Regarding the Cori cycle and lactate metabolism, all of the following statements are true EXCEPT:

Explanation

## Cori Cycle: Overview and Mechanism The Cori cycle (lactate cycle) is a metabolic pathway that shuttles lactate from peripheral tissues (especially muscle) back to the liver for gluconeogenesis, maintaining blood glucose during fasting or exercise. ### Correct Statements (Options 0, 1, 2) **Key Point:** Option 0 is correct — lactate produced during anaerobic glycolysis in muscle is transported via blood to the liver. **Key Point:** Option 1 is correct — LDH catalyzes the reversible reaction: Pyruvate + NADH ↔ Lactate + NAD^+^ in both tissues. **Key Point:** Option 2 is correct — the liver converts lactate back to glucose via gluconeogenesis (lactate → pyruvate → oxaloacetate → phosphoenolpyruvate → glucose), which is released into blood for muscle uptake. ### Why Option 3 is WRONG **High-Yield:** The conversion of lactate to glucose in the liver is **energetically COSTLY**, not favorable. It requires: - Lactate → Pyruvate (via LDH, no ATP cost) - Pyruvate → Oxaloacetate (via pyruvate carboxylase, **1 ATP**) - Oxaloacetate → Phosphoenolpyruvate (via PEPCK, **1 GTP**) - Subsequent steps to glucose (**2 more GTP**) **Total: ~4 high-energy phosphate bonds consumed per glucose made from 2 lactate molecules.** This is **energetically unfavorable** for the liver — it is a **cost** of gluconeogenesis, not a benefit. The liver performs this cycle to maintain blood glucose for the brain and RBCs, not for energy gain. **Clinical Pearl:** During intense exercise or sepsis, lactate accumulation and the Cori cycle become a major source of hepatic glucose production, sustaining blood glucose despite muscle not taking up glucose. ### Summary Table | Aspect | Muscle | Liver | |--------|--------|-------| | Lactate source | Anaerobic glycolysis | Uptake from blood | | LDH reaction | Pyruvate → Lactate | Lactate → Pyruvate | | Gluconeogenesis | No | Yes (energy-expensive) | | Net ATP effect | Gains ATP (anaerobic) | Loses ATP (gluconeogenesis) | [cite:Lehninger Principles of Biochemistry Ch 20]