Hepatic l-glutamate dehydrogenase: Changes in activity and kinetic properties in response to small molecules

A marked increase in the activity of l-glutamate dehydrogenase was observed when liver slices were incubated in the presence of malate, lactate, glutamate, or α-ketoglutarate. This increased activity was insensitive to both actinomycin D and puromycin. The GDH of perfused rat liver and of liver homogenates was also activated when Earle's balanced salt solution containing malate was utilized as perfusate or diluent. The endogenous and activated forms of the enzyme differed in several kinetic properties (Km, analogue reactivity, and citrate effects), but not their electrophoretic properties. The increased GDH activity and concomitant complete loss of AlaDH activity suggest that malate is effecting a conformational change in the enzyme subunits.