Chapter 14: Glycogen, Gluconeogenesis, and the HMP Shunt Flashcards
What is glycogen?
a branched polymer of glucose and represents a storage form of glucose
What organs do glycogen synthesis and degradation primarily take place?
in the liver and sk. muscle
Compare and contrast how glycogen is stored in sk. muscle vs liver.
glycogen is stored in cytoplasm as single granules (sk muscle)
In cytoplasm as clusters of granules (liver)
What is glycogenin?
a central protein core with polyglucose chains radiating outward to form a sphere
Name a benefit of the branches of glycogen?
more glucose is at the periphery of the glycogen molecule so there is faster release of glucose into the blood on demand
What is the rate limiting enzyme of glycogen synthesis?
glycogen synthase
Draw out the steps in glycogen metabolism.
Anabolic then catabolic
Refer to diagram (pg 206)
Glycogen synthase in particular forms which bonds of the glycogen molecule?
α1,4 glycosidic bonds found in the linear glucose chains
What is the hormone that regulates glycogen synthase in the liver?
insulin
What is the hormone that regulates glycogen synthase in the skeletal muscle?
insulin
What are some factors that inhibit glycogen synthase in the liver?
glucagon and epinephrine
What are some factors that inhibit glycogen synthase in the skeletal muscle?
epinephrine
What is another name for the branching enzyme in glycogen synthesis?
glycosyl α 1,4: α 1,6 transferase
What is the purpose of branching enzyme?
to introduce α1,6-linked branches into the granule as it grows
How does branching enzyme work?
- glycogen synthase makes a linear α1,4 linked polyglucose chain
- branching enzyme hydrolyzes an α1,4 bond
- transfers the oligoglucose unit and attaches it with an α1,6 bond to create a branch
- glycogen synthase extends both branches
What is the rate limiting enzyme of glycogenolysis?
glycogen phosphorylase
Contrast hydrolase and phosphorylase.
in contrast to hydrolase, a phosphorylase breaks bonds using Pi rather than H2O
What is the function of glycogen phosphorylase?
breaks α1,4 glycosidic bonds releasing glucose 1-phosphate from the periphery of the granule
What is glycogen phosphorylase activated by in the liver?
epinephrine, glucagon
What is glycogen phosphorylase activated by in sk. muscle?
- epinephrine
- AMP
- Ca2+ (through calmodulin)
What is glycogen phosphorylase inhibited by in the liver?
insulin
What is glycogen phosphorylase inhibited by in sk muscle?
insulin and ATP
What are the steps in how debranching enzyme works?
- glycogen phosphorylase releases glucose 1-P from the periphery of the granule until encounters the first branch points.
- debranching enzymes hydrolyzes the α1,4 bond nearest
- transfers the oligoglucose unit to the end of another chain, then
- hydrolyzes the α1,6 bond releasing the single glucose from the former branch
What is another name for debranching enzyme?
glucosyl α1,4: α 1,4 transferase and α 1,6 glucosidase
Another name for Type I glycogen storage disease?
von Gierke
Another name for Type II glycogen storage disease?
Pompe
Another name for Type III glycogen storage disease?
Cori
Another name for Type IV glycogen storage disease?
Anderson
Another name for Type V glycogen storage disease?
McArdle
Another name for Type VI glycogen storage disease?
Hers
What is the deficient enzyme in von Gierke disease?
Glucose-6-phosphatase
What is the deficient enzyme in Type II glycogen storage disease?
lysosomal α1,4 glucosidase
What is the deficient enzyme in Cori disease?
glycogen debranching enzyme
What is the deficient enzyme in Type IV glycogen storage disease?
branching enzyme
What is the deficient enzyme in McArdles diseases?
muscle glycogen phophorylase
What is the deficient enzyme in Type VI glycogen storage disease?
hepatic glycogen phophorylase
What are the cardinal clinical features of Type I glycogen storage disease?
severe hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, hyperuicemia, short stature, doll-like facies, protruding abdomen, emaciated extremities
What are the cardinal clinical features of Pompe disease?
cardiomegaly, muscle weakness, death by 2 years
What are the cardinal clinical features of Type III glycogen storage disease?
mild hypoglycemia, liver enlargement
What are the cardinal clinical features of Andersons disease?
infantile hypotonia, cirrhosis, death by 2 years
What are the cardinal clinical features of Type V glycogen storage disease?
muscle cramps and weakness on exercise, myoglobinuria (red urine with no RBCs)
“2nd wind phenomenon”
What are the cardinal clinical features of Hers disease?
mild fasting hypoglycemia, hepatomegaly, cirrhosis
Glycogen structure in von Gierke disease?
normal
Describe the glycogen structure in Pompe disease?
glycogen-like material in inclusion bodies
Describe the glycogen structure in Cori disease?
short outer branches, single glucose residue at outer branch
Describe the glycogen structure in Andersons disease.
very few branches, especially toward periphery
Describe the glycogen stucture in McArdle disease?
normal
Describe the glycogen structure in Hers disease?
normal
How does ingestion of galactose or fructose affect blood glucose in one with glucose-6-phosphatase deficiency?
causes no increase in blood glucose because glucose cant be released from cells
How does administration of glucagon or epinephrine affect one with glucose-6-phosphatase deficiency?
has no effect
Why is hyperuricemia associated with Type I glycogen storage disease?
G6P accumulates typing up phosphate in the liver and there is less inorganic phosphate available
Pi -> purine nucleoside accumulation > degraded into purines -> uric acid
uric acid can’t be excreted properly because of the lactic acidosis; hence hyperuricemia and gout
Explain the hyperlipidemia associated with Type 1 GSD?
occurs secondary to hypoglycemia
triglycerides mobilize FA and pour into the blood stream
FA have to go somewhere and go to skin and liver hence skin xanthomas and fatty liver respectively
