Regulation via Insulin
Regulation via Glucagon/ Epi
Insulin’s Effect on Glycogen Synthase
AND Phosphorylase
Epi and Glucagon
If both synthesis and degradation occurred simulataneously in a cell there
would be a futile cycle.
Glycogen Synthase and
How is such a futile cycle prevented??
Phosphorylase are reciprocally
regulated
Glycogen Phosphorylase:
• a homodimeric enzyme, subject to allosteric
control.
• It transitions between “relaxed” (active) &
“tense” (inhibited) conformations.
• A glycogen storage site on the surface of the
Phosphorylase enzyme binds the glycogen
particle
“LESS
active”
“MORE
active”
“LESS
active”
“MORE
active”
α- Adrenergic Activity in Liver and Ca++
Epi and Glucagon
Muscle and Liver in Exercise
•
•
•
Liver is taking in lactate converting it to pyruvate, then making glucose via
gluconeogenesis and dumping it into bloodstream
When exercising- that glc is taken up by muscle and used to make more
pyruvate/lactate and cycle continues
When stop exercising- muscle cells stop taking up as much glc- thus liver glc conc
goes up- this serves as signal to decrease glycogen breakdown.
Think about this in terms of exercising muscle and how liver helps out
Liver cells make glucose! Muscle cells do not. Presence of high conc of glc in cell
indicates that blood glucose is adequate= no need to make more glucose.
The cAMP binds to protein kinase A (PKA), a cAMP-dependent protein kinase, activating it. PKA in turn phosphorylates other
downstream target proteins including phosphorylase kinase (PhosK) and glycogen synthase (GS). The phosphorylation of PhosK
leads to its activation. Conversely, phosphorylation of GS causes its inhibition stopping the formation of glycogen. The activated
PhosK then phosphorylates the next kinase in the chain, glycogen phosphorylase kinase (GPhos). Phosphorylation of GPhos
activates the enzyme leading to the release of glucose subunits from glycogen. Thus a chain of phosphorylations leads to the
activation of some downstream signaling components while inhibiting others.
Epi and Glucagon
Hormone (epinephrine or glucagon)
via G Protein (G-GTP)
Adenylate cyclase
(inactive)
Adenylate cyclase
(active)
catalysis
ATP
cyclic AMP + PPi
Activation
Phosphodiesterase
AMP
Protein kinase A
(inactive)
Protein kinase A
(active)
ATP
ADP
Phosphorylase kinase
(b-inactive)
Phosphatase
Phosphorylase kinase (P)
(a-active)
ATP
Pi
ADP
Phosphorylase
(b-allosteric)
Phosphorylase (P)
(a-active)
Phosphatase
Pi
Insulin’s Role in Regulating Glycogen
Synthase