RESULTS

E $ ects on Oxidation and Phosphorylation--The effects of various concentrations of phenethylbiguanide on oxidation and coupled phosphorylations of various substrates by rat liver mitochondria are presented in Table I. The data reveal a decline in oxygen uptake as the concentration of this compound is increased. This is more pronounced when glutamate or P-hydroxybutyrate acts as substrate. It is noteworthy that there is no concurrent reduction in P: 0 values with increasing concentrations of phenethylbiguanide. These data stand in sharp contrast to those presented in Table II where the effects of increasing concentrations of chlorpropamide, 1-propyl-3-(p-chlorobenzenesulfonyl) urea, are seen. Here P: O values are progressively diminished with inoreasing concentrations of this compound, and there is no depression of oxygen uptake except at 3 X lo+ M with glutamate as substrate. Reversal of Inhibition of Oxidation Produced by Phenethyl-biguanide-The data in Table III show that addition of 2, 4-dinitrophenol at lOA M, salicylate at 3 X 10m3 M, or chlorpropamide at 3 X 10-3~ completely overcomes inhibition of glutamate oxidation produced by lo-3 M phenethylbiguanide. On the other hand, the data reveal that addition of phenethylbiguanide inhibits stimulation of glutamate oxidation resulting from addition of 2, 4-dinitrophenol, salicylate, or chlorpropamide. Similar findings are noted when P-hydroxybutyrate or succinate oxidation are studied.