· It is the storage from of glucose in animals Glycogen metabolism ·   It is the storage from of glucose in animals ·   Stored in liver (6-8%) and muscle (1-2%) Helps to maintain the blood glucose levels,between meals Glycogen stores increase in a well-fed state depleted during fasting ·  Muscle glycogen serves as a fuel reserve for the supply of ATP during muscle contraction In homopolysaccharide, glucose molecules held together by - 1,4 linkages. Branch with -1, 6 linkage. Glucokinase in liver and hexokinase in muscle which converts glucose to glucose–6 phosphate DR S Nayak

Synthesis of glycogen from glucose Occurs in liver and muscle Glycogenesis Synthesis of glycogen from glucose Occurs in liver and muscle Storage from in liver and muscle After the meal excess glucose is converted into glycogen UDPG is the carrier of glucose Glucose from UDPG is attached at the non-reducing end of glucose molecules of glycogen primer DR S Nayak

ATP ADP Phosphoglucomutase Glucose Glu –6-P Glu-1-P Hexokinase Glucokinase UDPG pyrophosphorylase UTP PPi Uridine diphosphate glucose (UDPG) Glycogen synthase Glycogen primer UDP Glycogen (1, 4 glucosyl units) n (1, 4 and 1,6 Branching enzyme Glucosyl units) n (Amylo-1, 4-1,6- transglucosidase) (Glucosyl -4,6 transferase) DR S Nayak

Glycogenesis DR S Nayak

a specific protein,GLYCOGENIN can accept glucose   It is found that in the absence of glycogen primer, a specific protein,GLYCOGENIN can accept glucose from UDPG. The initial glucose is attached to the OH group of tyrosine residue of glycogenin. The enzyme glycogen initiator synthase transfers the first molecule of glucose to glycogenin. Later glycogenin itself takes up a few glucose residues to form a fragment of primer Branching enzyme (Amylo 1,4 –1,6 transglucosidase transfers 6 glucose residues portion from one chain to a neighbouring chain to form a -1,6 – linkage DR S Nayak

Breakdown of glycogen to glucose ·Occurs in liver and muscle Glycogenolysis Breakdown of glycogen to glucose ·Occurs in liver and muscle ·End product of liver glycogenolysis is glucose ·Muscle glycogenolysis is lactate (strenuous exercise) Muscle and brain does not contain glu-6-phosphatase Phosphorylase Pi Glycogen Glu-1-P Phosphoglucomutase Glu –6-P Glu-6-Phosphatase H2O Pi Glucose DR S Nayak

Phosphorylase phosphorolytically splits -1,4 glucoside bonds from the outermost chains of glycogen until 4 residues remain on either side of – 1.6 branch point [limit dextrin]   1.4 glucan transferase transfers 3 glucose residue portion from one side chain to the other exposing -1,6 branch points Amylo 1, 6 glucosidase splits the 1,6 linkages Acid maltase or -1,4-glucosidase (lysosomal enzyme) degrades small quantity of glycogen. The significance of this pathway is not clear v                     Muscle glycogenolysis Glycogen  Glu-1-P  Glu-6-P   glycolysis  lactate DR S Nayak

Glycogenolysis DR S Nayak

Regulation of glycogenesis and glycogenolysis ·  The glycogen synthase and phosphorylase exist in active and inactive forms ·  The dephosphorylated form of glycogen synthase is active ·  Phosphorylated form of phosphorylase is active The activation of phosphorylase depends on high cAMP level. At the same time high cAMP level inactivates glycogen synthase Glycogen synthase b Phosphorylase a H2O Protein phosphatase Pi Glycogen synthase a Phosphorylase b (Glycogenesis ON) (Glycogenolysis OFF) DR S Nayak

Allosteric regulation In a well fed state Glu–6– P level is high which activates glycogen synthase ·   On the other hand glu-6-p and ATP allosterically inhibit phosphorylase · Free glucose also act as inhibitor to phosphorylase Glucose –6 –P ATP Liver glucose Muscle AMP _ _ _ Glycogen Phosphorylase + Ca2+ Glycogen Glu-1-Phosphate Glycogen Synthase + Glucose-6-phosphate DR S Nayak

Glucagon + (Liver only) Adenylate Cyclase Adenylate Cyclase ATP cAMP Adrenaline (Liver and muscle) Glucagon + (Liver only) Adenylate Cyclase Adenylate Cyclase ATP cAMP PPi Protein Kinase Protein Kinase ATP ADP ATP ADP Phosphorylase Phosphorylase Glycogen Glycogen Kinase kinase Synthase (a) synthase (b) Phosphorylase (b) Phosphorylase (a) 2ATP 2ADP Glycogen Glucose-1-P Pi cAMP 51 AMP Glycogenesis ON + Phosphodiesterase Insulin DR S Nayak

GLYCOGEN STORAGE DISEASES Genetic diseases [may be inherited] Deposition of abnormal type or quantity of glycogen in the tissues Diseases Defect and Features Type I. Glucose – 6 – phosphatase [liver] Von Gierke’s disease Accumulation of glycogen in liver Hypoglycaemia and ketosis Type II. Lysosomal -1, 4 – glucosidase Pompe’s disease Glycogen accumulates in lysosomes, in all tissues Enlarged liver and heart Type III. Debranching enzyme [amylo -1,6- Limit dextrinosis glucosidase [Coris disease] Accumulation of polysaccharide [limit dextrin] liver, heart, & muscle TypeIV. Amylo pectinosis or Branching enzyme (glucosyl 4-6 transferase) Andersons disease Accumulation of polysaccharide with few branch points. Cirrhosis of liver DR S Nayak

Type V Muscle glycogen phosphorylase McArdles disease Glycogen accumulates in the muscle Diminished tolerance to exercise Type VI. Liver glycogen Phosphorylase Hers disease Liver enlarged Von Gierke’s Disease 1. Fasting hypoglycemia 2. Lactic acidemia:Glucose is not synthesized from lactate produced in muscle and liver. Lactate level increases and pH decreases 3. Hyperlipidemia: Block in gluconeogenesis leads to mobilisation fat to meet energy requirement. So This increases free plasma FA & ketone bodies. 4. Hyperuricemia: Accumulated glucose -6-p diverted to HMP pathway, leading to increased synthesis of ribose and nucleotides, this enhances metabolism of purine nucleotides and to uric acid later 5. Massive liver enlargement leads to cirrhosis 6. Children fail to grow Given small quantity of food at frequent intervals DR S Nayak

DR S Nayak