Chapter 25 Flashcards
what is UDP-glucose?
(uridine diphosphate glucose)
activated form of glucose
the glucose donor in glycogen synthesis
what synthesizes UDP-glucose?
by UDP-glucose pyrophosphorylase
what renders the synthesis of UDP-glucose irreversible?
the hydrolysis of pyrophosphate
how is UDP-glucose synthesized?
UDP-glycose pyrophosphorylase hydrolyzes UTP and puts it in glucose
what drives the synthesis of UDP-glucose reaction to the right?
the cleavage of PPi
what does glycogen synthase do in the reaction of Glucose to UDP-glucose?
glycogen synthase catalyzes the transfer of glucose from UDP-glucose to a growing chain
what does glycogen synthase do in the synthesis of glycogen?
it transfers a glucose moiety from UDP-glucose to the C-4 terminal residue of a glycogen chain to form an α-1,4-glycosidic bond
what does glycogen synthase require as a primer?
an oligosaccharide of glucose residues
what synthesizes the primer needed by glycogen synthase?
glycogenin
what is glycogenin?
a dimer of two identical subunits
what does each subunit of glycogenin do?
each subunit generates an oligosaccharide of glucose residues 10-20 molecules long
what does glycogen synthase do to the primer?
it extends the primer
glycogen synthase can only synthesize what kind of linkages?
α-1,4-linkages
what does a branching enzyme do?
it generates branches allowing glycogen synthase to extend the branch polymer
how does a branching enzyme create branches?
it generates branches by cleaving an α-1,4-linkage and taking a block of approximately 7 glucoses and synthesizing an α-1,6-linkage,
what does the branching of an enzyme allow?
increase insolubility
increases ends for synthesis and degradation
when is glycogen synthase inactive?
when in the phosphorylated b form
when is glycogen synthase active?
in the unphosphorylated a form
what is the key regulatory process of glycogen synthesis?
the conversion of the b form in the T state to the active R state by binding glucose 6-phosphate
what is the difference between phosphorylation of glycogen synthase and glycogen phosphorylase?
it has opposite effects
glycogen phosphorylase is phosphorylated and active in a form and unphopshorylated in b form
glycogen synthase is phosphorylated in b form and unphosphorylated in a form
Quick quiz: why is the fact that phosphorylation has opposite effects on glycogen synthesis and breakdown advantageous?
what inhibits glycogen synthesis?
- phosphorylation of glycogen synthase by protein kinase A (PKA) to form glycogen synthase b
- phosphorylation by glycogen synthase kinase (GSK)
what does insulin do to glycogen synthesis pathways?
it turns on pathways to store glucose
when levels of glucagon and epinephrine GO UP do you want to turn on synthesis of glycogen or turn it off?
what happens during the FED state?
there is high glucose levels
what happens during the FASTING state?
there are low glucose levels
how does the regulation of protein phosphatase 1 in muscle take place?
- Phosphorylation of Gm by protein kinase A dissociates the catalytic subunit from its substrates in the glycogen particle
- Phosphorylation of the inhibitor subunit by protein kinase A inactivates catalytic unit of PP1
what does protein phosphatase 1 (PP1) do to the glycogen metabolism?
- it shifts glycogen metabolism from the degradation mode to the synthesis mode
- it removes phosphoryl groups from glycogen synthase b, converting it into the more active a form
- it removes phosphoryl groups from the phosphorylase kinase and glycogen phosphorylase, inhibiting glycogen degradation?
how does PP1 inhibit glycogen degredation?
it removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase
how does insulin stimulate glycogen synthesis?
by activating a signal transduction pathway that results in the phosphorylation and inactivation of glycogen synthase kinase
what does PP1 do to glycogen synthase?
is dephosphorylates glycogen synthase, generating the active a form of the synthase, activating it and allowing glycogen synthesis
how does insulin facilitate glycogen synthesis?
by increasing the number of glucose transporters (GLUT4) in the plasma membrane
what does insulin do to glycogen synthase kinase?
insulin triggers a cascade that leads to the phosphorylation and inactivation of glycogen synthase kinase and prevents the phosphorylation of glycogen synthase
what does glycogen metabolism in the liver regulate?
blood-glucose levels
how do high blood-glucose levels effect glycogen degradation and synthesis?
degradation in the liver is inhibited
synthesis is stimulated
what does the binding of glucose to glycogen phosphorylase do?
it converts glycogen phosphorylase a from the R state to the T state
what does the conversion of glycogen phosphorylase a from R to T state by glucose cause?
the activation of PP1 that is associated with the phosphorylase
what does PP1 do to the glycogen metabolism?
it converts the glycogen metabolism from a degradation mode to a synthesis mode
what is the first step in glucose regulation of liver-glycogen metabolism?
glucose binds to glycogen phosphorylase a and inhibits it, facilitating the formation of the T state of phosphorylase a
what does the T state of phosphorylase a cause in the liver?
The T state of phosphorylase a does not bind protein phosphatase 1 (PP1), leading to the dissociation of PP1 from glycogen phosphorylase a, and its activation
what does the free PP1 do to the liver-glycogen metabolism?
it dephosphorylates glycogen phosphorylase a and glycogen synthase b, leading to the inactivation of glycogen breakdown and the activation of glycogen synthesis
how does glucose regulate liver-glycogen metabolism
- glucose binds glycogen phosphorylase, inhibiting it
- inhibition of glycogen phosphorylase causes formation of T state of phosphorylase a
- T state of phosphorylase a does not bind protein phosphatase 1 (PP1)
- PP1 dissociates from glycogen phosphorylase a, activating it
- free PP1 dephosphorylates glycogen phosphorylase a and glycogen synthase b
- glycogen breakdown is inactivated
- glycogen synthesis is activated
what do phosphorylase and synthase activity depend on in the liver?
glucose
as glucose increases, phosphorylase activity….
decreases
as glucose increases, synthase activity….
increases
at low glucose __ is active
phosphorylase
at high glucose, ___ is active
synthase
what is diabetes?
it is characterized by the presence of excess glucose and underutilization of the fuel
where is excess glucose secreted in people with diabetes?
urine
what is type 1 diabetes (T1D)?
childhood onset
insulin is not produced
how is type 1 diabetes managed?
injection of insulin
what is type 2 diabetes (T2D)?
insulin is produced by the insulin-signaling pathway is not responsive, a condition referred to as insulin resistance
how is type 2 diabetes managed?
diet
