Glycogen storage
Glycogenolysis has quick response to which hormones?
glucagon/epinephrine
Where does muscle get energy after glycogen?
fats (130 ATP @C16
How is Cori disease treated?
frequent high carbohydrate meals with cornstarch supplements and a high protein diet
How long does liver glycogen stores usually last while fasting?
16-18 hours
Which muscle type is intermediate?
IIA
Which muscle type has less Mb?
IIB
Which muscle type is fast-twitch?
IIB
Which muscle type is for sprints?
IIB
Which muscle type undergoes anaerobic metabolism?
IIB
How common are glycogen storage diseases?
1 per 20,000-25,000 births in US
How long does muscle glycogen last?
4 hours of heavy exercise
What's the name for Glycogen storage disease type IV?
Andersen Disease; can't branch
How are branches added?
Branching enzyme 4:6 transferase moves 6-8 linkages to make an alpha 1-6 linkage
What's the name for GSD III?
Cori disease
What allosterically inhibits glycogenolysis?
G 6-P, glucose and ATP
What disease results in amylopectinosis?
GSD type 4: Andersen disease
What gene is mutated in GSD 0 muscle?
GYS-1
What gene is mutated in GSD 0 liver?
GYS-2
What's the primary product of gycogenolysis?
Glucose 1-P, which is converted to Glucose 6-P and sent to the ER to become Glucose
What's the first step in adding glucose to glycogen in glycogen synthesis?
Glucose 6-Phsophate becomes Glucose 1-phosphate by Phosphoglucomutase
What's the other name for Glycogen Storage disease type VI?
Hers disease
Which muscle type is for endurance?
I
Which muscle type is slow-twitch?
I
Which muscle type undergoes aerobic metabolism??
I
Why is glycogen the best way to store glucose?
It can be quickly mobilized when needed; can be metabolized anaerobically by glycolysis; can be used to maintain blood glucose homeostasis (liver); doesn't create an osmotic problem for cell as would glucose monomers
What's another name for GSD VII?
McArdles Disease
What enzyme converts G-1P to G-6P?
Phosphoglucomutase
What are the other names for GSD Type II?
Pompe disease or Acid maltase deficiency
What are the genetics of Cori disease?
autosomal recessive; 1:100,000 in general population; 1:5400 North African Jews (1:35 carriers in North African Jews)
How do Epinephrine and Glucagon increase glycogenolysis?
Trimeric Gs protein, adenylate cyclase, clycic AMP, activates protein kinase A, whihc inactivates phosphorylase kinase and activates phosphorylase b to phosphorylase a, which leads to glycogenolysis
What is the third step in adding glucose to glycogen?
UDP comes off and glycogen synthase adds the glucose to the non-reducing end of glycogen via alpha 1-4 linkages
What's the second step in adding glucose to glycogen in glycogen synthesis?
UDP-glucose pyrophosphorylase uses UTP to make UDP-glucose from glucose 1-phosphate
What are the symptoms of GSD 0 in muscle?
begins in early childhood; muscle pain and weakness or episodes of fainting following moderate physical activity; arrhythmias; impairs the heart's ability to effectively pump blood and increase the risk of cardiac arrest and sudden death, particularly after physical activity
How does AMP activate glycogenolysis?
activates glycogen phosphorylase b without phosphorylation by PKA, so under low oxygen/low energy conditions muscle can still undergo glycogenolysis to make ATP
What's the relationship between Glucagon and glycogenolysis?
activates glycogenolysis in liver
What's the relationship between Epinephrine and glycogenolysis?
activates glycogenolysis in muscle
What linkages are formed when a new glucose is added to glycogen?
alpha 1-4 linkage
What are the genetics of McArdles?
autosomal recessive (1/100,000) cihld-onset and adult-onset
What are the genetics for GSD type II pompe disease?
autosomal recessive (1/40,000); gene therapy available (myozyme)
How does insulin activate glycogen synthase?
