Glycogen metabolism - glycogenolysis Flashcards
__________________________ is a polymer of glucose found in the liver and skeletal muscle in large granules in the cytoplasm.
Glycogen
What types of linkages characterize glycogen?
Alpha 1–>4 linkages with alpha 1–>6 linked branches
What are the large granules full of glycogen also called?
Rosettes
What is the metabolic role of glycogen?
Energy storage
Glucose source
What are two problems with using fat stores as fuel?
- Fats cannot be used in anaerobic conditions
- Glucose is sole source of energy for brain
What is the name for the breakdown of glycogen?
Glycogenolysis
Glycogenolysis requires three enzymes. What are they?
- Glycogen phosphorylase (GP)
- Debranching enzyme (transferase, glucosidase)
- Phosphoglucomutase
What is considered to be the main enzyme responsible for glycogen degradation?
Glycogen phosphorylase
How does glycogen phosphorylase operate?
Phosphorolysis
What is the mechanism of glycogen phosphorylase?
- Oxygen on nonreducing end kicks back to form oxonium intermediate
- Alpha 1–>4 linkage broken, releasing glycogen n-1
- Inorganic phosphate attacks former anomeric carbon, forming glucose-1-phosphate
What is important about the fact that glycogen phosphorylase occurs via phosphorolysis?
It saves energy
Glycogen phosphorylase activity continues until it reaches the _____ glucose from the alpha1–>6 branch point, where it stops. This leaves a “_______ _______.”
4th
Limit branch
_________________ ____________ is a bifunctional enzyme that contains two active domains: a transferase and glucosidase.
Debranching enzyme
The _______________ activity of the debranching enzyme moves three glucose units from a branch to a nearby non-reducing end, leaving a single glucose molecule at the branch point.
Transferase
The _________________ activity of the debranching enzyme hydrolyzes the remain single glucose; approximately 10% of glucose is lost this way.
Glucosidase
What enzyme uses a phosphoserine residue to form glucose-1,6-bisphosphate intermediate?
Phosphoglucomutase
What happens to the glucose-6-phosphate produced from glycogen?
In muscle, G6P is shuttled into glycolysis for the production of ATP
In liver, G6P is dephosphorylated via glucose-6-phosphatase to glucose and released into the blood; alternatively, G6P can enter the pentose phosphate pathway
Is the overal pathway of glycogen degradation irreversible?
Yes, it is irreversible and therefore regulated
McArdle’s disease results from a defect in muscle ___________ ____________________.
Glycogen phosphorylase
Cori’s disease results from a defect in ______________ ________________.
Glycogen debranching enzyme
What are the symptoms of McArdle’s disease?
Tire easily
Exercise-induced cramping and pain
Why do patients with McArdle’s disease tire easily and experience exercise intolerance?
Because they have a defect in glycogen phosphorylase, so they are unable to break down glycogen and to provide muscle cells with needed glucose
What are the symptoms of Cori’s disease?
Enlarged liver
Structurally abnormal tissues and organs
Low blood sugar (hypoglycemia)
Why do patients with Cori’s disease have an enlarged liver, abnormally structured tissues and organs, and hypoglycemia?
Because the defect in glycogen debranching enzyme prevents the degradation of glycogen; as such, glycogen builds up in tissues and organs leading to structural abnormalities and hypoglycemia - cells are unable to access stored glucose
What are the treatments for McArdle’s disease and Cori’s disease?
McArdle’s disease - creatine supplementation, which can create ATP, or sugar feeding before exercise
Cori’s disease - frequent feedings
