Which enzymatic feature best distinguishes the phosphofructokinase-1 (PFK-1) catalysed reaction from the hexokinase-catalysed reaction in glycolysis?

Explanation

## Distinguishing Features of Hexokinase vs PFK-1 ### Hexokinase Reaction (Step 1) - Catalyses: Glucose + ATP → Glucose-6-phosphate + ADP - **Not** the rate-limiting step of glycolysis - Constitutive enzyme; minimal allosteric regulation - Reversible under physiological conditions (though thermodynamically favoured) - Traps glucose in the cell (G6P cannot cross membrane) ### PFK-1 Reaction (Step 3) - Catalyses: Fructose-6-phosphate + ATP → Fructose-1,6-bisphosphate + ADP - **The committed step** of glycolysis — once formed, F-1,6-BP is committed to glycolysis - **Rate-limiting enzyme** of the entire pathway - Extensively allosterically regulated (see table below) - Irreversible under cellular conditions (ΔG << 0) ### Allosteric Regulation of PFK-1 | Regulator | Effect | Mechanism | |-----------|--------|----------| | ATP | Inhibition | Signals energy sufficiency | | AMP / ADP | Activation | Signals energy depletion | | Citrate | Inhibition | Signals sufficient biosynthetic precursors | | F-2,6-BP | Activation | Most potent activator; fed state signal | | pH ↓ | Inhibition | Lactate accumulation inhibits glycolysis | **Key Point:** PFK-1 is the **primary control point** of glycolysis. Its allosteric regulation allows the cell to rapidly switch between glycolytic flux and gluconeogenesis based on energy and metabolic state. Hexokinase, by contrast, is a housekeeping enzyme with minimal feedback control. **High-Yield:** In NEET PG, expect questions linking PFK-1 regulation to metabolic states: - **Fed state (high F-2,6-BP)** → PFK-1 active → glycolysis ↑ - **Fasted state (low F-2,6-BP)** → PFK-1 inhibited → gluconeogenesis ↑ **Mnemonic:** **PFK = Primary Flux Kinase** — it controls the committed, rate-limiting step.