2 glycogen metabolism
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GG LYCOGENLYCOGEN
METABOLISMMETABOLISM
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R OLE OF GLYCOGENR OLE OF GLYCOGEN
Excess dietary glucose isstored as glycogen .Excellent short-term storage
material that can provide
energy immediately.
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GLYCOGEN STO R ESGLYCOGEN STO R ES
M ain stores of glycogen arein:
y M uscley Liver
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ST RU CT UR E OFST RU CT UR E OF
GLYCOGENGLYCOGEN
M ost are joined by an a-1,4
linkage, to make straightchains.
An a-1,6 linkage occurs every8 to 12 glucose residues, tomake branch points.
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R OLES OF LIVE R ANDR OLES OF LIVE R AND
M U SCLE GLYCOGENM U SCLE GLYCOGEN
LIVERGLYCOGEN
MUSCLE GLYCOGEN
Mainfunction
Maintenance of blood glucose
Fuel reserve for musclecontraction
Other roles Used as a fuel byany tissue
Cannot leave muscle
Size of stores Lasts only about12-24 hours
during a fast
Approximately 1-2%weight of muscle
Hormonalcontrol
Glucagon and Adrenalinepromotesglycogenbreakdown
Adrenaline promotesglycogen breakdown
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GLYCOGENESISGLYCOGENESIS
takes place in cell cytosolthree enzymes:
y uridine diphosphate (UDP)y glucose pyrophosphorylasey glycogen synthaseb ranching enzyme
y amvlo (1,4 -> 1,6)transglycosylase
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GLYCOGENESISGLYCOGENESIS
Glycogen synthesisit starts with the formation of
UDP-glucose, which then takes partin the elongation of the glycogenmolecule.When the growing glycogen chain islong enough, a polysaccharide of between five to eight units isbroken off and transferred to aneighboring chain to form a branchchain.
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TT H R EEH R EE STAGESSTAGES
Stage 1: formation of UDP-glucose
Stage 2: E longation
Stage 3: B ranchFormation
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Glycogen Synthesis
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R
Stage 3:
R1 2 3 4 5 6
1
2
3
45
6
7
branching enzymeamylo 1,4 1,5transglycosylase
glycogen
UDP
UDP
[glucose] 1
[glucose] n+1
o
pyrophosphatase UTP
PPi2Pi
glucose-6-P
glucose-1-
PH2O
phosphoglucomutase
UDP-glucosepyrophosphorylaseMg2+
Stage 1:
1o
Stage 2: UDP-glucose
7
GLYCOGENESISGLYCOGENESIS
1
R
TH R EE STAGESTH R EE STAGESS tage 1 : formation of UDP-glucose
S tage 2 : Elongation
Stage 3: B ranch Formation
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GLYCOGEN METABOLISMGLYCOGEN METABOLISM
T he action of adrenaline andglucagon on glycogen
metabolism. T he mechanismof action is as follows.T he binding of adrenaline or
glucagon activates adenylcyclase via a G-protein-coupled pathway (not shown).
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Adenyl cyclase catalyses the
formation of cAMP, whichactivates a cAMP-dependentprotein kinase (protein kinase A).
This enzyme contains tworegulatory (R) and two catalytic (C)subunits. cAMP binds to theregulatory subunits, allowing theactive catalytic subunits to
dissociate.
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cAMP-dependent protein kinase catalysesphosphorylation of:
y phosphorylase b kinase, activating it;y glycogen synthase, inhibiting it;y protein phosphatase-inhibitor-l, activating
it, thus enabling it to inhibit proteinphosphatase-l. (Ca2+ released bycontracting muscle also helps activate
phosphorylase b kinase.)y phosphorylation and activation of
glycogen phosphorylase by phosphorylaseb
kinase activates glycogen breakdown.
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LIVE R GLYCOGENLIVE R GLYCOGEN
PHOSPHO R YLASEPHOSPHO R YLASE
G lucose allosterically inhibits liver glycogen phosphorylase a .
binding of glucose causes conformationalchange; thus converting it to phosphorylase b (the inactive form).glucose, inhibits glycogen breakdown.glucose-6-phosphate also inhibits
phosphorylase but activates glycogensynthase
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M U SCLE GLYCOGENM U SCLE GLYCOGEN
PHOSPHO R YLASEPHOSPHO R YLASE
Th e main allosteric control iseffected by 5 AMP and CA2+. Formaximal activation, t h e enzymealso requires p h osp h orylation.
AMP is an indicator of t h e energystatus of t h e cell. Hig h levels of
AMP signal low energy status (i.e.low A T P),
AMP allosterically activatesp h osp h orylase b , t h is increasesglycogen breakdown in order toprovide energy for musclecontraction.
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Stimulation and in h ibition of glycogendegradation
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