1. Glycogen metabolism

2. 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.

4. 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

5. 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.

6. 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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14. 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.

15. 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 FASTING STATE *Decrease blood glucose glycogenolysis is stimulated by - CAMP and Protein kinase - Ca ++ and calmodulin protein ` *Decrease blood glocose → stimulate epinephrine and nor epinephrine and glucagon. *These hormones stimulate adenyl cyclase enzyme which convert ATP → CAMP → stimulate protein kinase which cause phosphorylation to both glycogen synthase and glycogen phosphorrylase. Glycogen synthase phosphorylated glycogen synthase Protein kinase ATP ADP (inactive)

16. Phophorylase phosphorylated phosphorylase Protein kinase ATP ADP (active) As a result glycogenolysis will proceed causing increase of blood glucose at the same time glycogenesis will be inhibited. AFTER MEAL: Increase blood glucose level stimulate insulin. Insulin causes : -stimulate phosphodiestrase enzyme, convert CAMP to AMP so abolish the stimulatory effect of CAMP so stimulation of phosphatase which decrease phosphorylase and increase glycogen synthase so glycogenesis will proceed and decrease glycogenolysis.` Phosphorylated Phosphorylase Phosphorylase Phosphatase pi (inactive)

20. 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. Phosphorylated glycogen synthase glycogen synthase Phosphatase Pi (Active) AMP phosphor diesterase 3,5 CAMP Adenyl Cyclase ATP

21. Difference between liver and muscle glycogen: Muscle glycogenLiver glycogen Blood glucose only1-blood glucose 2-other hexoses (fructose) 3-non carbohydrate source e.g: Lactate Source 350 gram120 gramAmount 1%6%Conc. Private source of energy for muscle only It maintain normal blood glucose conc. Between meals Function Lactate due to absence of glucose-6-po4 in muscle glucoseEnd products Same No effect Stimulate glycogeneses Stimulate glycogenolysis Effect of hormones 1-Insulin 2-Epinephrine 3-Glucagon

22. 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

23. 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

24. 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

25. 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