Glycogen Metabolism and Gluconeogenesis PDF

Foundational Sciences PHA810 Glycogen metabolism and gluconeogenesis Goal: To explain glycogen metabolism and gluconeogenesis Objectives: 1. Explain glycogenesis and glycogenolysis 2. Explain gluconeogenesis 3. Explain how the processes are regulated 4. Apply knowledge to real-world or clinical sce...

Foundational Sciences PHA810 Glycogen metabolism and gluconeogenesis Goal: To explain glycogen metabolism and gluconeogenesis Objectives: 1. Explain glycogenesis and glycogenolysis 2. Explain gluconeogenesis 3. Explain how the processes are regulated 4. Apply knowledge to real-world or clinical scenarios. Keywords: glycogenesis, glycogenolysis, gluconeogenesis Reading: Essential Cell Bio, Alberts, Chp 13 and 14 or any biochemistry book I. Glycogenesis A. Glycogen is the storage form of glucose 1. Polysaccharide 2. Stored in liver and muscle a. Stores are limited; once stores are maximized, no more glucose can be stored as glycogen B. Glucose → glucose-6-phosphate (hexokinase/glucokinase) B. Glucose-6-phosphate → glucose-1-phosphate → uridine diphosphate glucose → glycogen C. Glycogen synthase is rate limiting enzyme II. Glycogenolysis A. Glycogen → glucose-1-phophate (glycogen phosphorylase) B. Glucose-1-phosphate → glucose-6-phosphate C. In liver: Glucose-6-phosphate → glucose (glucose-6-phosphatase) 1. Glucose then released into the blood for use by other tissues (primarily the brain) D. In skeletal muscle: no phosphatase enzyme so glucose-6-phosphate cannot leave cell, therefore glucose-6-phosphate enters glycolytic pathway  1. The muscle cell breaks down glycogen to use for itself III. Gluconeogenesis A. Glucose is formed from non-carbohydrate sources 1. Certain amino acids 2. Lactate 3. Glycerol 4. Krebs Cycle intermediates (such as oxaloacetate OAA) B. Gluconeogenesis occurs in the liver and kidneys C. Lactate and certain amino acids can be converted into pyruvate, which is then converted into glucose via “reverse” glycolysis D. Glycerol can be converted into glyceraldehydes-3-phosphate, which then can be converted into glucose via “reverse” glycolysis IV. Regulation of the carbohydrate metabolism pathway  A. Regulation of glycogenolysis 1. Rate limiting enzyme: a. Glycogen phosphorylase 2. (+) AMP, glucagon (stimulates glycogenolysis in the liver, but not in muscle), epinephrine 3. (-) ATP, insulin B. Regulation of glycogenesis 1. Rate limiting enzyme: a. Glycogen synthase 2. (+) insulin 3. (-) glucagon, epi C. Regulation of gluconeogenesis 1. (+) glucagon 2. (-) insulin Note: Insulin is not required for the brain to take up glucose and use it for energy. Also, glucagon does not inhibit glycolysis in the brain. Therefore, in times of high concentration of glucagon and low concentration of insulin (such as during a state of starvation) the brain is able to take up and utilize the glucose that is being dumped out into the blood by the liver via gluconeogenesis and glycogenolysis.