in nitrogen metabolism and has significant roles in amino acid catabolism and urea biosynthesis. The role of this enzyme in important metabolic processes suggests that it may be regulated in animals that survive in unforgiving environments. Such animals typically respond to harsh environmental conditions with strong overall metabolic rate suppression as well as species- and tissue specific metabolic alterations. To better understand the role of amino acid metabolism in hypometabolism, GDH was investigated in hibernating Richardson’s ground squirrels (Spermophilus richardsonii), anoxia-tolerant freshwater turtles (Trachemys scripta elegans), and estivating land snails (Otala lactea). Studies analyzed GDH substrate affinities, effects of metabolite activators and inhibitors, pH and/or temperature effects, and the actions of protein kinases and protein phosphatases in modifying enzyme properties. Liver GDH from ground squirrels was regulated by reversible protein phosphorylation in a manner that could activate the oxidation of glutamate to assist in energy production and contribute to gluconeogenesis during hibernation. Similarly, foot muscle GDH from land snails was regulated by reversible phosphorylation with the subsequent activation of the glutamate-oxidizing reaction to aid in energy production and urea biosynthesis in the estivating state. Conversely, under conditions of oxygen deprivation, the freshwater turtle utilizes reversible phosphorylation to inactivate both the glutamate-oxidizing and glutamate-synthesizing reactions of GDH. Thus, it appears that GDH and its effects on amino acid metabolism play an important role in animals during hypometabolism.