binds receptor; receptor authophosphorylates; activates IRS (insulin receptor substrate) via phosphorylation of Tyr residues; activates PI-3kinase; phosphorylates PIP2 to PIP3; activates PKB (AKT); phosphorylates and inactivates GSK3; glycogen synthase kinase; PP1 dephosphorylates and activates glycogen synthase
What causes Andersen Disease?
branching enzyme deficiency
What causes Glycogen storage disease type IV?
branching enzyme deficiency
How is muscle glycogenolysis stimulated?
by Ca2+, AMP and Epinephrine
What allosterically activates glycogenolysis in the muscle?
calcium and AMP (activates muscle phosphorylase b and calcium binds calmodulin)
How does Calcium allosterically activate glycogenolysis?
calcium binds calmodulin subunit of phosphorylase kinase which leads to activation of phosphorylase kinase without phosphorylation by PKA
What does glycogen phosphorylase do?
cleaves alpha 1-4 linkages using Pi from non-reducing ends until it reaches 4 glucose units from a branch point
What are the symptoms?
cramps upon exercise; no rise in blood lactic acid after exercise; myoglobinemia and myoglobinuria
Where in the cell does gycogen synthesis occur?
cytosol
Where does glycogenolysis occur?
cytosolic
What causes Cori deases GSD III?
debranching enzyme deficiency; can't debranch
What is amylopectinosis?
decrease in amylopectin-branched glycogen
When is glycogen synthase inhibited?
during fasting state; dephosphorylzation caused by high glucagon levels
When is glycogen synthase activated?
during well fed state; allosterically by Glucose 6-P; phosphorylation caused by high insulin levels
What are the symptoms of GSD type 4: andersen disease?
failure to thrive; heptaosplenomegaly, progressive cirrhosis, muscle hypotonia; death by 5 years of age
What's the most important enzyme in glycogenolysis?
glycogen phosphorylase
What causes Glycogen storage disease type 0?
glycogen synthase deficiency
How is synthesis of a new molecule of glycogen made?
glycogenin adds glucose to a tyrosine in the glycogenin (glycogenin stays in the glycogen polymer)
What are the symptoms of cori disease?
hepatomegaly, fasting hypogycemia, myopathy
What does amylopectinosis cause?
insolubility in glycogen
How is liver glycogenolysis regulated?
insulin/glucagon; blood glucose; epinephrine
What does Glycogen synthase a or I mean?
it's active and dephosphorylated
What does glycogen synthase b or D mean?
it's inactive and phosphorylated
What causes Hers disease?
liver phosphorylase deficiency (usually only partial: complete is fatal)
What organs are effected by GSD Type II Pompe disease?
liver, muscle and heart
Where is the largest single storage site of glycogen, what is its purpose and how much is stored?
liver; used for blood glucose homeostasis; 10 g ~10% of fresh weight liver
What do the glycogen molecules of Andersen's disease look like?
long unbranched molecules
What causes GSD Type II Pompe disease?
lysosomal acid alpha-1,4-glucosidase deficiency (GAA) so you can't degrate lysosomal glycogen and it accumulates;
Where is the largest storage site of glycogen?
muscle; 500 g; 80% of glycogen stores; ~1-2% of fresh weight resting muscle
What are the symptoms of pompe disease? (GSD type II)
normal blood glucose, normal glycogen, muscle weakness, cardiomegaly
What is glycogen phosphorylase's coenzyme?
pyridoxal phosphate (Vit B6) needed at active site
Is UTP a pyrimidine or purine?
pyrimidine
What does the debrancher glucosidase do?
removes the single glucose left at branch site of alpha 1-6
What do the glycogen molecules of Cori's disease look like?
short stumpy branches
What are the symptoms of GSD 0 in liver?
shows in infancy; hypoglycemia after fasting; ketosis; better upon feeding
What causes McArdles Disease?
skeletal muscle phosphorylase deficiency (myophosphorylase)
What is amylopectin?
soluble branched starch found in plants
What is amylose?
straight chain starch found in plants that's less soluble
What does the debrancher 4:4 transferase do?
transfers 3 glucose units to another branch so they're all alpha 1-4 linkages;
What's the usual genetics of glycogen storage diseases?
usually autosomal recessive, some are x-linked