Glycogen Metabolism Flashcards
What would be present in a patient who cannot mobilize intracellular glucose reserves during exercise?
Muscle damage - creatine and myoglobin in urine, dark urine
Exercise intolerance - no lactate production during ischemic exercise. Shutting off circulation shut off muscle energy supply
Large deposits of carbs - glycogen and hypertrophy in muscles
What are the two major glycogen reservoirs?
- Skeletal muscle for exercise
- Liver for boosting fasting blood sugar
Glucose has chemical and osmotic activity. How is this solved?
Polymerization to glycogen
When are glycogen stores built? When is glycogen mobilized?
Built in fed state when insulin is high.
Liver stores are mobilized during fasting when glucagon is high
What state are muscles not involved in when it comes to carb storage?
The Fasting State
Describe Glycogen Synthesis
- Begins with activated sugar - UDP-glucose
- Glycogenin adds alpha 1,4-linked glucoses to itself
- Glycogen synthase keeps adding more alpha-linked glucoses
- Branching enzyme introduces alpha 1,6 branches and creates nonreducing ends
What does glycogenolysis require? How does it work?
Requires debranching and phosphorylysis
Glycogen phosphorylase releases glucose 1P from alpha 1,4 linked chains
Debranching enzyme breaks alpha 1,6 linkages and moves alpha 1,4 linked branches
Cell needs glucose 6 phosphatase to release glucose
How is glycogen regulated in the fasting state?
Phosphorylation of both enzymes for glycogen breakdown
Glucagon signals in liver glycogen breakdown. PKA activates Glycogen phosphorylase kinase phosphorylates glycogen phosphorylase which releases glucose 1P and inhibits glycogen synthase through phosphorylation
Low energy. High AMP in muscle signals via AMPK
How is glycogen regulated in fed state?
Glycogen phosphorylase is inhibited and glycogen synthase is stimulated by dephosphorylation via Insulin to activate glycogen synthesis
Contrast presentations of glycogen storage diseases in muscle and the liver
Liver and muscle have different forms of glycogen phosphorylase - phosphorylase defects are liver or muscle specific
Liver only had glucose 6 phosphatase so glucose 6 phosphatase deficiency is liver specific
Both perform autophagy - alpha-glucosidase defect affects all tissues
Liver glucose 6-phosphatase deficiency
Type I Glycogen Storage Disorder: Von Gierke
Liver disease
Affects gluconeogenesis - glucose 6 phosphate builds up leading to lactic acidosis, hyperuricemia
Fasting hypoglycemia and enlarged liver because can’t mobilize glycogen
Acid maltase (lysosomal alpha glucosidase) deficiency
Type II Gycogen Storage Disorder - Pompe
Lysosomal Storage Disease
Affects all tissues
Enlarged liver and heart - accumulate lysosomal glycogen
Muscle Glycogen Phosphorylase deficiency
Type V Glycogen Storage Disorder: McArdle
Affects only muscle
Muscle unable to mobilize glycogen
Exercise intolerance: muscle cramps, fatigue, burgundy urine
What happens with decreased blood glucose?
Glucagon released from alpha cells of pancreatic islets
Glucose release from liver - glycogen breakdown and gluconeogenesis
Reduced glucose consumption and increased fatty acid consumption by most tissues
What happens when blood glucose is increased?
Insulin released from Beta cells of pancreatic islets
Increased glucose uptake by liver, adipose tissue, and muscles
Glucose converted to glycogen (liver, muscle) and fat (liver, adipose tissue)
