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)
How does epinephrine affect carb catabolism and ATP concentration?
Increases muscle ATP production
Liver gluconeogenesis, glycogenolysis, and muscle glycolysis is up
Signaling through cAMP and Ca2+ - adrenergic receptors
How does cortisol affect carb catabolism and ATP concentration?
Want more glucose for long-term stress
Cortisol increases glucose supply
Liver gluconeogenesis and glycogen synthesis is up
Glycolysis occurs as needed
Glucose deposition in adipose tissue is down
Loss of muscle mass, immune function, and hyperglycemia
What are the pathways of Alcohol Metabolism?
- Alcohol dehydrogenase
- Microsomal Ethanol Oxidizing System
- Catalase Peroxisome
How does alcohol dehydrogenase metabolize alcohol?
Alcohol dehydrogenase metabolizes ethanol to acetaldehyde and NADH
Aldehyde dehydrogenase then produce acetate from acetaldehyde and produces NADH
Zero order kinetics
Cytosolic
How does the microsomal ethanol oxidizing system metabolize alcohol?
Consumes NADPH
Induction of cyt p450 at Smooth ER - lowers defenses and increase radical stress
Hydroxyethyl Radical produced
How does Catalase Peroxisome metabolize alcohol?
Catalase activity in peroxisome take ethanol and hydrogen peroxide to produce water
What is the problem list of Ethanol?
Produce NADH - interferes with gluconeogenesis
Consumes NADPH - increase radicals
Acetaldehyde is toxic
Hydroxyethyl is mutagenic
Why is NADH problematic with ethanol metabolism?
Inhibits citric acid cycle - acetyl-CoA directed to fatty acid and ketone body production
Increase risk for fatty liver disease and ketoacidosis
Inhibits gluconeogenesis - reduces pyruvate and oxaloacetate, elevates risk for lactic acidosis
Why is NADP problematic in ethanol metabolism?
Lack of NADPH lower antioxidant defense and increase radical stress
Why is acetaldehyde problematic in ethanol metabolism?
Flushing, hangover
Low activity of aldehyde dehydrogenase causes alcohol intolerance
Why is hydroxyethyl radical and MEOS activity problematic for ethanol metabolism?
Hydroxyethyl radical damages DNA and increases risk for liver cancer
Increased p450 activity changes metabolism of drugs
How does a patient with alcohol use disorder present?
Alcohol impairs liver functions in carb metabolism - fasting hypoglycemia and metabolic acidosis (poor gluconeogenesis and lactate and ketone production). Fatty liver (production and storage of fat)
Liver disease impairs uptake and storage of vitamins of carb metabolism - Wernicke Korsakoff syndrome and beri beri
