Glycogen synthesis, breakdown and glycogen storage diseases. Flashcards
This molecule represents the comitted step of glycogenesis:
Glucose-1-phosphate
Which enzyme catalyzes the first few glycosydic bonds between glucose molecules during glycogenesis ?
Glycogenin
What kind of bonds does glycogen synthase make :
a (1–>4) glycosidic bonds
What is the role of branching enzyme ?
Branching enzyme : cuts the a(1->4) glycosidic bonds and makes a (1->6) bonds during the synthesis of glycogen from glucose-1-phosphate.
Also called 4,6 transferase because it transferers the glycosidic bond from the 4th to the 6th position.
Regarding glycogenolysis, which enzyme cuts a (1->4) glycosidic bonds until 4 glucosyl units remain on each chain before the branching point ?
Glycogen phosphorylase
Glycogen phosphorylase uses what as a coenzyme ?
Vitamin B6 (pyridoxal phosphate)
What is the molecule produced as a result of the action of glycogen phosphorylase ?
Limit dextrin
What is the main enzyme of glycogenolysis that releases glucose-1-phopshate in great amount ?
Glycogen phosphorylase
Breaks (1–>4) , Makes (1–>4) then breaks (1–>6) releasing free glucose during glycogenolysis :
Debranching enzyme
Glucose-1-phosphate can be converted back to glucose-6-phosphate by phosphoglucomutase and then to glucose by glucose-6-phosphatase. What tissue lacks glucose-6-phosphatase, preventing it from contributing to blood glucose levels ?
Muscles
Glucose-6-phosphatase can only be found in the liver & kidneys.
Glycogenolysis and gluconeogenesis pathway share this common enzyme:
Glucose-6-phosphatase
When there is no external source of glucose (food) what mechanism comes in first to prevent hypoglycemia ?
Glycogenolysis
Gluconeogenesis is a more efficient process to maintain blood glucose in cases of starvation, but the process is longer to kick in.
Regulators of glycogen metabolism in the liver :
Insulin/Glucagon
Epinephrine
Hypoglycemia
Regulators of glycogen metabolism in the muscle :
Epinephrine
High AMP ; Low ATP
Ca2+
Anytime the muscle contracts, Ca2+ is released.
Glucagon & Epinephrine effects :
Activation of glycogen phosphorylase via GPCR signaling pathway using cAMP and protein kinase A as intermediate.
Note that protein kinase A phosphorylates specific serine & threonine residues.
Effects of insulin on glycogen metabolism :
Activates glycogen synthase using phosphoprotein phosphatase as an intermediate.
Stimulates phosphodiesterase which converts cAMP to 5’AMP which antagonizes the effects induced by glucagon/epi.
Glycogen storage diseases resulting from deficiency in glucose-6-phosphatase ?
Von Gierke’s disease
Without this enzyme, there is no release of free glucose from liver cells.
Typical presentation of pts affected with Von Gierke’s disease ?
Severe hypoglycemia
Hepatomegaly
Hyperuricemia
Hyperlipidemia
Lactic acidosis
Usually by 6 months of age, when baby’s meals start to be more spaced out.
Treatment of von Gierke’s disease ?
Avoid fasting
Small frequent meals
Avoidance of fructose and lactose (not readily available sources of glucose).
Pompe’s disease refers to deficiency in what enzyme ?
Lysosomal 1,4 glucosidase (acid maltase)
What is the presentation and consequences of Juvenile onset of Pompe’s disease ?
Glycogen accumulation in lysosomes causes cardiomegaly and hypotonia. Usually, pt dies by age 2 years old.
Condition that results from lack of debranching enzyme where bx shows limit dextrin ?
Cori’s disease (aka Forbe’s)
Liver & muscle debranching enzyme deficiency.
Glycogen storage disease that results in abnormal glycogen structure ?
Cori’s disease
Glycogen storage disease that results in severe hypoglycemia?
Von Gierke’s
Gluconeogenesis is affected.
