Gluconeogenesis pathway enzymes

Gluconeogenesis is the metabolic process by which organisms produce glucose from non-carbohydrate precursors, such as lactate, glycerol, and glucogenic amino acids (StatPearls, 2023). This pathway is primarily active in the liver and, to a lesser extent, the kidneys during periods of fasting or intense exercise to maintain blood glucose levels (NIH, 2022). The pathway is governed by four key rate-limiting enzymes: Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase (PEPCK), Fructose-1,6-bisphosphatase (FBPase), and Glucose-6-phosphatase (G6Pase) (UniProt, 2024). Dysregulation of these enzymes, particularly their over-activation, is a hallmark of type 2 diabetes mellitus, leading to excessive hepatic glucose production and fasting hyperglycemia (PubMed, 2021). Consequently, these enzymes are significant therapeutic targets for anti-diabetic drug development. While metformin is the most well-known drug that indirectly suppresses this pathway, specific inhibitors for FBPase and G6Pase have been explored in clinical trials to improve glycemic control (Journal of Biological Chemistry, 2020). However, therapeutic challenges include the risk of hypoglycemia and potential metabolic side effects like lactic acidosis or hepatic lipid accumulation (Nature Reviews Drug Discovery, 2019).

Other names

Gluconeogenic enzymesGNG pathway enzymesHepatic gluconeogenesis enzymes

Inhibition of key rate-limiting enzymes such as Fructose-1,6-bisphosphatase (FBPase) or Glucose-6-phosphatase (G6Pase) to reduce the liver's production of glucose from non-carbohydrate sources.