Glycogen Synthesis Flashcards
What 3 molecules are yielded when glycogen is broken down in the gut? What is the glucose yield of those molecules? What breaks them down?
Maltose (2 glucose), Maltotriose (3 glucose), alpha-dextrin (several glucose that were connected by a 1,6 linkage.
Maltose and Maltotriose are broken down by Maltase, and alpha-dextrin is broken down by alpha-dextrinase
What enzymes are involved in glycogen breakdown in the liver? What is their function?
Glucose phosphorylase phosphorylates the 1,4 linkage of glucose, breaking each monomer off one by one as G-1-P, starting at the non-reducing end.
alpha-(1,6)-glucosidase breaks down the (1,6) linkage at the branch points of glycogen
What is the mechanism behind breakdown of the branch points in glycogen?
Glycogen phosphorylase breaks glucose off of the chain until there are 4 glucose left until the branch point. A transferase transfers 3 glucose from the branch onto the main chain, then alpha-(1,6)-glucosidase cleaves the final glucose off of the branch, yielding the final free glucose of the branch.
What is the product of glycogen breakdown in the liver and by what process is it exported elsewhere?
Glucose-1-Phosphate is the product. It is converted to glucose-6-phosphate by phosphoglucomutase, then converted to Glucose by G-6-phosphatase. It is then exported out of the liver into the body.
Why is G-6-P not able to be transported out of the muscle?
Muscle lacks G-6-phosphatase, and phosphorylated molecules cannot pass the cell wall due to their charge.
Describe the hormone pathway that regulates the breakdown of glycogen. (Glycogen Phosphorylase)
Epinephrine/Glucagon bind to receptors on the cell membrane activating the cAMP pathway, which activates a protein kinase. The PK activates a phosphorylase kinase, which goes on to activate glycogen phosphorylase, which is also stimulated by AMP (low energy levels)
Glycogen phosphorylase is also down regulated by dephosphorylation, which is signaled by insulin. ATP (high energy levels) and high levels of glucose-6-phosphate also inhibit.
Describe and define the purpose of Glucagon
Glucagon is a hormone synthesized by Alpha Pancreatic cells that are released in response to low blood glucose levels. Glucagon begins a signal cascade leading to the breakdown in glycogen. This takes place primarily in the liver, which has many glucagon receptors. The hormone in the muscle that accomplishes this is epinephrine.
What is the process of Glycogen synthesis?
G-1-P reacts with UTP -> UDP-Glucose. The protein Glycogenin initiates synthesis, and the enzyme glycogen synthase begins piecing together each UDP-Glucose into a lengthening glycogen chain. Branching enzyme transfers a 7 glucose chain to another glucose in the chain, creating a branch point.
What are the methods of regulation of glycogen synthesis? (Glycogen Synthase)
Glycogen Synthase is activated by dephosphorylation from protein phosphatase (stimulated by Insulin). Insulin also signals for increased gene expression of GS. High levels of G-6-P also upregulate GS.
Phosphorylation by protein kinases activated in the cAMP cycle inhibit GS. (Remember that the cAMP pathway is initiated by Glucagon)
How is glycogen breakdown signaled in the muscle?
Calcium influx during muscle contraction activates calmodulin, which cascades to activate glucose phosphorylase, stimulating the breakdown of glycogen for glucose in the muscle.
What is the deficiency and clinical symptoms of von Gierke Disease (type 1)
Glucose-6-Phosphatase deficient; glycogen accumulation in the liver and renal tubule cells, hyperglycemia, lactic acidemia, ketosis, hyperlipemia (25% of incidence)
Pompe Disease?
Lysosomal (1,4) and (1,6) glucosidase deficient; accumulation of glycogen in the lysosomes. Juvenile onset -> hypotonia (floppy), death from heart failure by age 2; Adult onset -> muscular dystrophy
Cori Disease (Type III)?
Debranching enzyme deficient; fasting hypoglycemia, hepatomegaly, accumulation of branched glycogen molecules, muscle weakness (23% of incidence)
Andersen Disease (Type IV)
Branching enzyme deficient; hepatosphenomegaly, accumulation of nonbranching glycogen chains, death from heart or liver failure by age 5
McArdle syndrome (Type V)
Muscle Phosphorylase deficient; poor exercise tolerance, blood lactate low after exercise, high muscle glycogen
