Glycogen 2 Flashcards
How is Glycogen synthase allosterically regulated?
Liver: G6P activates
Muscle:
- G6P activates
- Ca2+ inhibits glycogen synthesis by signaling a need for energy - glycogenolysis
Explain the allosteric regulation of glycogen phosphorylase
Liver:
- G6P inhibits
- ATP inhibits
- Glucose inhibits
Muscle:
- G6P inhibits, ATP inhibits
- Calcium and AMP activate
Explain hormonal regulation of Glycogen synthase/synthetase
Inhibited by:
- glucagon/epinephrine
- Protein kinase A
- Protein kinase C
- Calmodulin-dependent kinase
Activated by:
-Insulin/phosphoprotein phosphatase
Explain hormonal regulation Glycogen phosphorylase
Inhibited by:
-protein phosphatase/insulin
Activated by:
- Glucagon/epinephrine
- Protein kinase A
- Calmodulin
- Phosphorylase kinase
How do epinephrine and glucagon affect glycogen synthesis?
Epinephrine (liver and muscle) and glucagon (muscle) switch off glycogen synthesis via cAMP mediated cascade
- they act on cell surfaces to activate Adenylyl cyclase
- cAMP activates protein kinases
- kinases catalyze the transfer of phosphoryl groups between ATP and other molecules, proteins in this case
How can glycogen synthase be activated by protein kinases?
Regulation of glycogen synthase by covalent modification. Phosphorylation converts glycogen synthase from its active alpha form to its inactive beta form
Explain how insulin activated glycogen synthase
- Stimulating phosphodiesterase activity which removes cAMP stimulation
- activating phosphoprotein phosphatase which Dephosphorylates inactive glycogen synthase and makes it active
How does glucose 6-phosphate affect glycogen?
Glycogen synthase-b dependence on glucose 6-phosphate , mechanism for storing glucose when over abundance is signaled by build up of glucose 6-phosphate
What is the effect of glucagon on glycogenolysis/glycogen degradation?
The binding of glucagon to its receptors (liver) or the binding of the epinephrine to B-adrenergic receptors (liver and muscle) stimulates glycogen degradation via protein kinase A
Describe the general regulation of glycogen phosphorylase/ regulation of glycogenolysis
- Active form “a”, phosphorylated
- inactive form “b”, dephosphorylated
- contains binding sites for substrates (glycogen, Pi)
- co-factor (pyridoxal phosphate)
- allosteric activator -cAMP
- allosteric inhibitors- ATP, Glucose, glucose 6-phosphate
What is the role of AMP in muscle?
In muscle, under extreme conditions of anoxia and depletion of ATP,AMP activates glycogen phosphorylase b without it being phosphorylated
What is the role of Calcium in muscle?
During muscle contraction, Ca2+ is released in sarcoplasmic reticulum.
Ca2+ binds to the calmodulin subunit of phosphorylase kinase, activating it without phosphorylation. Phosphorylase kinase can then activate glycogen phosphorylase, causing glycogen degradation
How does epinephrine prevent insulin activity?
The binding of epinephrine to a1-adrenergic receptors stimulates protein kinase C
This inactivated insulin receptors in the liver
Explain in detail, the effect of calmodulin on Ca2+ activity
- Ca2+ is released from the endoplasmic reticulum in response to hormones or neurotransmitters binding to cell-surface receptors
- The transient increase in the intracellular Ca2+ concentration favors the form of the calmodulin-Ca2+ complex
- The calmodulin-Ca2+ complex is an essential component of many Ca2+ dependent enzymes
What is Type VI: HERS disease ?
Type VI: HERS disease
Liver glycogen phosphorylase deficiency
- High glycogen content in liver
- Hepatomegaly
- mild fasting hypoglycemia
- growth retardation
- hyperlipidemia and ketosis
- improvement with age, generally resolved at puberty