Glycogen Metabolism I Flashcards
Why is glucose stored as glycogen?
it minimizes osmotic stress on the cell
Why use glycogen for storage in addition to fat?
muscle cannot metabolize fat as rapidly, fat cannot be metabolized in anaerobic conditions, and fat metabolism alone is not adequate to maintain blood glucose levels
muscle glycogen
provides quick energy for aerobic or anaerobic metabolism; depleted in less than an hour
liver glycogen
reservoir for glucose for other tissues, critical for brain glucose, depleted in 12-24 hours
glucose-6-P in muscle cells (from glycogen)
will enter glycolysis pathway
glucose-6-P in liver cells (from glycogen)
will be dephosphorylated and released into blood
glycogen structure
alpha-1,4 linkage with alpha-1,6 branches
Which end of glycogen is glucose added and released?
non-reducing end (OH free at C4)
glycogenin
primer for glycogen synthesis by catalyzing the polymerization of the first few glucose molecules
glycosome
granules containing both glycogen and enzymes for synthesizing and degrading glycogen
glycogen phosphoryase
releases glucose-1-phosphate from glycogen
pyridoxal phosphate (vitamin B6)
cofactor for glycogen phosphorylase; acts as general acid catalyst
debranching enzyme
cleaves alpha-1,6 O-glycosidic bonds
glucose-6-phosphatase
dephosphorylates glucose-6-P for release from liver; located in ER lumen
hyperphosphorylated glycogen
degraded by alpha-glucosidase in lysosome
phosphoglucomutase
converts glucose-6-P –> glucose-1-P
UDP-glucose pyrophosphorylase
converts glucose-1-P –> UDP-glucose
first step in glycogen synthesis
transfer of glucose from UDP-glucose to hydroxyl group of Tyr194 on glycogenin (glucotransferase activity)
glycogen synthase
transfers glucose from UDP-glucose to non-reducing end of glycogen chain to extend the chain
glycogen synthase catalyzes
alpha-1,4 linkages
glycogen-branching enzyme
forms alpha-1,6 branches
hepatomegaly
accumulation of normal or abnormal glycogen in liver
fasting hypoglycemia
defect in glycogen degradation or secretion of glucose from liver
glycogen storage disease I (Von Gierke’s)
mutation in glucose-6-phosphatase (1a) or glucose-6-P transporter (1b) which prevents glucose-6-P –> glucose
symptoms of Von Gierke’s Disease
affects liver and kidney; severe hypoglycemia between meals, lethargy, seizures, lactic acidosis, liver and kidney enlargement
Von Gierke’s treatment
frequent small meals infused with cornstarch to act as slow release of glucose; avoid sucrose, lactose, fructose, and galactose
glycogen storage disease II (Pompe’s Disease)
mutation in acid alpha-glucosidase/acid maltose (enzyme in lysosome)
Pompe’s Disease symptoms
affects muscle; glycogen accumulates in lysosomes, enlarged muscles (large tongue), hypotonia, liver enlargement from heart failure, no hypoglycemia (liver still breaks down glycogen), death in childhood
Pompe’s Disease treatment
enzyme replacement therapy
glycogen storage disease III (Cori Disease)
mutation in debranching enzyme
Cori Disease symptoms
affects liver and muscle; similar symptoms of Von Gierke’s except has gluconeogenesis and gycogen accumulates both in liver and muscle; abnormal glycogen with short outer chains
Cori disease treatment
cornstarch in diet, decrease carbohydrates, increase protein
alpha-1,6-glucosidase
debranching enzyme
glycogen storage disease IV (Anderson’s)
mutation in branching enzyme
Anderson’s disease symptoms
affects liver and muscle; hepatomegaly, cirrhosis, liver failure, myopathy, dilated cardiomyopathy, and abnormal glycogen with long unbranched outer chains
Anderson’s disease treatment
liver transplant
glycogen storage disease V (McArdle’s)
mutation in glycogen phosphorylase (muscle isozyme)
McArdle’s Disease symptoms
affects muscle; glycogen not broken down in muscle cells, no liver problems, exercise intolerance, poor endurance, myoglobinuria, creatine kinase release, brown urine after exercise
McArdle’s Disease treatments
avoid intense exercise, vitamin B6 and creatine supplements, and ACE inhibitors
glycogen storage disease VI (Hers Disease)
mutation in glycogen phosphorylase (liver isozyme)
Hers Disease symptoms
affects liver; hypoglycemia, hepatomegaly, lactic acidosis, hyperlipidemia, short stature
Hers Disease treatment
avoid prolonged fasting
glycogen storage disease 0
glycogen synthase deficiency
glycogen synthase deficiency symptoms
affects liver and muscle; morning fatigue (improved with food), postprandial hyperglycemia (glucose not removed from blood since glycogen not made), and fasting hypoglycemia with ketosis
glycogen synthase deficiency treatment
protein rich meals, avoid fasting
