Regulation of liver glutamate dehydrogenase by reversible phosphorylation in a hibernating mammal.
Glutamate dehydrogenase (GDH) is a key enzyme that links amino acid and carbohydrate metabolism in cells. Regulation is likely most important when organisms are confronted with extreme stresses such as the low environmental temperatures and lack of food associated with winter. Many small mammals, such as Richardson's ground squirrels, Spermophilus richardsonii, cope with these conditions by hibernating. Animals enter long periods of profound torpor where metabolic rate is greatly suppressed, body temperature drops to near-ambient and all metabolic needs must be met from fixed internal body stores of fuels. To investigate how GDH is regulated under these conditions, kinetic properties of GDH were analyzed in liver from euthermic and torpid squirrels, revealing significant differences in V(max), K(m) glutamate, K(a) ADP and inhibition by urea between the two forms of GDH. These data suggested an activation of the glutamate-oxidizing activity of GDH in the hypometabolic state. Subsequent experiments suggested that the molecular basis of the kinetic differences was a change in the protein phosphorylation state of GDH between euthermia and torpor. Specifically, liver GDH appears to be dephosphorylated and activated when animals transition into torpor and this may serve to promote amino acid oxidation to contribute to energy production and gluconeogenesis. This is the first study to show that mammalian liver GDH can be regulated by reversible phosphorylation, providing an important new regulatory mechanism for GDH control.
Bell
Ryan A V
RA
Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6.
Storey
Kenneth B
KB
D000818:Animals; D004795:Enzyme Stability; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006605:Hibernation; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D010766:Phosphorylation; D012589:Sciuridae / Q000378:metabolism / Q000502:physiology
D009249:NADP; D005969:Glutamate Dehydrogenase