Which glycolytic enzyme is allosterically inhibited by ATP and citrate, and activated by AMP and ADP?

Explanation

## Allosteric Regulation of Glycolytic Enzymes **Key Point:** Phosphofructokinase-1 (PFK-1) catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate and is the rate-limiting enzyme of glycolysis. It is the primary site of allosteric regulation in the pathway. ### Allosteric Inhibitors of PFK-1 - **ATP** — signals high energy status; inhibits glycolysis - **Citrate** — indicates sufficient acetyl-CoA for TCA cycle; inhibits glycolysis - **H⁺ and Pi** — products of energy metabolism; inhibit PFK-1 ### Allosteric Activators of PFK-1 - **AMP** — signals low energy status; activates glycolysis - **ADP** — signals ATP depletion; activates glycolysis - **Fructose-2,6-bisphosphate (F-2,6-BP)** — most potent activator; increases PFK-1 affinity for substrate **High-Yield:** PFK-1 is called the "committed step" of glycolysis because F-6-P can enter other pathways (pentose phosphate pathway, glycogen synthesis), but F-1,6-BP is committed to glycolysis. **Clinical Pearl:** Deficiency of PFK-1 (Glycogen Storage Disease Type VII, Tarui disease) causes exercise intolerance, myalgia, and rhabdomyolysis because muscles cannot generate ATP from glucose during contraction. **Mnemonic:** **CATP** — **C**itrate and **ATP** inhibit PFK-1; **AAMP** — **AMP** and **ADP** activate PFK-1.