Chapter 24 Flashcards
what is the structure of glycogen?
highly branched homopolymer of glucose
nonreducing ends of the glycogen molecule form the surface of the glycogen granule
the protein glycogenin is at the core
why is glucose a more versatile energy source than fatty acids?
where are the largest stores of glycogen found?
the liver and skeletal muscles
where is glycogen found?
in all tissues
what does the liver do to glycogen?
the liver breaks down glycogen and releases glucose to the blood
why does the liver release glucose to the blood?
to provide energy for the brain and red blood cells during nocturnal fasts
what happens to muscle glycogen stores?
muscle glycogen stores are mobilized to provide energy for muscle contraction
why does glucose glycogen cleaved in the muscle stay in the muscle?
where does glycogen degradation take place on the molecule?
at the surface
what does the protein glycogenin do?
it is a primer that begins glycogen degredation
what does glycogen phosphorylase do?
degrades glycogen from the nonreducing ends of the glycogen molecule and catalyzes a phosphorolysis reaction to create glucose 1-phosphate
what does glycogen phosphorylase cleave?
α-1,4-glycosidic bonds
what does transferase do?
shifts a small oligosaccharide near the branch point to a nearby chain
what is the purpose of the transferase moving the oligosaccharide near the branch point?
to make the glucose moieties accessible to the phosphorylase
what does α-1,6 glucosidase do?
cleaves the α-1,6 linkage at the branch point and releases a free glucose
is the reaction of glycogen to glucose favorable or unfavorable?
favorable
what does phosphoglucomutase do?
converts glucose 1-phosphate into glucose 6-phosphate
what happens when the free glucose is phosphorylated by hexokinase?
it produces glucose 6-phosphate
what does phosphoglucomutase do?
it forms glucose 6-phosphate from glucose 1-phosphate
what does phosphoglucomutase use to form glucose 6-phosphate?
glucose 1,6-bisphosphate intermediate
What does glucose 6-phosphatase do in the liver?
it generates free glucose
what happens to the free glucose created from the Calvin cycle?
the free glucose is released into the blood for use by other tissues such as the brain and red blod cells
what is the liver’s role in the body’s glucose levels?
to maintain a nearly constant concentration of glucose in the blood
what is the default state of liver phosphorylase?
The α form in the R state
___ is a negative regulator of liver phosphorylase
Glucose
how does glucose regulate liver phosphorylase?
by facilitating the transition from the R state to the T state
what kind of enzymes are liver phosphorylase and muscle phosphorylase?
isozymes
when is phosphorylase inactive?
when blood glucose is high
what happens to phosphorylase in the T state?
the active site is partly blocked by a regulatory structure
what happens to phosphorylase in the R state?
the active site is unobstructed
what is the default form of phosphorylase in the muscle?
the b form in the T state (unphosphorylated)
what is the predominant form of phosphorylase in the liver?
the a form in R state (phosphorylated)
what doesn’t contribute to regulation of phosphorylase a in the liver?
AMP, ATP, and glucose 6-phosphate
what inhibits phosphorylase a and how?
glucose; it pushes it into the T state
what happens to phosphorylase b when energy is needed in the muscle?
the phosphorylase binds AMP, which stabilizes the R state
what signals to phosphorylase b that energy is needed in the muscle?
an increase in the concentration of AMP
what stabilizes the T state of phosphorylase in the muscle?
ATP and glucose 6-phosphate
what does increasing energy demands do to phosphorylase?
it activates signal transduction pathways to phosphorylate b to a
what are the characteristics of phosphorylase a?
phosphorylated
usually active
R state
predominates in the liver
what are the characteristics of phosphorylase b?
not phosphorylated
usually inactive
T state
predominates in the muscle
what are the characteristics of liver glycogen phosphorylase?
default state is a allosterically regulated by glucose doesn't use much ATP insensitive to AMP R state
what does the allosteric regulation of liver glycogen phosphorylase by glucose do?
binding of glucose to phosphorylase causes shift from R to T state
why is muscle glycogen phosphorylase insensitive to glucose?
muscle uses glucose especially during exercise
what promotes the conversion of phosphorylase b to phosphorylase a?
