Glycogen Metabolism Flashcards
Insulin causes glycogen ___
Glucagon causes glycogen __
During prolonged fasting/starvation, the brain can also use __ as a fuel source
Insulin = glycogen synthesis
Glucagon = glycogen breakdown
Prolonged fasting/starvation -> brain can use ketone bodies
Glycogen is synthesized and stored in what two types of tissue? How do they differ in what they do w/ the glycogen?
Both breakdown the glycogen into glucose 1-phosphate then glucose 6-phosphate
THE MUSCLE locks glucose 6-phosphate into the cell to use for glycolysis –> energy
THE LIVER breaks down glucose 6-phosphate with glucose 6-phosphatase in gluconeogenesis –> glucose to release to blood for other cells during fasting
Structure of glycogen
Linear polymer of glucose residues aligned in repeating a-1,4 glycosidic linkages, with periodic branches formed by a-1,6 glycosidic linkages
Steps of glycogen synthesis
- Glucose-6-phosphate –phosphoglucomutase–> Glucose-1-phosphate
- Glucose-1-phosphate + UTP –UDP-glucose pyrophosphorylase -> PPi + UDP-Glucose
- PPi is broken down into two Pi, whcih drives the rxn
-
Glycogen synthase transfers UDP-glucose to glycogen to form a-1,4 linkages
- Glycogen synthase deficiency -> type O glycogen storage disease in hepatocytes -> low BG, high ketone
-
Glycosyl 4,6 transferase creates branches via a-1,6 glycosidic linkages
- Deficiency -> Type IV/Anderson’s glycogen storage disease in skeletl muscle and hepatocytes -> hepatomegaly, splenomegaly, muscle damage, myoglobin in urine
3 benefits of branching
- Increases the # of ends on the molecule for more rapid storage or removal of glucose when needed
- Better for energy storage
- Increases glycogen solubility
Two main enzymes of glycogenolysis
Glycogen phosphorylase: removes single glucose residues by hydrolyzing a-1,4 glycosidic linkages from the ends of linear chains and phosphorylates them –> glucose-1-phosphates
Debranching enzyme has 2 enzymatic activities
- Glucosyl 4,4 transglycosidase transfers residues between branches in a-1,4 glycosidic linkages
- a-1,6 glucosidase hydrolyzes a-1,6-glycosidic linkages, producing glucose
De novo glycogen synthesis
Glycogenin is a “primer” with intrinsic enzymatic activity;
It transfers glucose from UDP-glucose to glycogenin to make short chain of a-1,4-linked residues then glycogen synthase and Branching enzyme picks up where it left off
Process of glycogenolysis
- Glycogen phosphorylase shortens linear chains to 4-residue branches
- Glucosyl 4,4 transglycosidase transfers 3 glucose residues from shroter chains to longer chains (which glycogen phosphorylase will further hydrolyze)
- a-1,6 glucosidase hydrolyzes that single glucose residue’s a-1,6 linkage on that short branch
Deficiency of glycogen phosphorylase causes
Type V/McArdle glycogen storage disease in muscle
Type VI (Hers) glycogen storage disease in liver
Exercise induced muscle cramps and pain, myoglobin in blood, hepatomegaly
Glycogen phosphorylase requries what cofactor?
pyridoxal phosphate (PLP) - the active form of vitamin B6
The major product of glycogen breakdown is Glu
Glucose-1-phosphate (the glucose from debranching is less)
What happens to the glucose-1-phosphates generated from glycogenolysis?
Converted to glucose-6-phosphate by phosphoglucomutase, and enters the glycolytic or gluconeogenic pathways, dpending on whether the tissue is in muscle or liver
Deficiency in the debranching enzyme
type IIIa (Cori of Forbes) glycogen storage disease
Affects liver, skeletal, and cardiac muscle -> infants’ hepatomegaly & generalized myopathy
Liver specific version -> type IIIb glycogen storage disease: infants’ hepatomegaly
Pompe’s disease - enzyme affected, where, and symptoms
Lysosomal acidic a-glucosidase (basically lysosome form of glycogenphosphorylase)
Muscle (skeletal & cardiac)
Lethal within 2 yrs in kids; myopathies in adults
Von Glerke’s disease
Glucose 6-phosphatase
Hepatocytes
Hepatomegaly or Splenomegaly
