FACTORS AFFECTING THE ACTIVITY OF ALLOXANIN VITRO

Abstract

The effect of alloxan on the oxygen uptake and the succinic dehydrogenase activity of rat liver homogenates has been studied in an attempt to gain some insight into the activity of alloxan within the cell. The increased oxygen uptake on the addition of alloxan to liver homogenates was found to be non-enzymatic in nature and to depend on some heat stable factor or factors in the preparation. The ability of reduced glutathione to substitute for the homogenate suggests that this substance may be concerned. It is thought that alloxan is reduced to dialuric acid by a number of factors in the homogenate, and that the increased oxygen uptake results from the spontaneous reoxidation of this latter substance. Experiments with dialuric acid tend to confirm this hypothesis. The inactivation of succinic dehydrogenase by alloxan is greatly influenced by the pH of the solution in which the alloxan is dissolved, as well as by the pH of the enzyme preparation, with acidity increasing and alkalinity decreasing the effect. The progressive nature of the inactivation with time is shown to depend upon the lowering of the pH which is brought about by the addition of alloxan to an unbuffered enzyme mixture. The experimental results are discussed in relation to the possible importance of pH in the selective toxicity of alloxan.