Controlling Turbocharged Glycolysis

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Science  17 Mar 2000:
Vol. 287, Issue 5460, pp. 1889
DOI: 10.1126/science.287.5460.1889g

Metabolism of glucose requires an initial investment of two ATPs, used to doubly phosphorylate the six-carbon skeleton, in order to reap a harvest of four ATPs on the way to two molecules of pyruvate. This arrangement runs the risk of creating a positive feedback loop unless the hexose kinase enzymes are allosterically regulated, as they are in most organisms. There is, however, no such regulation of these enzymes in trypanosomes (the causative agent of sleeping sickness), although they do contain an unusual organelle known as the glycosome that compartmentalizes the enzymes of glycolysis.

Using quantitative models of metabolism based on experimentally determined kinetic parameters, Bakker et al. now suggest that the presence of this organelle serves to regulate ATP and hexose phosphate concentrations. Within the glycosome, total phosphate is fixed, which functions to brake the initial glycolytic steps as hexose phosphate accumulates. Furthermore, these pools of phosphorylated intermediates provide a primed start for the organism to recover from a period of glucose starvation. Neither of these regulatory mechanisms were observed in a trypanosome modeled with the same enzyme parameters but lacking the glycosomal compartment.—GJC

Proc. Natl. Acad. Sci. U.S.A.97, 2087 (2000).

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