Gluconeogenesis Definition

Gluconeogenesis

It is a process transforming non-carbohydrate substrates into glucose.

It is the synthesis of new glucose from non carbohydrate precursors providing glucose when dietary intake is lacking or is insufficient. It is also required in the regulation of acid-base balance, synthesis of carbohydrate derived structural constituents.

Gluconeogenesis works in the opposite direction of glycolysis, which creates glucose from pyruvate, lactate, and glucogenic amino acids. It’s also known as Neoglucogenesis. It’s a universal pathway found in humans, animals, plants, fungus, and other living species.

The definition, occurrence site, importance, and steps involved in the gluconeogenesis pathway will be discussed in this article. The substrates that initiate the gluconeogenesis pathway, as well as the gluconeogenesis regulation, are also discussed.

Table of Contents

• Definition of Gluconeogenesis
• Gluconeogenesis Functions
• Pathway of Gluconeogenesis
• Importance of Gluconeogenesis
• Frequently Asked Questions – FAQs

Definition of Gluconeogenesis

Gluconeogenesis (GNG) is the building of novel glucose molecules in the body as compared to glucose, which is split from the prolonged storage molecule glycogen. It primarily occurs in the liver, but it can also occur in minor levels in the small intestine and kidney. Gluconeogenesis is the reversal of glycolysis, which breaks down glucose molecules into their subcomponents.

Since it requires energy, gluconeogenesis is also known as the “Endogenous glucose pathway.” When the small precursor molecules combine, a high-energy product like glucose is produced. Gluconeogenesis is a necessary cycle that produces glucose, which is used to carry out all catabolic activities and support life.

Gluconeogenesis Functions

Human systems create glucose to keep blood sugar levels in check. Because cells use glucose to create the energy component adenosine triphosphate, blood glucose levels must be maintained (ATP). When a person hasn’t eaten in a while, such as during a crisis or starvation, gluconeogenesis takes place.

Since the body does not have enough carbohydrates from the food to break down into glucose during this time, it must depend on other molecules for gluconeogenesis, such as amino acids, lactate, pyruvate, and glycerol. After glucose is produced in the liver by gluconeogenesis, it is released into the blood, where it can be used for energy by cells in other regions of the body.

Since it requires energy input, gluconeogenesis is also known as endogenous glucose production (EGP). Because gluconeogenesis is the reverse of glycolysis, which releases a lot of energy, gluconeogenesis would be predicted to require a lot of energy input. However, because gluconeogenesis happens when the body is already depleted of energy, it needs workarounds to conserve energy.

Gluconeogenesis and glycogenolysis serve the same purpose. However, they are used differently. Glycogenolysis is commonly used during shorter fasting periods, such as when a person’s blood sugar decreases between meals or after a good night’s sleep, but gluconeogenesis is more commonly employed during longer periods of fasting. Both processes, however, occur to some degree in the body because glucose is required for energy production.

Pathway of Gluconeogenesis

1. Gluconeogenesis originates in the liver or kidney’s cytoplasm or mitochondria. To make oxaloacetate, two pyruvate molecules are required to carboxylate first. This requires one ATP (energy) molecule.
2. NADH converts oxaloacetate to malate, which can then be transported out of the mitochondria.
3. Once malate leaves the mitochondria, it is oxidised back to oxaloacetate.
4. The enzyme Phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to phosphoenolpyruvate.
5. By reversing glycolytic processes, phosphoenolpyruvate is converted into fructose 1,6-bisphosphate.
6. Fructose-1, 6-bisphosphate is converted to fructose-6-phosphate in the reaction releasing inorganic phosphate and is catalysed by fructose-1,6-bisphosphatase.
7. The enzyme phosphoglucoisomerase converts fructose-6-phosphate to glucose-6-phosphate.
8. Glucose-6-phosphate generates inorganic phosphate that yields free glucose, which enters the blood. Glucose 6-phosphatase is the enzyme involved.

In the Mitochondria

Pyruvate + ATP → Oxaloacetate + ADP + Pi

Oxaloacetate + NADH → Malate + NAD⁺

The conversion to malate enables the molecule to be transferred out of mitochondria. It is converted back to oxaloacetate in the cytoplasm.

In the Cytoplasm

Malate + NAD⁺ → Oxaloacetate + NADH

Oxaloacetate + GTP → PEP + GDP

It then passes through the same intermediates that glycolysis does. The endoplasmic reticulum is the location of the final reaction.

In the Endoplasmic Reticulum

G6P → glucose (catalyst: glucose-6-phosphatase)

Glucose is transported out of the cell into the extracellular environment by a glucose transporter.

Gluconeogenesis of Amino acids

Importance of Gluconeogenesis

• During deprivation, the gluconeogenesis cycle is important for blood glucose regulation.
• Many cells and tissues, including RBCs, neurons, skeletal muscle, the medulla of the kidney, testes, and embryonic tissue, rely on glucose to meet their energy needs.
• The Neoglucogenesis cycle removes metabolites such as lactate (produced by muscles and RBCs) and glycerol from the bloodstream (produced from adipose tissue).

Related Links:

• Glycogenesis
• What is the main function of gluconeogenesis?
• Is gluconeogenesis glycolysis in reverse?
• What is the difference between glycolysis and gluconeogenesis?