T2 L6 Glycogen metabolism in muscle & liver Flashcards

1
Q

Describe glycogen

A

Polysaccharide storage form of glucose in the body
Stored in granules in liver & muscle as an energy reserve
Formed from dietary glucose by glycogenesis

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2
Q

How is glycogen degraded?

A

By glycogenolysis pathway to produce glucose-1-phosphate

Glucose-1-phosphate is converted to free glucose & exported into the bloodstream to maintain plasma glucose levels.

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3
Q

What is the structure of glycogen?

A

Forms granules within cells
Highly branched polysaccharide of glucose
Consists of alpha-1,4 linked glucose molecules with an alpha-1,6 branch every 8-14 residues. This provides a large number of ends for phosphorylase & glycogen synthase to act on to ensure rapid breakdown & resynthesis.

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4
Q

How much does glycogen storage weigh?

A

In the fed state glycogen makes up 10% of the weight of the liver & 2% of the weight of muscle
40% of human body weight is muscle
2.5% of human body weight is liver
Liver contains less glycogen than is required to sustain glucose metabolism for 24 hours, therefore de novo synthesis is required by gluconeogenesis

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5
Q

What is the equation for glycogen breakdown?

A

Glucose –> glucose-1-phosphate glucose-6-phosphate

Phosphate group is either on carbon 6 or carbon 1. G-1-P is used to build up glycogen molecules

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6
Q

What does phosphoglucomutase do?

A

It catalyses the reversible conversion of glucose-1-phosphate to glucose-6-phosphate

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7
Q

What happens to glycogen stores between meals?

A

They fall as glycogen is released from liver glycogen to stabilise the concentration of glucose in the blood
Glycogen stores are mobilised overnight to help maintain blood glucose concentration

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8
Q

How are the alpha-1,4 linkages broken?

A

By phosphorolysis
Catalysed by glycogen phosphorylase enzyme
Removes single units from non-reducing ends of glycogen to form glucose-1-phosphate
ATP is not involved

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9
Q

What is the major enzyme for controlling glycogen breakdown?

A

Glycogen phosphorylase
Breaks bond between alpha-1,4 linked glucose residues by adding a phosphate to produce glucose-1-phosphate in a phosphorolysis reaction

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10
Q

What is glycogen formed by?

A

UDP glucose - high energy form of glucose

Consumption of UTP is energetically equivalent to ATP consumption

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11
Q

What does hexokinase catalyse?

A

The conversion of glucose to glucose-6-phosphate

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12
Q

What does phosphoglucomutase catalyse?

A

The conversion of glucose-6-phosphate to glucose-1-phosphate

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13
Q

What does glycogen synthase do?

A

Adds glucose units in an alpha-1,4 linkage onto the glycogen chain using UDP-glucose

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14
Q

What is the priming function carried out by?

A

The glycogenin protein as glycogenin can accept the first glucose residue & doesn’t dissociate

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15
Q

How are branches formed?

A

A branching enzyme transfers a block of 7 residues from a growing chain to create a new branch with an alpha-1,6 linkage.
The new branch can’t be within 4 residues of a pre-existing branch due to conformation

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16
Q

Why is glycogen a good energy store?

A

It can be mobilised rapidly
Phosphorylase & glycogen synthase are sensitive to regulation by hormones, stress & muscle contraction
Branched structure provides a large number of ends

17
Q

Why is glycogen a bad energy store?

A

Hydrophilic & associates with water which increases the overall weight & bulk

18
Q

When is glycogen mobilisation accelerated?

A

Starvation in the liver when glucose is required for glycolysis by the brain & RBC
During vigorous exercise in muscle to fuel glycolysis

19
Q

When is glycogen synthesis activated?

A

To replenish liver glycogen stores after feeding
To replenish muscle stores when exercise stops
Promoted by insulin
Requires energy input

20
Q

What allosterically regulates glycogen phosphorylase?

A

AMP
ATP
Glucose-6-phosphate

21
Q

What is allosteric regulation?

A

Modulation of enzyme activity through reversible binding of small molecules to the enzymes at sites distinct from the active site

22
Q

What does AMP do to phosphorylase?

A

Activates it

Present when ATP is depleted during muscle contraction

23
Q

What do ATP & glucose-6-phosphate do to phosphorylase?

A

They inhibit it
Compete with AMP binding
Signs of high energy level
Inhibit glycogen breakdown

24
Q

How does covalent modification regulate glycogen metabolism?

A

Mediated by addition & removal of a phosphate group
Phosphorylation is catalysed by protein kinases - reversible modification
Dephosphorylation is catalysed by protein phosphatases

25
Q

How is phosphorylase activated?

A

By cAMP dependent phosphorylation
cAMP cascade causes phosphorylation of a serine hydroxyl of muscle glycogen phosphorylase which promotes transition to the active state