Which is the most common rate-limiting enzyme of glycolysis?

Explanation

## Rate-Limiting Enzyme of Glycolysis **Key Point:** Phosphofructokinase-1 (PFK-1) is the primary rate-limiting and most highly regulated enzyme of glycolysis. It catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, the first committed step of the pathway. ## Why PFK-1 is the Rate-Limiting Step 1. **Irreversible reaction** — catalyzes the first committed step unique to glycolysis (hexokinase is shared with other pathways) 2. **Highly regulated** — subject to allosteric regulation by multiple metabolites 3. **Energetically unfavorable** — requires ATP and is the main control point ## Regulation of PFK-1 | Regulator | Effect | Mechanism | |-----------|--------|----------| | ATP | Inhibition | Allosteric inhibitor (signals energy sufficiency) | | AMP / ADP | Activation | Allosteric activators (signals energy depletion) | | Citrate | Inhibition | Allosteric inhibitor (signals biosynthetic precursors available) | | Fructose-2,6-bisphosphate (F-2,6-BP) | Activation | Most potent activator; increases affinity for F-6-P | | pH | Inhibition | Low pH inhibits PFK-1 (Pasteur effect in anaerobic conditions) | **High-Yield:** PFK-1 is the **primary control point** of glycolysis. Questions on glycolytic regulation almost always center on PFK-1 allosteric control. **Clinical Pearl:** In anaerobic conditions (lactic acidosis), decreased pH inhibits PFK-1, slowing glycolysis — a protective mechanism to prevent further lactate accumulation. **Mnemonic:** **PFK = Primary Flux Keeper** — it gates the entry of glucose into the committed glycolytic pathway.