Lecture 23: Glycogen Metabolism II Flashcards
(63 cards)
What are the rate limiting enzymes of synthesis and degradation?
synthesis: glycogen synthase
degradation: glycogen phosphorylase
What are the two forms of glycogen synthase?
active non phosphorylated ‘a’ form
inactive phosphorylated ‘b’ form
What is the most important kinase that phosphorylates glycogen synthase?
glycogen synthase kinase (GSK)
What is GSK under the control of?
insulin and PKA
What are the two forms of glycogen phosphorylase?
active ‘a’ form (R relaxed state)
inactive ‘b’ form (T tense state)
Where is the active a form found?
in liver
Where is the inactive b form found?
in muscle
What is glycogen phosphorylase regulated by?
several allosteric effectors
reversible phosphorylation
mutation in liver glycogen phosphorylase causes ____
Hers disease
mutation in muscle glycogen phosphorylase causes ____
McArdle syndrome
Describe allosteric regulation of liver glycogen phosphorylase
in default active a form
made inactive by glucose
glucose bind to active site and stabilizes confirmation in the inactive T state
this is because when glucose levels are high, there is no need to breakdown glycogen
describe allosteric regulation of muscle glycogen phosphorylase
in default inactive b form
activated by AMP
binds to active site and stabilizes conformation of b in the active R state
during muscle contraction ATP converted to AMP by myosin and adenylate kinase signaling the GP to breakdown glycogen
What are negative allosteric regulators of muscle glycogen phosphorylase
ATP and gluc-6-phosphate
glycogenesis is favored in ____ state
fed
What is the fed state?
blood glucose high
insulin high
cellular ATP high
glycogenolysis is favored in the ____ state ( and during ____)
fasting; exercise
what is the fasting state?
blood glucose low
glucagon high
What is high during exercise?
cellular calcium
AMP
What do beta cells release in the pancreas?
insulin
what are the four key proteins involved in regulation by insulin
GLUT 4
protein kinase B (PKB)
protein phosphatase 1 (PP1)
glycogen synthase kinase 3 (GSK3)
What is the net result of insulin regulation?
glycogen synthesis via activation of glycogen synthase and inactivation of glycogen phosphorylase
What causes type 2 diabetes?
reduced sensitivity to insulin ( insulin resistance)
usually caused by mutations in insulin receptor and/or downstream signaling proteins
What is considered normal blood glucose?
70-100 mg/dL (fasting)
< or = to 140 mg/dL (fed)
What is considered prediabetic/at risk blood glucose?
100-125 mg/dL (fasting)
> 140 mg/dL (fed)
