Gluconeogenesis: Definition, Path, Reactions, and Importance of Gluconeogenesis

Definition of Gluconeogenesis

Gluconeogenesis quite literally translates as ‘the production of new glucose’. It is a metabolic pathway that leads to the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids.

It occurs mainly in the liver, though it can also occur in smaller quantities in the kidney and small intestine. Gluconeogenesis is the opposite procedure of glycolysis, which is the breakdown of glucose molecules into their components.

The function of this system, localized in both the cytosol and mitochondria, is to maintain blood glucose level continuously throughout the fasting state. Several tissues, including the brain, erythrocytes, kidney medulla, the lens and cornea of the eye, testes, skeletal muscles during workout, require constant glucose supply.

Among these tissues, the brain utilizes glucose specifically in both the fed state and the fasting state except for prolonged fasting, which uses ketones. Especially, the day-to-day quantity of glucose utilized by the brain represents 70% of the overall glucose produced by the liver in a normal fasting individual.

Initially, throughout the very first hours of fasting, hepatic glycogenolysis is the primary source of glucose. After several hours of starvation, gluconeogenesis and glycogenolysis contribute equally to blood glucose. The amount of glucose supplied by glycogen reduces quickly while the increase in the glucose fraction contributed by gluconeogenesis results in keeping continuous the total amount of glucose produced.

Path of Gluconeogenesis

1. Gluconeogenesis starts in either the mitochondria or cytoplasm of the liver or kidney. First, two pyruvate particles are carboxylated to form oxaloacetate. One ATP (energy) particle is required for this.
2. Oxaloacetate is minimized to malate by NADH so that it can be transferred out of the mitochondria.
3. Malate is oxidized back to oxaloacetate once it runs out of the mitochondria.
4. Oxaloacetate forms phosphoenolpyruvate utilizing the enzyme PEPCK.
5. Phosphoenolpyruvate is altered to fructose-1,6- biphosphate, and then to fructose-6-phosphate. ATP is likewise utilized throughout this procedure, which is basically glycolysis in reverse.
6. Fructose-6-phosphate becomes glucose-6-phosphate with the enzyme phosphoglucoisomerase.

Glucose is formed from glucose-6-phosphate in the cell’s endoplasmic reticulum through the enzyme glucose-6-phosphatase. To form glucose, a phosphate group is eliminated, and glucose-6-phosphate and ATP end up being glucose and ADP.

Reactions of Gluconeogenesis

Conversion of pyruvate to phosphoenolpyruvate

In the liver, pyruvate is transformed to phosphoenolpyruvate.

Pyruvate (produced from lactate, alanine, and other amino acids) is first transformed to oxaloacetate by pyruvate carboxylase, a mitochondrial enzyme that needs biotin and ATP. Oxaloacetate can not directly cross the inner mitochondrial membrane. Therefore, it is transformed to malate or to aspartate, which can cross the mitochondrial membrane and be reconverted to oxaloacetate in the cytosol.

Oxaloacetate is decarboxylated by phosphoenolpyruvate carboxykinase to form phosphoenolpyruvate. This reaction requires GTP. Phosphoenolpyruvate is converted to fructose 1,6-bisphosphate by the turnaround of the glycolytic reactions.

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

Fructose-1, 6-bisphosphate is transformed to fructose-6-phosphate in a reaction that releases inorganic phosphate and is catalyzed by fructose-1,6- bisphosphates. Fructose-6-phosphate is converted to glucose 6- phosphate by the exact same isomerase used in glycolysis.

Conversion of glucose-6-phosphate to glucose

Glucose-6-phosphate releases inorganic phosphate, which produces free glucose that enters the blood. The enzyme involved is glucose 6-phosphatase.

Hence, the net requirements to make one glucose molecule are:

• Two pyruvates.
• Four ATP and 2 GTP.
• Two NADH.
• 6 H₂O

Importance of Gluconeogenesis

Gluconeogenesis fulfills the requirements of the body for glucose when sufficient carb is not available from the diet or glycogen reserves.

Glycogen kept in adipose tissue and in skeletal muscle is converted to glucose by glycogenolysis. However, the stored glycogen might not be sufficient during heavy exercise, diabetic conditions, or during fasting, etc. So during scarcity, glucose is manufactured by the gluconeogenesis process.

A continuous supply of glucose is required as a source of energy, especially for the nervous system and erythrocytes.

The Gluconeogenesis system is used to clear the products of the metabolism of other tissues from the blood, e.g., Lactate, produced by muscle and erythrocytes and glycerol, which is constantly produced by adipose tissue.

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