Gluconeogenesis COURSE TITLE: BIOCHEMISTRY 2 COURSE CODE: BCHT 202 PLACEMENT/YEAR/LEVEL: 2nd Year/Level 4, 2nd Semester M.F.Ullah, Ph.D

Glucose Homeostasis Gluconeogenesis, which occurs primarily in the liver, is the pathway for the synthesis of glucose from compounds other than carbohydrates. In humans, the major precursors of glucose are lactate, glycerol, and amino acids, particularly alanine Glucose homeostasis refers to the maintenance of blood glucose levels under varying states of fed, fasting and starvation. Some tissues of the body, such as the brain and red blood cells, cannot synthesize glucose on their own, yet depend on blood glucose for energy. Therefore, to survive, humans must have mechanisms for maintaining blood glucose levels.

After a meal containing carbohydrates, blood glucose levels rise (fed state).Some of the glucose from the diet is stored in the liver as glycogen. During fasting, this glycogen begins to be degraded by the process of glycogenolysis, and glucose is released into the blood. As glycogen stores decrease, adipose triacylglycerols (TAGs)are also degraded, providing fatty acids as an alternative fuel and glycerol for the synthesis of glucose by gluconeogenesis. Amino acids are also released from the muscle to serve as gluconeogenic precursors. During an overnight fast, blood glucose levels are maintained by both glycogenolysis and gluconeogenesis. However, after approximately 30 hours of fasting (starvation), liver glycogen stores are mostly depleted and gluconeogenesis is the only source of blood glucose.

Changes in the metabolism of glucose that occur during the switch from the fed to the fasting state are regulated by the hormones insulin and glucagon. Insulin is elevated in the fed state, and glucagon is elevated during fasting. When there is excess of glucose in blood after a carbohydrate rich diet, Insulin stimulates the uptake of glucose by the cells and also transport of glucose into certain cells such as those in muscle and adipose tissue and its storage as glycogen in liver. When the blood glucose levels goes down during fasting or starvation, Glucagon stimulates the release of glucose from glycogen by glycogenolysis and the conversion of lactate, amino acids, and glycerol to glucose by gluconeogenesis. Hormones in Glucose Homeostasis

Sources of blood glucose during different nutritional states in order to maintain glucose homeostasis

Since gluconeogenesis is essentially a reversal anabolic pathway of catabolic glycolysis most of the steps of gluconeogenesis use the same enzymes that catalyze the process of glycolysis. The flow of carbon, of course, is in the reverse direction. There are three reaction sequences of gluconeogenesis that differ from the corresponding steps of Glycolysis and use non-glycolytic enzymes: 1.Conversion of pyruvate to phosphoenolpyruvate (PEP) Enzymes: pyruvate carboxylase & PEP carboxykinase 2. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate Enzyme: Fructose bisphosphatase 3.Conversion of glucose 6-phosphate to glucose Enzyme: Glucose 6-phosphatase 3 reactions of gluconeogenesis that are catalyzed by non-glycolytic enzyme

The three major carbon sources for gluconeogenesis in humans are lactate, glycerol, and amino acids, particularly alanine.

During anaerobic glycolysis in cells such as RBCs or muscles (during exercise) glucose is taken up from the blood and metabolized to lactate. This lactate is released in to the blood from where it is taken up by other tissues such as the liver. In liver lactate is converted back to pyruvate which is used to synthesize glucose (by gluconeogenesis), and the glucose is returned to the blood. The cycling of lactate and glucose between peripheral tissues and liver is called the Cori cycle Cori Cycle