Describe the Cori cycle and its significance. Add a note on the glucose–alanine cycle.
Definition
Cori cycle (lactic acid cycle) = the cycle in which lactate produced by anaerobic glycolysis in muscle and RBC is carried to the liver, converted back to glucose, and returned to those tissues.
The Cycle
Muscle / RBC: glucose → 2 lactate (2 ATP gained) → Lactate enters blood → liver → Lactate → pyruvate → gluconeogenesis (6 ATP spent) → Glucose released into blood → Returns to muscle and RBC
Energetics
| Tissue | ATP change | Comment |
|---|---|---|
| Muscle / RBC | +2 ATP gained | Rapid, oxygen independent |
| Liver | −6 ATP spent | Uses ATP from fatty acid oxidation |
| Net for the body | −4 ATP | A deliberate, useful loss |
CLINICAL PEARL
The cycle costs the body energy, and that is the point. It shifts the metabolic burden from muscle, which needs ATP urgently, to the liver, which has plenty from fat oxidation. It also clears lactate that would otherwise cause acidosis.
Significance
- Prevents lactic acidosis by removing lactate from the blood
- Allows muscle to continue working anaerobically during intense exercise
- Salvages carbon that would otherwise be lost
- Supplies glucose to RBC, which produce lactate continuously since they have no mitochondria
- Accounts for a significant part of the oxygen debt after exercise
The Glucose–alanine Cycle (compare)
Muscle: pyruvate + amino group → alanine (transamination) → Alanine to liver → Liver: alanine → pyruvate + NH3 → Pyruvate → glucose; NH3 → urea → Glucose returns to muscle
- Carries both carbon and nitrogen to the liver, whereas the Cori cycle carries carbon only
- Prominent in starvation, when muscle protein is being broken down
Applied Aspects
- Lactic acidosis results when lactate production exceeds hepatic clearance — in shock, hypoxia, sepsis, and in liver failure, where the cycle itself fails
- Metformin inhibits hepatic gluconeogenesis and so impairs lactate clearance → contraindicated in renal and hepatic failure
- Serum lactate is a marker of tissue hypoperfusion and is used to gauge the severity of shock and the response to resuscitation
- The cycle is named after Carl and Gerty Cori, who received the Nobel Prize in 1947
- In prolonged starvation the glucose–alanine cycle predominates, because muscle protein rather than glycogen is being consumed
All questions in Carbohydrate Metabolism I: Glycolysis, TCA & Gluconeogenesis
- Q1Define glycolysis. Describe its reactions, energetics and regulation. Add a note on its significance in the red blood cell. ★
- Q2Describe the reactions of the TCA cycle with its energetics and regulation. Explain its amphibolic role and add a note on anaplerotic reactions. ★
- Q3Define gluconeogenesis. Describe its substrates, the key enzymes bypassing glycolysis, and its regulation. ★
- Q4Describe the sources and fates of blood glucose. Explain the hormonal regulation of blood glucose in the fed and fasting states. ★
- Q5Describe the pyruvate dehydrogenase complex with its components, coenzymes and regulation. Explain its metabolic significance. ★
- SN1Describe the Cori cycle and its significance. Add a note on the glucose–alanine cycle. ★
- SN2Describe the Rapoport–Luebering shunt and the significance of 2,3-BPG. ★
- SN3Define substrate-level phosphorylation. Give the reactions and compare it with oxidative phosphorylation. ★
- SN4Define anaplerotic reactions. Give examples and explain their importance. ★
- SN5Classify the glycogen storage diseases. Describe Von Gierke and McArdle disease. ★
- SN6Define lactic acidosis. Describe its biochemical basis and classify its causes. ★
- SN7Describe the glucose transporters with their sites and functions.