2 glycogen metabolism

8/9/2019 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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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


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

2 glycogen metabolism

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