phosphorylation
what is the difference between the two forms of phosphorylase?
b form is less active
a form is more active and has a phosphorylated serine residue 14
what stimulates phosphorylation of phosphorylase?
the hormones glucagon and epinephrine
what does phosphorylation do to phosphoryalase?
it alters the active site such that alpha helices that partially block the active site in the b form are removed
how is phosphorylase kinase activated in the muscle?
by phosphorylation and calcium ion binding
what is phosphorylase kinase responsible for?
it is the enzyme responsible for the conversion of glycogen phosphorylation from the unphosphorylated b state to the a state
what phosphorylates phosphorylase kinase?
protein kinase A
what is the delta subunit of phosphorylase?
the calcium sensor calmodulin
when is phosphorylase kinase maximally active?
when phosphorylated and bound to calcium
what are type I muscle fibers?
slow twitch fibers
rely primarily on cellular respiration as a means of generating ATP
what are type IIb muscle fibers?
fast twitch fibers
rely primarily on lactic acid fermentation for ATP generation
rich in glycogen phosphorylase
what are type IIa muscle fibers?
have biochemical characteristics intermediates between the other fiber types
what muscle fiber type does glycogen not play a role in?
Type I
is the slow twitch highly dependent on glycolysis?
NO
what causes hers disease?
a deficiency in the liver isozyme of glycogen phosphorylase
what happens to a person suffering from Hers disease?
glycogen accumulates in the liver (hepatomegaly) and hypoglycemia results
what causes both manifestations in Hers disease?
an inability to mobilize glycogen
what initiates Glycogen breakdown?
G proteins transmit the signal for initiation of glycogen breakdown
how does the initiation of glycogen breakdown begin?
glucagon (in liver) and epinephrine (in muscle) initiate G-protein cascades that result in production of cAMP (the Beta-adrenergic receptor)
in the initiation of glycogen breakdown, what initiates the activation of phosphorylase kinase in the muscle?
calcium, released in muscle to stimulate contraction
in the initiation of glycogen breakdown in the liver, how is Ca2+ released?
Ca2+ release is stimulated by epinephrine binding to the α-adrenergic receptor
in the initiation of glycogen breakdown in the liver, what happens after calcium is released?
it activates a G-protein and instigates the phosphoinositide cascade
what does cyclic AMP do in the initiation of glycogen breakdown?
cyclic AMP activates protein kinase A
what does protein kinase A do in the initiation of glycogen breakdown?
it phosphorylates and completes activation of phosphorylase kinase
what does phosphorylase kinase do in the initiation of glycogen breakdown?
it converts glycogen phosphorylase b to the a form, activating glycogen degradation
what are the general steps in the initiation of glycogen breakdown in the muscle?
- epinephrine (muscle) initiate G-proteins
- G-protein cascades result in cAMP
- calcium, released to stimulate contraction, initiates activation of phosphorylase kinase
- cAMP activates protein kinase A
- protein kinase A phosphorylates and completes activation of phosphorylase kinase
- phosphorylase kinase converts glycogen phosphorylase b to a
- glycogen degradation is activated
what are the general steps in the initiation of glycogen breakdown in the liver?
- glucagon (muscle) initiates G-proteins
- G-protein cascades result in cAMP
- epinephrine binds to the alpha0adrenergic receptor and stimulates release of Ca2+
- calcium release activates G-protein and instigates phosphoinositide cascade
- cAMP activates protein kinase A
- protein kinase A phosphorylates and completes activation of phosphorylase kinase
- phosphorylase kinase converts glycogen phosphorylase b to a
- glycogen degradation is activated
what are the mechanisms that shut down glycogen breakdown?
as hormone levels decrease
- the inherent GTPase activity of the G protein renders these proteins inactive
- phosphodiesterase converts cAMP into AMP, which does not stimulate protein kinase A
- Protein phosphatase 1 (PP1) removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, inactivating the enzymes
what happens to G proteins during shut down of glycogen degredation?
inherent GTPase activity of G proteins renders the proteins inactive
how does the stimulation of protein kinase A stop during shut down of glycogen degredation?
phosphodiesterase converts cAMP into AMP, which doesn’t stimulate protein kinase A
