Glycogen Metabolism

Glycogen Function In liver – The synthesis and breakdown of glycogen is regulated to maintain blood glucose levels. In muscle - The synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell.

Liver Cell

Glycogen structure Large molecule Branch points are frequent (about every fourth residue) – allows glucose residues to be easily added or removed quicker than a linear molecule. Glucose residues linked by α (1-4) glycosidic bonds into chains & chains branch via α (1-6) linkage

Liver glycogen varies with food intake, with a high level after a meal, and decreasing slowly as it is mobilized to maintain blood glucose levels. (see fig).

Glucose-6-phosphatase phosphoglucomutase phosphoglucomutase G-1-phosphate uridylyl transferase Glycogen synthases

Insulin Peptide hormone of 51 aa produced in the pancreas The stimulation of glycogen synthesis is one of the major physiological responses modulated by insulin The exact mechanism by which insulin stimulates glycogen synthesis is not known Insulin: * Controls uptake and transport of glucose

Reciprocal Regulation of Glycogen Synthase and Glycogen Phosphorylase Glycogen Synthesis and Degradation are Highly Regulated Pathways: • Glycogen synthase and glycogen phosphorylase are the regulatory enzymes of glycogen synthesis and degradation. Insulin Induces and activates protein phosphatase-1 (removes p from GS- Activates GS Feeding results in glycogen synthesis Glucagon activates Protein kinase A which phosphorylates and inactivates glycogen synthase and activates GP Little glycogen synthesis during fasting. Lots of breakdown

Effect of Hormone on Glycogen Metabolism low blood glucose > pancreas release glucagon >>>>>>> promotes glycogen degradation During stress > release epinephrine (adrenal medulla) Promotes glucagon release > increase blood glucose interacts directly with both muscle and liver cells to promote glycogen degradation High blood sugar > release insulin (B-cells) >>>>> > glycogen synthesis

Exercise and Glycogen Metabolism Exercise of a muscle triggers mobilization of glycogen to form ATP. The yield of ATP and the fate of carbons from glycogen depends on whether the muscles is “white” or “red”. Red muscles are supplied with rich supply of blood, have a large amount of myoglobin, and are packed with mitochondria.

In “red” muscles glycogen is converted to pyruvate. Then pyruvate is converted to CO2 and H2O + ATP (due to O2 and mitochondria). “White” muscles have a poorer supply of O2 and fewer mitochondria. Glycogen -------> Lactate primarily White muscles have more capacity for glycogenolysis and glycolysis than red muscle fibers.

In Red muscles glycogen provides energy for longsustained activities In Red muscles glycogen provides energy for longsustained activities. ( O2 & mitochondria, more ATP) In White muscles glycogen provides energy for short periods of maximal activity. (glycogen is mobilized rapidly) In humans most skeletal muscles are a mixture of red and white fibers to provide for both rapid and sustained muscle activity.

McArdle's Disease Glycogen phosphorylase deficient cannot break glycogen > glucose There is an abnormal accumulation of glycogen in muscle tissue. Symptoms are exercise intolerance - muscular pain, fatigability - and muscle cramping. Rest relieves the muscle pain and enables exercise to resume

Muscle phosphorylase enzyme histochemistry in a control muscle shows the normal checkerboard staining pattern. Phosphorylase staining was absent in the patient's muscle Assay Normal* (nmol/min/g) Patient Glycogen† 0.1-1.5 1.85 Phosphorylase A 12.00 0.09 Phosphofructokinase 12.8 15.21 Myoadenylate deaminase 15.88 19.13 *

Study Questions What’s the importance of glucose? What is glucose stored as in the body? Where is it stored? How much glycogen can be stored? What’s the significance of glycogen being highly branched? Is there any difference in the functions performed by the liver and muscle glycogen? If so what is it? Define glycogenesis and glycogenolysis? By the aid of diagrams explain the process of glycogenesis and glycogenolysis. 9. Which hormones are involved in regulating these processes - glycogenesis and glycogenolysis? 10. Why is it important that these processes are rigorously controlled? How is blood glucose regulated? What is the energy requirements of the white and red muscles and why is there a difference in energy requirements in these muscles? 13. What is glycogen storage disease and discuss one example (cause and symptoms) of such disease.