Metabolism: Sweet enticements to move

Abstract

The formation of new blood vessels from pre-existing ones is a carefully orchestrated dance. A study reveals that the metabolism of sugar by glycolysis contributes to its regulation.

Figure 1. Glycolysis regulates angiogenesis

The formation of new blood vessels involves the outward movement of endothelial cells from the lining of existing blood vessels, a process that relies on the rapid reorganization of actin-protein filaments in cellular structures called filopodia and lamellipodia (not shown). The energy for this (in the form of ATP) is provided by the breakdown of glucose, but endothelial cells are unusual in that the pyruvate produced by glycolysis is converted to lactate, rather than being channelled into mitochondria for further oxidation, as occurs in most cells. De Bock et al. show that both angiogenesis and glycolysis are accelerated by the activity of the enzyme PFK2 in endothelial-cell lamellipodia and filopodia. PFK2 converts the glycolytic intermediate fructose-6-phosphate (F-6-P) into fructose-2,6-bisphosphate (F-2,6-P₂), which, in turn, enhances the activity of the glycolytic enzyme PFK1, thereby accelerating glycolysis at these sites. Pyruvate then leaves the cell as lactate, probably because filopodia and lamellipodia are too small to accommodate mitochondria.