Inhibition of hexose and glycerol utilization by 2-deoxy-d-glucose in Trypanosoma gambiense and Trypanosoma rhodesiense

Abstract

It was shown that 2-deoxy-d-glucose (D-2-D) inhibited the fermentation of glucose, mannose, fructose, and glycerol by Trypanosoma gambiense. Evidence is presented that shows D-2-D inhibits metabolism at two sites at least within the Embden-Meyerhof-Parnas pathway. The inhibition of both hexose and glycerol utilization by D-2-D was reversed by the addition of glucose; however, inhibition of glycerol utilization was much more sensitive to reversal. A second analogue of glucose, glucosamine, was also capable of inhibiting glycerol utilization but had no apparent effect on the fermentation of glucose. The structural requirements of compounds capable of acting as inhibitors of hexose and glycerol utilization as well as those compounds capable of relieving glycerol inhibition were shown to be highly specific. At present, the exact enzymatic sites inhibited by either D-2-D or glucosamine are unknown. However, the possibility that D-2-D inhibits the transport of substrates across the cell membrane is discussed.