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Regulation of Glycogen Metabolism
Enzymes
Glycogen Usage
Glycogen Storage Diseases
Clinical Symptoms
100
What are two hormones that regulate liver glycogen levels but not glycogen levels in skeletal muscle?
Insulin and glucagon.
100
What is the general name of the enzyme responsible for glycogen breakdown?
Glycogen phosphorylase
100
What is the level of ATP demand that makes glycogen an important source of fuel?
High ATP demand.
100
What is the inheritance pattern of McArdle disease?
Autosomal recessive inheritance 65+ mutations exist. Variations of heterozygosity also exist and contribute to differing degrees of disease severity.
100
What is a characteristic finding in a patient with accumulations of glycogen in the liver?
Hepatomegaly or hypoglycemia.
200
What is a quicker response to a need to increase blood glucose, glycogenolysis or gluconeogenesis?
Glycogenolysis responds more quickly.
200
What is the G protein subunit known to be associated with activation of adenylyl cyclase and increased levels of cAMP?
G s
200
What is liver glycogen the immediate source of?
Glucose for maintaining blood glucose levels.
200
What is the enzymatic deficiency that cause McArdle disease and what is the normal function of this enzyme?
McArdle disease is caused by a deficiency of myophosphorylase. This enzyme normally initiates glycogen breakdown by removing 1,4-glucosyl groups from glycogen w/ release of glucose 1-phosphate. Myophosphorylase is present in cardiac muscle & brain and it is only isoform in skeletal muscle
200
What is the cause of the tea-colored urine reported by McArdle's patients?
Myoglobinuria causes the tea-color. Myoglobinuria is usually the result of rhabdomyolysis or muscle destruction. Any process that interferes with the storage or use of energy by muscle cells can lead to myoglobinuria.
300
What is the role of epinephrine in glycogen degradation and synthesis in the liver?
Epinephrine is released in response to a need for increased demand for glucose. In the liver: epinephrine acts on alpha-receptors to stimulate glycogenolysis and inhibit glycogen synthesis by increasing calcium levels in the liver. Epinephrine, acting on beta-receptors, regulates glycogen breakdown and synthesis through G protein cAMP pathway to activate phosphorylation of the involved enzymes.
300
What is the enzyme that allows the liver to convert glucose 6 phosphate directly into glucose? The muscle lacks this enzyme.
Glucose-6 phosphatase
300
What is a benefit of the branched structure of glycogen?
1. increased site for synthesis and degradation 2. increased molecular solubility
300
What is more likely to be fatal: liver glycogen storage disease or muscle glycogen storage disease?
Liver glycogen storage diseases are more likely to be lethal than that of muscle because liver glycogen is first source for blood glucose levels. Deficiency in liver glycogen phosphorylase (or any other enzymes involved in the degradation of liver glycogen) can result in fasting hypoglycemia.
300
What is the cause of the "second wind" phenomenon experienced by patients with McArdle's disease?
Second wind=sudden improved tolerance to aerobic exercise (walking or cycling) after a warm-up. Excessive fatigue disappears and patients continue to exercise. In McArdle's patients “second wind” phenomena is due to the oxidation of fatty acids as additional energy source for these patients. ATP need is increased during exercised and initially dependent upon glucose from glycogen breakdown catalyzed by phosphorylase, this glucose serves as substrate for glycolysis leading to the production ATP via TCA cycle. Once this source has been exhausted, exercising muscle then derives energy from blood sources (glucose & free fatty acids).
400
What is the type of glycogen phosphorylase (muscle or liver) that AMP activates in an allosteric manner? Explain why for an extra turn!
Muscle isozyme of glycogen phosphorylase is activated by AMP. Muscle glycogen phosphorylase contains a purine nucleotide binding site. AMP binding changes the conformational of the enzyme to a structure similar to its phosphorylated, active state.
400
What is the role of hepatic protein-phosphatase-1 in glycogen metabolism in the liver?
Hepatic protein-phosphatase-1 removes phosphate groups from phosphorylase kinase, glycogen phosphorylase and glycogen synthase. Hepatic protein-phosphatase-1 is inactive during fasting.
400
What is the name of the molecule that glycogen is degraded into which is an important component both glycolysis and the pentose phosphatase pathway?
Glucose 6 phosphate.
400
What is reflected by an increase in venous ammonia concentration after the ischemic forearm exercise in a patient with a muscular glycogen storage disease?
Increases in venous ammonia levels relative to a healthy individual reflect the shortage of ATP in the exercising muscle of a patient with a GSD. ATP use is exceeding the resynthesis of ATP in these patients. AMP is converted to IMP by adenylate deaminase in the context of ATP shortage.
400
What is the reason for cardiac failure in young patients with type 2 glycogen storage disease (Pompe Disease), which is characterized by a genetic defect of lysosomal glucosidase?
Lysosomal glucosidase is required for a small percentage of degradation of cellular glycogen. The deficiency of this enzyme leads to the accumulation of structurally normal glycogen in lysosomes and cytoplasm. Excessive accumulation leads to enlargement and dysfunction of the organs with the glycogen accumulation.
500
What is the mechanism by which a decreased insulin:glucagon affects glycogen levels within the level? Go to the board!
Glucagon binding to glucagon receptor in the liver activates adenylate cyclase via G proteins, which synthesizes cAMP from ATP. cAMP binds to & activates PKA (cAMP-dependent protein kinase) PKA activates phosphorylase kinase which phosphorylates specific serine residues on glycogen phosphorylase b converting it to the active glycogen phosphorylase a PKA also phosphorylates glycogen synthase, which inactivates it. These changes in enzyme activation and inhibition lead to the degradation of glycogen to glucose 1-phosphate. Glucose 1-phosphate is converted into glucose 6 phosphate Liver has glucose 6 phosphatase and therefore directly converts G6P to glucose released into blood circulation.
500
What is the name of the enzyme that activates both glycogenolysis and glycolysis? Its role in glycolysis is stimulated by AMP.
Phosphofructokinase-1
500
What is the name of the protein to which the anomeric carbon at the beginning of the glycogen chain is attached?
Glycogenin
500
What is the deficient enzyme in a type of glycogen storage disease that results in the accumulation of glycogen in liver, muscle, heart and other tissues? Hint: accumulated glycogen have abnormal structure
Deficiency of glycogen debrancher enzyme results in glycogen with short outer chains in liver, muscle, and heart tissues. Glycogen phosphorylase cleaves glucosyl residues by adding phosphate to anomeric carbon of terminal glycosidic bond to release G 1-P & produce free 4’hydroxyl group on glucose residue at end of chain. Glycogen phosphorylase can’t act on 4 residues closest to branch pt, the debrancher enzyme catalyzes removal of these residues.
500
What is the reason that a patient with Tarui syndrome (phosphofructokinase-1 deficiency) typically presents with enzymopathic hemolysis?
It's in RBCs!! Phosphofructokinase is found in muscle tissue and red blood cells. A partial deficiency of phosphofructokinase in the red blood cells results in the breakdown of RBCs and an increase in blood levels of bilirubin. Phosphofructokinase catalyzes the rate-limiting step in glycolysis. Its deficiency decreases the rate of conversion of fructose-6-phosphate to fructose-1,6-diphosphate. PFK deficiency can also lead to increased uric acid production and therefore possible gout. There may be a compensated hemolytic anaemia.