INHIBITORY EFFECT OF VANADIUM COMPOUNDS ON GLUTAMATE-DEHYDROGENASE ACTIVITY IN MITOCHONDRIA AND HEPATOCYTES ISOLATED FROM RABBIT LIVER

The effect of orthovanadate, vanadyl sulphate and vanadyl acetylaceton ate on glutamate dehydrogenase activity was studied in liver mitochond ria and isolated hepatocytes of rabbit. In permeabilized mitochondria with free access of substrates and drugs to glutamate dehydrogenase, o rthovanadate and vanadyl sulphate at 200 mu M concentrations decreased both glutamate synthesis and glutamate deamination by SO and 50 %, re spectively, while vanadyl acetylacetonate was less potent. In view of kinetic data obtained at various ammonium concentrations, orthovanadat e appeared to be a competitive inhibitor (K-i=4O+/-3 mu M), while vana dyl sulphate was a non-competitive one (K-i=147+/-10 mu M). In contras t to orthovanadate, vanadyl sulphate augmented the inhibitory action o f increased above 0.5 mM 2-osoglutarate concentrations. All these effe cts on the enzyme activity were partially reversed in the presence of L-leucine and ADP which are allosteric activators of glutamate dehydro genase. Moreover, all compounds studied suppressed both glutamate form ation and glutamate deamination in isolated hepatocytes incubated unde r various metabolic conditions, as concluded from decreased rates of g lutamate and urea synthesis, respectively. In view of these observatio ns it seems likely that vanadium-containing compounds may be potent in hibitors of glutamate metabolism in liver.