## Glycolysis Regulation: The Rate-Limiting Step **Key Point:** Phosphofructokinase-1 (PFK-1) catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate and is the primary rate-limiting enzyme of glycolysis. ### Why PFK-1 is the Committed Step While hexokinase catalyzes the first step (glucose → glucose-6-phosphate), glucose-6-phosphate is a branch point that can enter glycolysis, glycogen synthesis, or the pentose phosphate pathway. PFK-1 catalyzes an irreversible reaction that commits the carbon skeleton specifically to glycolysis. ### Allosteric Regulation of PFK-1 | Regulator | Effect | Mechanism | | --- | --- | --- | | ATP | Inhibition | Signals energy sufficiency | | AMP / ADP | Activation | Signals energy depletion | | Citrate | Inhibition | Signals adequate biosynthetic precursors | | Fructose-2,6-bisphosphate | Activation | Most potent activator; fed state signal | | H⁺ | Inhibition | Acidosis suppresses glycolysis | **High-Yield:** PFK-1 is the most heavily regulated enzyme in glycolysis and is the textbook example of allosteric control in biochemistry exams. **Mnemonic:** **"PFK is the COMMITTED step"** — it is the first irreversible step unique to glycolysis, not shared with other pathways.
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