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The effect of orthovanadate, vanadyl sulphate and vanadyl acetylacetonate on glutamate dehydrogenase activity was studied in liver mitochondria and isolated hepatocytes of rabbit. In permeabilized mitochondria with free access of substrates and drugs to glutamate dehydrogenase, orthovanadate and vanadyl sulphate at 200 microM concentrations decreased both glutamate synthesis and glutamate deamination by 80 and 50%, respectively, while vanadyl acetylacetonate was less potent. In view of kinetic data obtained at various ammonium concentrations, orthovanadate appeared to be a competitive inhibitor (Ki = 40 +/- 3 microM), while vanadyl sulphate was a non-competitive one (Ki = 147 +/- 10 microM). In contrast to orthovanadate, vanadyl sulphate augmented the inhibitory action of increased above 0.5 mM 2-oxoglutarate concentrations. All these effects on the enzyme activity were partially reversed in the presence of L-leucine and ADP, which are allosteric activators of glutamate dehydrogenase. Moreover, all compounds studied suppressed both glutamate formation and glutamate deamination in isolated hepatocytes incubated under various metabolic conditions, as concluded from decreased rates of glutamate and urea synthesis, respectively. In view of these observations it seems likely that vanadium-containing compounds may be potent inhibitors of glutamate metabolism in liver.

Glycogen phosphorylase activity in both liver and kidney medulla of rabbit was stimulated in the presence of caffeine by various aminoglycoside antibiotics in the following rank order: gentamicin greater than neomycin greater than amikacin = kanamycin greater than or equal tobramycin, while streptomycin did not affect the enzyme activity. In contrast, in the presence of AMP, the stimulatory action of antibiotics was not observed. Since in the gentamicin-treated rabbits stimulation of glycogen phosphorylase activity by about 30% in both liver and kidney medulla was accompanied by a decrease of liver glycogen content by about 60% it is likely that a decline in liver glycogen level following antibiotic treatment is due to an increased glycogen phosphorylase activity.

1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits.