Gluconeogenesis: Definition, Steps, Reactions, & Significance

Gluconeogenesis Definition

  • However, glucose must be produced when the cell is utilizing the other carbon molecules. This process is called gluconeogenesis.
  • The process of making glucose from non-sugar precursors is known as gluconeogenesis.
  • The process of synthesizing glucose from substances that are not carbohydrates is known as gluconeogenesis, and it mostly takes place in the liver.
  • When a cell is growing on glucose and receives glucose for polysaccharide synthesis, there is no problem.
  • Phosphoenolpyruvate, one of the intermediate products of the glycolysis pathway, serves as the starting point for glucose synthesis, which proceeds backward along the glycolytic route to create glucose.
  • However, it requires a number of enzymatic processes that do not take place during glycolysis; as a result, glucose is not produced by a straightforward inversion of glycolysis alone.
  • Lactate, amino acids (which produce pyruvate or TCA cycle intermediates), and glycerol are the three main precursors for gluconeogenesis (which forms DHAP).
  • Energy equal to around 6 moles of ATP is needed to synthesize 1 mole of glucose from 2 moles of lactate.
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Location of Gluconeogenesis

  • Gluconeogenesis occurs mostly in the liver, kidney, and gut. 
  • the skeletal muscle is not affected.
  • The initial reaction—catalyzed by pyruvate carboxylase—occurs in the mitochondria.
  • The remaining processes occur in the cytoplasm.

Steps in Gluconeogenesis

  • In the mitochondrion, pyruvate is converted to oxaloacetate by the enzyme pyruvate carboxylase.
  • Malate, or aspartate, enters the cytosol and is then converted back to oxaloacetate.
  • Oxaloacetate is changed into phosphoenolpyruvate by the enzyme phosphoenolpyruvate carboxykinase.
  • Phosphoenolpyruvate reverses the processes of glycolysis to produce fructose 1,6-bisphosphate.
  • When glucose-6-phosphate is required, fructose 1,6-bisphosphatase transforms fructose 1,6-bisphosphate to fructose-6-phosphate.
  • As free glucose is released into the circulation, glucose-6-phosphatase transforms glucose-6-phosphate.
Image Credit: Cambridge University Press

Reactions involved in Gluconeogenesis

1. Conversion of Pyruvate to Phosphoenolpyruvate

  • Phosphoenolpyruvate is created in the liver from pyruvate.
  • Pyruvate carboxylase, a mitochondrial enzyme that needs biotin and ATP, first transforms pyruvate (made from lactate, alanine, and other amino acids) into oxaloacetate.
  • The inner mitochondrial membrane cannot be directly crossed by oxaloacetate. Since it may penetrate the mitochondrial membrane and be converted back to oxaloacetate in the cytosol, it is transformed into malate or aspartate.
  • Phosphoenolpyruvate carboxykinase decarboxylates oxaloacetate to produce phosphoenolpyruvate. GTP is needed for this reaction.
  • By switching the glycolytic processes around, phosphoenolpyruvate is transformed into fructose 1,6-bisphosphate.

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

  • It is a process that produces inorganic phosphate and is mediated by fructose-1,6-bisphosphatase.
  • The fructose-1,6-bisphosphate is converted into fructose-6-phosphate.
  • The enzyme isomerase that is involved in glycolysis converts fructose-6-phosphate to glucose-6-phosphate.

3. Conversion of Glucose-6-phosphate to Glucose

  • Inorganic phosphate is released by glucose-6-phosphate, resulting in the creation of free glucose that enters the circulation. This particular enzyme is glucose 6-phosphatase.

Thus, the following molecules are needed to create one glucose molecule:

  • Two pyruvate.
  • Four ATP and two GTP.
  • Two NADH.
  • Six H2O

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Significance of Gluconeogenesis Pathway

  • Gluconeogenesis fills the void when food or stored glycogen does not provide the body with enough carbohydrates.
  • The process of glycogenolysis produces glucose from the glycogen that is stored in skeletal muscle and adipose tissue. However, in conditions like intense exercise, diabetes, or fasting, the amount of stored glycogen may not be enough. In these circumstances, the gluconeogenesis process produces glucose to fill the gap.
  • A steady supply of glucose is required as a source of energy for the neurological system and erythrocytes in particular.
  • The method of gluconeogenesis is employed to remove the by-products from the blood, such as lactate generated by muscle, erythrocytes, and glycerol constantly created by adipose tissue.

Associated Disease

Hypoglycemia results from a deficiency in any of the gluconeogenic enzymes. It can be deadly if gluconeogenesis fails.


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