FIGURE 5.

Schematic of glycolysis and ancillary glucose metabolism pathways. Once glucose enters the cell, it can be phosphorylated to form glucose-6-phosphate (G6P), which isomerizes to fructose-6-phosphate (F6P). The F6P is then phosphorylated by PFK1—the major rate-limiting and committed step in glycolysis—to fructose-1,6-bisphosphate (F-1,6-P₂). These reactions comprise the preparatory phase of glycolysis and utilize ATP. In addition, glycolytic metabolites in this phase of glycolysis serve as precursors to several ancillary biosynthetic pathways, including the PPP and the hexosamine biosynthetic pathway (HBP), as well as the polyol pathway (not shown) and glycogen synthetic pathway (not shown). The payoff phase commences with the splitting of fructose-1,6-bisphosphate into DHAP and GAP. DHAP is a precursor for the GLP, important for the synthesis of glycerophospholipids, and it can be isomerized to GAP. GAP is oxidized and phosphorylated to 1,3-bisphosphoglycerate. Energy (ATP) is released as these 1,3-bisphosphoglycerate molecules are converted to pyruvate, which is then transaminated to alanine, converted to lactate, or oxidized in mitochondria. The activity of PFK1, which sits at the nexus between the preparatory and payoff phases, is increased by the product of 6-phosphofructo-2-kinase (PFK2), fructose-2,6 bisphosphate (F-2,6-P₂).