Cori cycle

Source: Wikipedia, the free encyclopedia.
Not to be confused with
Cori disease
.
Cori cycle

The Cori cycle (also known as the lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori,[1] is a metabolic pathway in which lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate.[2]

Process

Carl Cori and Gerty Cori jointly won the 1947 Nobel Prize in Physiology or Medicine
, for their discovery of the course of the catalytic conversion of glycogen, of which the Cori cycle is a part.

Muscular activity requires

pyruvate, one product of glycolysis, into the citric acid cycle, which ultimately generates ATP through oxygen-dependent oxidative phosphorylation
.

When oxygen supply is insufficient, typically during intense muscular activity, energy must be released through

fermentation
for the details.)

Instead of accumulating inside the muscle cells, lactate produced by anaerobic fermentation is taken up by the

bloodstream; it is ready to be fed into further glycolysis reactions. If muscle activity has stopped, the glucose is used to replenish the supplies of glycogen through glycogenesis.[3]

Overall, the glycolysis steps of the cycle produce 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis steps. Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules in the Cori cycle shifts the

metabolic
burden from the muscles to the liver.

Significance

The cycle's importance is based on preventing lactic acidosis during anaerobic conditions in the muscle. However, normally, before this happens, the lactic acid is moved out of the muscles and into the liver.[3]

Additionally, this cycle is important in ATP production, an energy source, during muscle exertion. The end of muscle exertion allows the Cori cycle to function more effectively. This repays the oxygen debt so both the electron transport chain and citric acid cycle can produce energy at optimum effectiveness.[3]

The Cori cycle is a much more important source of substrate for gluconeogenesis than food.[4][5] The contribution of Cori cycle lactate to overall glucose production increases with fasting duration before plateauing.[6] Specifically, after 12, 20, and 40 hours of fasting by human volunteers, gluconeogenesis accounts for 41%, 71%, and 92% of glucose production, but the contribution of Cori cycle lactate to gluconeogenesis is 18%, 35%, and 36%, respectively.[6] The remaining glucose production comes from protein breakdown,[6] muscle glycogen,[6] and glycerol from lipolysis.[7]

The drug metformin can cause lactic acidosis in patients with kidney failure because metformin inhibits the hepatic gluconeogenesis of the Cori cycle, particularly the mitochondrial respiratory chain complex 1.[8] The buildup of lactate and its substrates for lactate production, pyruvate and alanine, lead to excess lactate.[9] Normally, the excess acid that is the result of the inhibition of the mitochondrial chain complex would be cleared by the kidneys, but in patients with kidney failure, the kidneys cannot handle the excess acid. A common misconception posits that lactate is the agent responsible for the acidosis, but lactate is a conjugate base, being mostly ionised at physiologic pH, and serves as a marker of associated acid production rather than being its cause. [10] [11]

See also

References

  1. ^ "Carl and Gerty Cori and Carbohydrate Metabolism". National Historic Chemical Landmark. American Chemical Society. 2004. Retrieved 12 May 2020.
  2. ISBN 978-0-7167-4339-2
    .
  3. ^ a b c "Ophardt CE (2003). "Cori Cycle". Virtual Chem Book. Elmhurst College. pp. 1–3. Archived from the original on 23 April 2008. Retrieved 3 May 2008.
  4. PMID 11213896
    .
  5. S2CID 24330397
    .
  6. ^
    PMID 9725823
    .
  7. PMID 16848698
    .
  8. S2CID 23259898
    .
  9. PMID 7862618
    .
  10. ^ "The myth of lactic acidosis".
  11. ^ "Metformin toxicity".

Further reading

  • Smith AD, Datta SP, Smith GH, Campbell PN, Bentley R, eds. (1997). Oxford Dictionary of Biochemistry and Molecular Biology. New York: Oxford University Press.
    ISBN 978-0-19-854768-6
    .
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