Which enzyme regulates glycolysis by converting fructose-6-phosphate to fructose-1,6-bisphosphate, committing glucose to glycolysis?

• A. Hexokinase
• B. Phosphofructokinase-1 (PFK-1)
• C. Pyruvate kinase
• D. Aldolase

Answer: (B)

The regulation of glycolysis centers on the committed step where fructose-6-phosphate is converted to fructose-1,6-bisphosphate by phosphofructokinase-1. This reaction uses ATP and is essentially irreversible under physiological conditions, so it gates whether glucose-derived carbons enter glycolysis. Because of that, PFK-1 acts as the major control point, directing flux according to the cell’s energy needs. It’s allosterically regulated: when the cell needs energy, AMP/ADP and fructose-2,6-bisphosphate activate PFK-1 to speed glycolysis; when energy is plentiful, ATP and citrate inhibit it to prevent wasteful ATP use. Hormonal signals also influence this through the production of fructose-2,6-bisphosphate, linking glycolytic throughput to feeding state.

In contrast, the initial step that traps glucose as glucose-6-phosphate does not commit carbons exclusively to glycolysis, since glucose-6-phosphate can enter other pathways like the pentose phosphate pathway. The last step producing pyruvate and the enzyme that splits the six-carbon sugar into two triose phosphates occur later and do not set the primary regulatory gate.