Gluconeogenesis- Steps, Reactions and Significance


Gluconeogenesis is the process of synthesizing glucose from non-carbohydrate sources, such as lactate, pyruvate, glycerol, and certain amino acids. Glucose is the main source of energy for most cells in the body, especially the brain and red blood cells. Gluconeogenesis ensures that the blood glucose level is maintained within a normal range when dietary intake or glycogen stores are insufficient.

Gluconeogenesis is not simply the reversal of glycolysis, which is the breakdown of glucose to pyruvate. Although some of the reactions are the same, there are three irreversible steps in glycolysis that must be bypassed by different enzymes in gluconeogenesis. These steps are:

  • The conversion of glucose to glucose-6-phosphate by hexokinase or glucokinase
  • The conversion of fructose-6-phosphate to fructose-1,6-bisphosphate by phosphofructokinase-1
  • The conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase

The enzymes that catalyze these steps in gluconeogenesis are:

  • Glucose-6-phosphatase, which converts glucose-6-phosphate to glucose
  • Fructose-1,6-bisphosphatase, which converts fructose-1,6-bisphosphate to fructose-6-phosphate
  • Pyruvate carboxylase and phosphoenolpyruvate carboxykinase, which convert pyruvate to phosphoenolpyruvate

Gluconeogenesis is regulated by hormonal and allosteric factors that control the activity of these key enzymes. The main hormones that stimulate gluconeogenesis are glucagon and cortisol, which are secreted during fasting, stress, or low blood glucose levels. The main hormones that inhibit gluconeogenesis are insulin and epinephrine, which are secreted during feeding, exercise, or high blood glucose levels. The allosteric factors include the substrates and products of the reactions, as well as other metabolites that reflect the energy status of the cell.

Gluconeogenesis is an important metabolic pathway that allows the body to maintain a steady supply of glucose for vital functions. It also helps to clear excess lactate and amino acids from the blood and prevent their accumulation. Gluconeogenesis requires energy and reducing equivalents from other sources, such as fatty acids and amino acids. Therefore, it is coordinated with other pathways of carbohydrate, lipid, and protein metabolism.