Glycogen metabolism

Glycogen is homopolysaccharide formed of branched α-D- GLUCOSE 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. glycogen glycogen primer UDP-glucose UTP Glucose glycogen synthase UDP-glucose UDP-glucose- G-1-PO 4 phosphoglucose mutase G-6-Po4 pyrophosphorylase

Formation of glycogen: UDP-glucose reacts with glycogen primer.. glycogen synthase (key enzyme) causing elongation of α1-4 branched up to 11 glucose units UDP + elongated glycogen primer Glycogen synthase UDPG +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 Glucose n UDP-Glucose + Glucose n+1 + UDP Preformed glycogenGlycogen with one more glucose UDP-Glysosyl transferase  1-4 Glycosyl Linkage

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Glycogenolysis  Provides glucose.  2 steps:  Hydrolysis of glycosidic bond by glycogen- phosphorylase  Debranching enzyme. Pi  1-6 Glycosyl linkage  1-4 Glycosyl linkage Glycogen phosphorylase Debranching Enzyme [Glucosyltransferase] Debranching Enzyme [Glucosidase] Glycogen phosphorylase Pi H2OH2O

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-1- PO4 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.

Definition : Is a formation of glucose from non carbohydrate source they are: 1-lactate 2- pyruvate 3-glycerol 4-some amines acids5-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. Glconeogenesis 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 VLDL Insulin secretion Beta cells Pancreas  Blood glucose  Glucose uptake  Glycogen synthesis  Glucose metabolism  Glycogen synthesis  Glycolysis  Gluconeogenesis  FA synthesis  TG synthesis  VLDL synthesis  Glucose uptake  FA uptake  TG synthesis Adipose tissues Muscle Liver

Role of Liver in controlling blood glucose level  Blood glucose  Blood glucose Liver - Insulin not needed for uptake of glucose by liver - Insulin is needed for uptake of glucose by other tissues  uptake Glycogen Glucose Glycogen breakdown to  blood glucose  Glucose synthesis (gluconeogenesis)  blood glucose Lactate Amino acid Glycerol Other Tissue s Glucose is metabolised