The catabolism of glucose by strains of Trypanosoma rhodesiense

Abstract

Glucose is an essential substrate for survival of the African trypanosome, T. rhodesiense, in vitro. Uniformly C14-labeled glucose was used to prepare a radiocarbon balance of the products of this catabolism. Under aerobic conditions, pyruvate and, to a lesser extent, glycerol were the main end products; only minor amounts of C14 were incorporated into succinate, respiratory CO2 and cell material. Approximately equal amounts of pyruvate and glycerol and the amount of C14O2 evolved when the trypanosome was incubated with (U-C14)- or (3:4-C142)- or (1-C14)-glucose was consistent with the view that the Embden-Meyerhof-Parnas scheme is the major if not the only pathway of glucose utilization in vitro. Similar studies with (1-C14) glucose were made with the drug-resistant variants of this strain and with a new strain isolated from a human patient. Pyruvate and glycerol formed from (1-C-14)-glucose under aerobic conditions have equal molar radioactivities. In contrast, glycerol has a greater molar radioactivity than pyruvate under anaerobic condition. The implications of these results are discussed. The further metabolism of pyruvate was studied by comparing the radioactivities in fractions or compounds isolated after incubation of the trypanosome with (U-C14) glucose or (2-C14) acetate or NaHC14O3. It is concluded that CO2 fixation, leading to the direct synthesis of oxalacetate from pyruvate and the reduction of the former compound, can account for the formation of succinate. Abnormally high blood-pyruvate levels of infected rats are correlated with the degree of infection. These levels rapidly return to normal with treatment of the host with a trypanocidal drug. It thus seems probable that the amount of pyruvate produced by the parasite is greater than the capacity of the host to metabolize or excrete it.