L20- Glycogen Metabolism Flashcards
Describe the structure of glycogen.
Glycogen is composed of glucose molecules linked linearly with alpha(1->4) bonds, with branching chains linked alpha(1->6) to the main glucose chain at intervals of approximately eight residues.
In which tissue(s) is glycogen primarily synthesized and stored?
Liver and muscle.
Most of the liver glycogen stores are depleted after how many hours of fasting?
12-18 hours.
For what purpose does the liver break down glycogen?
To maintain blood glucose levels, especially during an episode of fasting.
For what purpose does muscle break down glycogen?
To make ATP for muscle contractions.
What is the reaction carried out by glycogen synthase?
Glycogen synthase attaches the C1 of an activated UDP-glucose to the C4-OH of a terminal glucose on a pre-existing glycogen chain (leads to the formation of a linear polymer of glucose residues).
What protein acts as a primer for glycogen synthesis?
Glycogenin.
Describe the mechanism by which glycogen branching enzyme synthesizes glycogen branches.
Glycogen branching enzyme cleaves off a glycogen fragment of seven glucose units from the terminal end of a linear glycogen chain that is 12-16 units long. The enzyme then re-attaches the fragment through an alpha(1->6) bond to a glucose at least four residues beyond the last branch.
Under what physiologic condition does the liver synthesize glycogen?
Glycogenesis occurs in the liver when blood sugar levels rise above resting levels.
Name the enzyme(s) that carry out glycogen breakdown.
Glycogen phosphorylase and debranching enzyme.
Name the enzyme(s) that carry out glycogen synthesis.
Glycogen synthase and branching enzyme.
Which enzyme cleaves glucose residues one at a time from the end of an alpha(1->4) linked glycogen chain?
Glycogen phosphorylase.
What kind of enzymatic reaction does glycogen phosphorylase catalyze?
Phosphorolysis.
What is the product of the phosphorolytic cleavage of glucose residues by glycogen phosphorylase?
Glucose-1-phosphate.
What are the two activities of debranching enzyme?
Glucan transferase activity and alpha(1->6) glucosidase activity.
What is the reaction carried out by the glucan transferase activity of debranching enzyme?
The glucan transferase activity cleaves a trisaccharide fragment from the end of a 4-residue-long branched chain, and re-attaches that fragment through an alpha(1->4) linkage to the end of a different chain.
What remains attached at the glycogen branch point after action of the glucan transferase activity of debranching enzyme?
A single glucose residue attached to a chain via an alpha(1->6) linkage.
Which enzyme catalyzes the cleavage of alpha(1->6) linkages at glycogen branch points?
The alpha(1->6) glucosidase activity of debranching enzyme.
What kind of enzymatic reaction does the alpha(1->6) glucosidase activity of debranching enzyme catalyze?
Hydrolysis.
What molecule is released from the hydrolytic cleavage of alpha(1->6) linkages by the glucosidase activity of debranching enzyme?
Free glucose.
What enzyme catalyzes the conversion of glucose-6-phosphate to free glucose?
Glucose-6-phosphatase.
What is the major product of glycogenolysis?
Glucose-1-phosphate.
Glycogen metabolism in muscle responds to which hormone(s)?
Epinephrine and insulin (but not glucagon).
Glycogen metabolism in the liver responds to which hormone(s)?
Epinephrine, insulin and glucagon.
True or False. Glycogen phosphorylase is more active when it is not phosphorylated, whereas glycogen synthase is more active when it is phosphorylated.
False. It is the opposite: glycogen phosphorylase is more active when it is phosphorylated, whereas glycogen synthase is more active when it is not phosphorylated.
The binding of glucagon and epinephrine to specific cell surface receptors leads to the cAMP-dependent activation of which enzyme involved in the regulation of glycogen metabolism?
Protein kinase A (also called cAMP-dependent protein kinase).
What is the effect of glucagon on the activity of glycogen synthase and glycogen phosphorylase?
Glucagon decreases the activity of glycogen synthase and increases the activity of glycogen phosphorylase.
What is the effect of insulin on the activity of glycogen synthase and glycogen phosphorylase?
Insulin increases the activity of glycogen synthase and decreases the activity of glycogen phosphorylase.
What is the effect of elevated glucose and fructose-1-phosphate on glycogen synthase and glycogen phosphorylase?
Glucose and fructose-1-phosphate decrease glycogen breakdown by favoring the inactivation of glycogen phosphorylase and the activation of glycogen synthase.
What is the effect of elevated glucose-6-phosphate on glycogen metabolism?
Glucose-6-phosphate stimulates glycogen synthesis.
How does glucose-6-phosphate stimulate glycogen synthesis?
Glucose-6-phosphate inhibits the protein kinase that phosphorylates glycogen synthase. This maintains glycogen synthase in its active form, favoring glycogen synthesis.
How does glycogen limit its own synthesis?
Glycogen accumulation inhibits protein phosphatase. This prevents glycogen synthase from being activated while maintaining glycogen phosphorylase in its active form.
Phosphorylase kinase is activated by calcium. How does this work?
The protein calmodulin binds calcium. Calcium-bound calmodulin then activates the kinase that phosphorylates phosphorylase kinase, thus activating it.
Which glycogen storage disease is characterized by the accumulation of glycogen within lysosomes, particularly in muscle cells?
Type II (Lysosomal acid maltase deficiency, also referred to as Pompe).
Debranching enzyme deficiency results in which glycogen storage disease?
Type III (also referred to as Forbes-Cori).
Which glycogen storage disease is characterized by deposits of abnormal glycogen in the liver, leading to progressive liver cirrhosis and death by the second year?
Type IV (Branching enzyme deficiency, also referred to as Anderson).
Which glycogen storage disease is characterized by muscle cramps during vigorous exercise, lack of lactate after vigorous exercise, and higher amounts of normal-structured glycogen?
Type V (muscle phosphorylase deficiency, also referred to as McArdle).
Which glycogen storage disease is characterized by muscle cramping and exercise intolerance? It is also sometimes associated with hemolytic anemias.
Type VII (muscle phosphofructokinase deficiency, also referred to as Tarui).
Which glycogen storage disease is characterized by hypoglycemia between meals, hyperlipidemia, acidosis, and poor growth?
Type I (Glucose-6-phosphatase deficiency).
