GLUCONEOGENESIS & CORI CYCLE_241223_100224

Summary of Notes: Gluconeogenesis and Cori’s Cycle

Gluconeogenesis

• Definition: The process of synthesizing glucose from non-carbohydrate precursors like lactate, glycerol, and amino acids (e.g., alanine).

• Location: Mainly occurs in the liver during fasting to maintain blood glucose levels.

• Substrates: Lactate, glycerol, alanine, and intermediates from the TCA cycle (e.g., oxaloacetate).

• Key Points:

  • Not a complete reversal of glycolysis.

  • Circumvents irreversible steps of glycolysis using enzymes like pyruvate carboxylase, PEPCK, fructose-1,6-bisphosphatase, and glucose-6-phosphatase.

  • Essential for tissues like the brain and RBCs that depend on glucose.

Steps of Gluconeogenesis

1. Formation of intermediates from carbon sources.

2. Conversion of pyruvate to phosphoenolpyruvate (PEP) via oxaloacetate in mitochondria.

3. Conversion of glycerol to gluconeogenic intermediates.

Regulation

• Hormonal Regulation:

  • Glucagon and glucocorticoids stimulate gluconeogenesis.

  • Insulin inhibits gluconeogenesis.

• Reciprocal regulation with glycolysis ensures only one pathway is active at a time.

Cori’s Cycle

• Also known as the lactic acid cycle.

• Occurs between muscles and the liver:

  1. In muscle, pyruvate is converted to lactate due to lack of oxygen during exercise.

  2. Lactate is transported to the liver, oxidized to pyruvate, and converted to glucose via gluconeogenesis.

  3. The glucose returns to muscle to be utilized for energy.

• Prevents lactate accumulation in muscles, which could cause cramps.

Medical Note

• Glucocorticoids, produced during stress, stimulate muscle protein degradation to provide substrates for gluconeogenesis.

• High doses of synthetic glucocorticoids (e.g., dexamethasone) can elevate blood glucose levels and weaken muscles due to enhanced gluconeogenesis.