All of the following are true regarding the energetics and regulation of glycolysis EXCEPT:

Explanation

## Glycolytic Energetics and Allosteric Regulation ### Statement-by-Statement Analysis | Statement | Content | Accuracy | |-----------|---------|----------| | 1 | Hexokinase reaction is irreversible | ✓ Correct | | 2 | PFK-1 inhibited by high ATP:AMP | ✓ Correct | | 3 | Pyruvate dehydrogenase activated by acetyl-CoA, NADH | ✗ **WRONG** | | 4 | Net yield: 2 ATP, 2 NADH per glucose (anaerobic) | ✓ Correct | ### The Critical Error: Pyruvate Dehydrogenase Regulation **Key Point:** Pyruvate dehydrogenase complex (PDC) is **INHIBITED** (not activated) by high concentrations of its products: acetyl-CoA and NADH. This is a classic example of **product inhibition** and **feedback regulation**. **High-Yield:** PDC Regulation — **Inhibitors vs. Activators** **Inhibitors (Products):** - Acetyl-CoA (product) - NADH (product) - ATP (energy signal) **Activators (Substrates/Cofactors):** - Pyruvate (substrate) - CoA (cofactor) - NAD^+^ (cofactor) - ADP, AMP (energy depletion signals) - Ca^2+^ (allosteric activator in muscle) **Clinical Pearl:** This inhibition makes physiological sense — when the cell has abundant acetyl-CoA and NADH (indicating sufficient energy and biosynthetic precursors), there is no need to further oxidize pyruvate. Conversely, when pyruvate accumulates and NAD^+^ is available, the enzyme is active. ### Why the Other Statements Are Correct **Statement 1: Hexokinase Irreversibility** - Glucose + ATP → G6P + ADP (ΔG°' = −16.7 kJ/mol) - Large negative ΔG makes it thermodynamically irreversible - Cannot be reversed by phosphatase under normal conditions **Statement 2: PFK-1 Inhibition by ATP:AMP** - High ATP:AMP ratio = abundant energy - PFK-1 is allosterically inhibited by ATP and citrate - This prevents futile cycling and excess glycolysis - Conversely, AMP and ADP activate PFK-1 **Statement 4: Net ATP and NADH Yield** - Substrate-level phosphorylation: 2 ATP (from 1,3-BPG and PEP steps) - Oxidation of 2 G3P → 2 pyruvate: 2 NADH - Net: 2 ATP + 2 NADH per glucose (anaerobic: NADH is regenerated via lactate formation) **Mnemonic:** **PDC Inhibitors = PAC** (Products: Acetyl-CoA; ATP; Citrate) — remember that products shut down the enzyme, not activate it.