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Transcript
Glycogen metabolism Glycogen is homopolysaccharide formed of branched α-DGLUCOSE units (α1,4and α1,6) each branch is made of 6-12 glucose units , at the branching point the chain is attached by 1-6 link site: present in cytoplasm of liver and muscles.• Function of glycogen : A) liver glycogen: it maintains normal blood glucose concentration in early stage of fasting 12-18hours then is depleted B) muscle glycogen : acts as source of energy within the muscle ,during muscle contraction. Definition* synthesis of glycogen (glycogenesis) It is the formation of glycogen is liver and muscle. Steps: glucose molecules are first activated to uridine diphosphate glucose (UDP-6) then is added to glycogen primer to form glycogen. Glucose UTP UDP-glucose glycogen synthase glycogen UDP-glucose- phosphoglucose mutase G-6-Po4 glycogen primer G-1-PO4 pyrophosphorylase UDP-glucose Formation of glycogen: UDP-glucose reacts with glycogen primer .. glycogen synthase (key enzyme) causing elongation of α1-4 branched up to 11 glucose units UDPG +glycogen primer• Glycogen synthase UDP + elongated glycogen primer Branching enzyme: It transfers part of elongated chain (5-8glucose units) to the next chain forming a new α1-6 glucosidic bond . The new branches are elongated by glycogen synthase and the process is repeated . Glycogenesis Glucosen + UDP-Glucose Preformed glycogen Glucosen+1 + UDP Glycogen with one more glucose 1-4 Glycosyl Linkage UDP-Glysosyl transferase 1-6 Glycosyl linkage Glycogenolysis Provides glucose. 2 steps: Hydrolysis of glycosidic bond by glycogenphosphorylase Debranching enzyme. Glycogen phosphorylase Pi Debranching Enzyme [Glucosyltransferase] Debranching Enzyme H2O [Glucosidase] Glycogen phosphorylase Pi Pi 1-4 Glycosyl linkage I . Breakdown of glycogen (glycogenolsis) Definition : it is a breakdown of glycogen into glucose in liver and lactic acid in muscles. Steps: Phosphorylase (key enzyme): act on α(1-4bond) removes glucose units in the form of glucose-1-P then the branch contains 4glucose unit, 3of them are transferred to the next branch by transferase enzyme leaving the last one. Debranching enzyme: The last glucose units attacked to the original branch by α 1-6 bond is removed by debranching enzyme then glucose-1PO4 are converted of G-6-Po4 by mutase. Then phosphatase give glucose. Fat of glucose-6-Po4 In liver: it is converted to glucose by G-6-phosphotase. In muscle: no G-6-phosphatase – So, glucose-6-PO4 enter glycolysis to give lactate. Regulation of glycogenesis and glycoenolysis Conditions that stimulate glycogenolysis inhibit that of glycogenesis. - During fasting: increase glycogenolysis and decrease glyconeogensis so provid blood glucose. - After meal: glycogensis is stimulated and glycogenolysis is decreased Glycogen storage disease: there are group of inherited disorder cause deposition of abnormal quantity of glycogen in tissues lead to deficiency of glucose-6-phosphatase like. Von-jierk's disease: 1- Accumulation of large amount of glycogen in liver , enlargement of it increase liver enzyme, hepatomegaly, Fasting hypoglycemia, ketosis and hyper lipidemia. Glconeogenesis Definition : Is a formation of glucose from non carbohydrate source they are: 1-lactate 2- pyruvate 3-glycerol 4-some amines acids 5-propinate Function : Supply body with glucose ( RBCs ,S.M) Glucose give milk sugar (lactose) When glycogen is depleted after 18 hours source of glucose It clear the blood from waste product e.g. lactate and glycerol. Location : cytosol and mitochondria of liver and kidney. Organs : liver 90% , kidney 10% Steps: reversal of glycolsis except the Three irreversible kinase which is replaced by the following enzymes : Glukokinase ≠glucose-6-phosphatease Phosphofructo kinase ≠ fructose 1,6biophosphatase Pyruvate kinase ≠ pyruvate carboxylase * Phosphoenol pyruvate carboxy kinase Pyruvate → oxaloacetate → malate (mitochondria) → REP x oxaloacetate (cytoplasm) → phosphoenol pyruvate Pathways for defferent sources of glyconeogenesis: Any substance can join to common pathway of gluconeogenesis is glycogenic 1)lactate is converted to pyruvate: Lactate +NAD Lactate dehydrogenase pyruvate + NAD+H Pyruvate can join common pathway give glucose. 2) From glutamate α-ketoglutarate → malate α-ketoglutarate → succinyl COA → fumarate → malate (go to) → cytoplasm 3) Propionic acid in ruminauts only 4) From glycerol from adipose tissue during fasting 2 molecules of glycerol → glucose Regulation of gluconeogenesis: Hormonal regulation 1. Gucocorticoids, cortisol stimulate: induce synthesis of gluconeogenesis enzymes increase catabolism of protein give amino acids increase process 2. Glucagon: decrease level of fructose-2,6-bisphosphate 3. Insulin: decrease gluconeogenesis decrease the three enzymes 4. Acetyl COA and ATP: increase by decrease glycolysis. Decrease phsphofructokinase and increase gluconeogenesis by increase fructose-1,6-bisphosphatase •Acetyl COA increase pyruvate carboxylase and inhibit pyruvate dehydrogenase Role of insulin in lowering blood glucose level Muscle Glucose uptake Blood glucose Glycogen synthesis Liver Glucose metabolism Glycogen synthesis Glycolysis Gluconeogenesis + + FA synthesis + Pancreas Beta cells TG synthesis Insulin secretion VLDL synthesis + Glucose uptake FA uptake TG synthesis Adipose tissues VLDL Role of Liver in controlling blood glucose level - Insulin not needed for uptake of glucose by liver - Insulin is needed for uptake of glucose by other tissues uptake Liver Glycogen Lactate Amino acid Glycerol Blood glucose Glucose Glucose synthesis (gluconeogenesis) blood glucose Glycogen breakdown to blood glucose Other Tissue s Glucose is metabolised Blood glucose