Gluconeogenesis 

Gluconeogenesis is the metabolic process that generates glucose from non-carbohydrate sources, including lactate, pyruvate, intermediates of the citric acid cycle, and most amino acids. This process primarily occurs in the liver and, to a lesser extent, in the kidneys. It becomes especially active when dietary carbohydrate intake is insufficient.

1.0Precursors for Gluconeogenesis

• Lactate: It is produced from pyruvate during the glycolysis process. The lactate is transferred to the liver by "CORI'S cycle" and converted to glucose.
• Glycerol : Glycerol is produced in adipose tissue through the hydrolysis of triacylglycerol. However, adipose tissue cannot effectively utilize the generated glycerol due to its low content of the enzyme glycerol kinase. Consequently, glycerol is transported to the liver, where it is converted into glucose.
• Glucogenic Amino Acid : The glucogenic amino acids' carbon skeleton is converted to pyruvate, which converts to glucose.
• Intermediate of TCA cycle 

2.0Location

Gluconeogenesis occurs mainly in the cytosol.

3.0Characteristics of Gluconeogenesis

• It involves glycolysis, TCA cycle and some particular reactions.
• Glycolysis and Gluconeogenesis share the same pathway but in opposite directions.
• Special reactions are catalyzed by Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase, Fructose 1-6 bisphosphatase and Glucose-6-phosphatase.

4.0Reactions of Gluconeogenesis

While many gluconeogenesis reactions reverse those of glycolysis, there are specific steps unique to this pathway:

1. Conversion of pyruvate to phosphoenolpyruvate: Pyruvate is initially converted to oxaloacetate, which then becomes phosphoenolpyruvate.

2. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate.

3. Formation of glucose from glucose 6-phosphate.

1. Conversion of pyruvate to phosphoenolpyruvate: In this step pyruvate is first converted to oxaloacetate, which is then converted to phosphoenolpyruvate. 

• Oxaloacetate, synthesized within the mitochondria, needs to relocate to the cytosol for conversion into phosphoenolpyruvate, facilitated by the enzyme phosphoenolpyruvate kinase found in the cytosol. Since oxaloacetate cannot freely diffuse across the mitochondrial membrane, it undergoes conversion into malate, which can cross into the cytosol. 
• In the cytosol, malate is converted back into oxaloacetate. Alternatively, oxaloacetate within the mitochondria can combine with acetyl coenzyme A to form citrate, which is permeable to the mitochondria. In the cytosol, citrate reverts to oxaloacetate. Once phosphoenolpyruvate is generated, it enters the reverse glycolytic pathway to produce fructose 1,6-bisphosphate.

2. Conversion of fructose 1, 6, bisphosphate to fructose six phosphates:

3. Formation of glucose from glucose 6 phosphate: 

• Glucose produced by gluconeogenesis in the liver or kidney is released into the bloodstream to be carried to the tissues.

5.0Significance of Gluconeogenesis

• Maintain blood glucose levels when carbohydrates are not available in the diet.
• During prolonged starvation, hepatic glycogen storage is totally depleted. So glucose is continuously supplied to the brain, lens, cornea, and kidney medulla. They need a continuous supply of glucose.
• It is used to clear the product of the metabolism of other tissues from the blood.