Gluconeogenesis and Cori cycle

 1. Introduction

• It is the synthesis of glucose from non-carbohydrate compounds (e.g. pyruvate, lactate, glycerol etc).
• In contrast, the synthesis of glucose from carbohydrate source- glycogen is called Glycogenolysis.
• Gluconeogenesis occurs in cytosol of liver cells mainly; and renal cortex up to a lesser extent.

2. Importance of Gluconeogenesis

• Glucose is very essential for the body. It not only is a source of energy but it is a precursor for some other compounds too. We obtain glucose mainly from three sources:
• food in the form of carbohydrate
• from the breakdown of glycogen (Glycogenolysis)
• gluconeogensis in liver
• Although there are other sources of energy e.g. fats, lipids etc, some of the body parts (like brain, erythrocytes, kidney medulla, testes) are dependent on glucose only.
• Under fasting condition, it is essential to meet the need of body for glucose.
• Under anaerobic condition, glucose is the only source of energy in skeletal muscle.
• Other carbohydrate are also synthesized from glucose e.g. lactose.
• Glucose is converted into glycerol and utilized for the synthesis of fats.

3. Glycolysis Vs Gluconeogenesis

• Gluconeogenesis is basically reverse of the glycolysis.
• There are total 10 steps in the glycolytic pathway.
• 7 of the 10 enzymatic reactions of glycolysis are reversible and are exactly same in gluconeogenesis with opposite direction.
• However, 3 reactions of glycolysis are irreversible, which are different in both the pathways, and those 3 reactions in glycolysis are catalyzed by-
• Hexokinase (First step)
• Phosphofructokinase (Third step).
• Pyruvate kinase (Last step).

4. Pathway of gluconeogenesis

• Here in the following pathway, the comparative features of glycolysis and gluconeogenesis have been shown.
• The left pathway (pink colored) represents the glycolysis; and the right pathway (blue colored) represents the gluconeogenesis.

Note: In the examination, while answering gluconeogenesis one should start with pyruvate and going downward up to glucose in the final step; rather than starting with glucose with upward arrow. 

5. Overall summary of pathway

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2H⁺ + 4 H2O è Glucose + 4 ADP + 2 GDP + 6 Pi + NAD⁺

6. Gluconeogenesis from lactate (Cori cycle)

• Under anaerobic conditions, pyruvate is converted into lactate (as discussed in glycolysis).
• But, lactate produced in the muscles cannot be utilized for gluconeogenesis there, because muscle lacks enzymes- glucose 6-phosphatase and fructose 1,6-bisphosphatase.
• Hence, lactate is carried from skeletal muscle to blood and handed over to liver.
• Inside liver, it is oxidized to pyruvate, then converted to glucose.
• Then, glucose is transported to skeletal muscles.
• This is called as Cori cycle (or Lactic acid cycle).