Gluconeogenesis - Podcast Version 0:00 / 0:00 1x 0.25x 0.5x 0.75x 1x 1.25x 1.5x 1.75x 2x Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol and glucogenic amino acids. This article will discuss the process of gluconeogenesis as well as relevant clinical conditions. Pro Feature - 3D Model You've Discovered a Pro Feature Access our 3D Model Library Explore, cut, dissect, annotate and manipulate our 3D models to visualise anatomy in a dynamic, interactive way. Learn More Overview of Gluconeogenesis Dwong527 (https://commons.wikimedia.org/wiki/File:Glycolytic_and_gluconeogenic_pathways.jpg), CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0), via Wikimedia Commons Fig 1Diagram showing a summary of gluconeogenesis and glycolysis Process of Gluconeogenesis Gluconeogenesis occurs after around 8 hours of fasting when liver glycogen stores start to deplete and an alternative source of glucose is required. It occurs mainly in the liver and to a lesser extent in the cortex of the kidney. There are three main precursors: Lactate from anaerobic glycolysis in exercising muscle and red blood cells via the Cori cycle Glycerol released from the breakdown of triglycerides in adipose tissue Amino acids (mainly alanine). C Muessig (https://commons.wikimedia.org/wiki/File:The_Cori_cycle.png), CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0), via Wikimedia Commons Fig 2Diagram of the Cori cycle, showing how lactate is generated by muscles and then used by gluconeogenesis Gluconeogenesis has a close relationship to glycolysis. Whilst glycolysis is the breaking of glucose, gluconeogenesis is the creation of glucose. However, it is not simply the reverse of glycolysis, as there are irreversible steps in glycolysis. To circumvent this, some more enzymes are important in gluconeogenesis: Phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to phosphoenolpyruvate. Fructose 1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose 6-phosphate. Glucose-6-phosphatase converts glucose 6-phosphate into glucose. Hormonal Control Like glycolysis, this process is under the tight control of hormones to regulate blood glucose. Stress hormones such as glucagon or cortisol upregulate PEPCK and fructose 1,6-bisphosphatase in order to stimulate gluconeogenesis. However, in a fed, high-energy state gluconeogenesis decreases by inhibiting PEPCK and fructose 1,6-bisphosphatase. Clinical Relevance Diabetes Mellitus Gluconeogenesis is one the major contributors to the hyperglycaemia seen in diabetic patients as cells ‘feel’ starved of nutrients and so send out hormonal signals to increase glucose levels in the blood via gluconeogenesis. Clinical Relevance Alcohol-Related Hypoglycaemia Alcohol abuse alters the NAD+/NADH ratio, leading to excess NADH. This inhibits fatty acid oxidation that provides ATP and favours the pyruvate-to-lactate reaction, depleting the supply of pyruvate for gluconeogenesis and causing hypoglycaemia. This leads to hepatic glycogen depletion combined with alcohol-mediated inhibition of gluconeogenesis and is common in malnourished alcohol abusers. Do you think you’re ready? Take the quiz below Pro Feature - Quiz Gluconeogenesis Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePhysiology Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Frequent questions What is gluconeogenesis? Gluconeogenesis is a metabolic pathway that generates glucose from non-carbohydrate sources such as lactate, glycerol, and glucogenic amino acids. It primarily occurs in the liver and, to a lesser extent, in the kidneys, especially after fasting when glycogen stores are low. What are the main precursors for gluconeogenesis? The primary precursors for gluconeogenesis include lactate from anaerobic glycolysis, glycerol from triglyceride breakdown, and glucogenic amino acids, particularly alanine. These substrates are crucial for maintaining glucose levels during fasting or intense exercise. How does gluconeogenesis relate to glycolysis? Gluconeogenesis is closely related to glycolysis, as it involves the synthesis of glucose, while glycolysis breaks it down. However, gluconeogenesis is not simply the reverse of glycolysis due to specific irreversible steps that require unique enzymes. What hormones regulate gluconeogenesis? Hormones such as glucagon and cortisol play a significant role in regulating gluconeogenesis by upregulating key enzymes like PEPCK and fructose 1,6-bisphosphatase during fasting states. Conversely, these hormones are inhibited in a fed state to decrease gluconeogenesis. How is gluconeogenesis relevant in diabetes mellitus? In diabetes mellitus, gluconeogenesis significantly contributes to hyperglycaemia, as the body perceives a lack of nutrients and signals for increased glucose production. This leads to elevated blood glucose levels, exacerbating the condition in diabetic patients. Rate This Article