Cytosolic 10-step pathway converting glucose to pyruvate with net 2 ATP + 2 NADH. Three irreversible regulatory steps: hexokinase / glucokinase (hexokinase IV in liver) — glucose phosphorylation; phosphofructokinase-1 (PFK-1) — RATE-LIMITING, allosterically inhibited by ATP + citrate, activated by AMP + F-2,6-BP; pyruvate kinase — final step, allosterically inhibited by ATP + alanine. Tumor cells exhibit aerobic glycolysis (Warburg effect) — high glycolytic flux even with O2 available, supporting biomass over ATP yield. PKM2 isoform dimer/tetramer switching is a major Warburg switch.
Organ Systems
endocrine
nervous
Pathway Steps
glucose → glucose-6-phosphate — via hexokinase (HK1-4) — glucokinase (HK4) in liver/β-cell. Hexokinase (HK1–3) has low Km and is product-inhibited by glucose-6-phosphate, clamping uptake; the liver/β-cell isoform glucokinase (HK4) has high Km and no G6P inhibition, acting as a glucose sensor that scales flux with blood glucose. Phosphorylation also traps glucose in the cell — charged G6P cannot cross the membrane.
glucose-6-phosphate → fructose-1-6-bisphosphate — via phosphofructokinase-1 (PFK-1) — RATE-LIMITING. PFK-1 is the committed, rate-limiting and principal regulatory step: allosterically inhibited by ATP and citrate (energy/carbon abundance) and activated by AMP and fructose-2,6-bisphosphate — the latter set by insulin/glucagon via PFK-2 — integrating glycolysis with the cell’s energy state and hormones.
fructose-1-6-bisphosphate → pyruvate — via multi-step (aldolase + TPI + GAPDH + PGK + PGM + enolase + PYRUVATE KINASE). Payoff phase: aldolase splits F1,6BP into two triose phosphates (interconverted by TPI), then GAPDH→PGK→PGM→enolase→pyruvate kinase produce 4 ATP and 2 NADH (net 2 ATP per glucose after the priming phase). Pyruvate kinase is the third regulated step; GAPDH couples flux to NAD⁺ regeneration.