Graduate Thesis Or Dissertation
 

The effect of 2-deoxyglucose on hexose metabolism in Saccharomyces cerevisia

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  • The inhibitory effect of 2-deoxy-D-glucose (2-DG) upon the metabolism of glucose and fructose by proliferating cells of Saccharomyces cerevisiae (OSU strain 2) has been examined. By the use of radiotracer methods, particularly radiorespirometric techniques, it has been possible to demonstrate that the rate of hexose assimilation by yeast cells is reduced significantly when 2-DG is present in the incubation medium. This can be attributed to the inhibitory effect of 2-DG upon permeation of either glucose or fructose into yeast cells. It appears that, when 2-DG and substrate hexose are in the medium, 2-DG is preferentially permitted into the cells and converted to 2-DG-6-P, thereby depleting most of the available ATP, which is of vital importance to the transport of hexoses into yeast cells. When 2-DG is present in the medium at lower concentrations, despite the fact that the rate of hexose transport is reduced, complete utilization of substrate hexose, administered in a single dose, can still be realized. By examining data of radiorespirometric experiments, one finds that substrate glucose or fructose has been routed to a relatively greater extent into catabolic pathways in the presence of 2-DG, and participation of the anabolic pathway is correspondingly reduced. However, it does not appear that the relative participation of individual pathways, for that portion of substrate glucose engaged in catabolism, has been altered to any great extent. When fructose is used as the sole carbon source, relative participation of catabolic pathways has been altered by the presence of 2-DG in the medium. This has been attributed to the inhibitory effect of 2-DG exerted on the enzymic reaction, catalyzed by phosphohexoisomerase, which is responsible for conversion of fructose-6-P to glucose-6-P. However, at low substrate levels of fructose, in the absence of 2-DG, the relative participation of catabolic pathways is also altered, presumably due to a necessity for saturation of glycolytic enzymes, before equilibration between fructose-6-P and glucose-6-P is achieved.
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