Glycogen Synthesis

Glycogen synthesis (glycogenesis)

The process of storing glucose by building glycogen molecules

Glycogen

A highly branched polymer of glucose used for energy storage in animals

Glycogenolysis

The breakdown of glycogen into glucose units

Main purpose of glycogen synthesis

Store excess glucose for later energy use

Two primary locations of glycogen storage

Liver and skeletal muscle

Function of liver glycogen

Helps maintain blood glucose levels between meals

Function of skeletal muscle glycogen

Provides glucose for ATP production within muscle cells

Why can liver release glucose into the bloodstream?

It contains glucose-6-phosphatase

Why can't skeletal muscle release glucose derived from glycogen into the bloodstream?

It lacks glucose-6-phosphatase

What enzyme converts G6P into free glucose?

Glucose-6-phosphatase

Three major metabolic fates of glucose-6-phosphate

Glycolysis and glycogen synthesis and pentose phosphate pathway

What pathway uses G6P to produce ATP?

Glycolysis

What pathway uses G6P to produce NADPH?

Pentose phosphate pathway

What pathway uses G6P for glucose storage?

Glycogen synthesis

What type of polymer is glycogen?

A highly branched glucose polymer

What bond forms the linear chains of glycogen?

Alpha-1 4 glycosidic bonds

What bond forms branch points in glycogen?

Alpha-1 6 glycosidic bonds

How frequently do glycogen branches occur?

Approximately every 12 glucose residues

Nonreducing ends

Outer ends of glycogen branches where glucose units are added or removed

Why is glycogen highly branched?

Branching increases the number of nonreducing ends for rapid synthesis and breakdown

What happens when glycogen has more nonreducing ends?

More enzymes can add or remove glucose simultaneously

Where is glycogenin located in a glycogen particle?

At the center or core

Glycogenin

A protein that initiates glycogen synthesis by creating a glucose primer

Glycogen synthase

The main enzyme that extends glycogen chains by forming alpha-1 4 bonds

Why can't glycogen synthase initiate glycogen synthesis?

It requires an existing glucose primer

What molecule provides the primer for glycogen synthase?

Glycogenin

What molecule does glycogenin use to initiate glycogen synthesis?

UDP-glucose

What amino acid residue receives the first glucose on glycogenin?

Tyrosine

What type of bonds does glycogenin form while building the primer?

Alpha-1 4 glycosidic bonds

What happens after glycogenin creates a short primer?

Glycogen synthase takes over and extends the chain

Does glycogenin remain attached to the glycogen particle?

Yes it remains at the core

UDP-glucose

The activated form of glucose used during glycogen synthesis

What is the direct substrate of glycogen synthase?

UDP-glucose

Why must glucose be activated before glycogen synthesis?

Free glucose and glucose-1-phosphate are not reactive enough for efficient chain elongation

What nucleotide triphosphate is used to activate glucose?

UTP

What enzyme converts glucose-6-phosphate into glucose-1-phosphate?

Phosphoglucomutase

Phosphoglucomutase

Enzyme that reversibly converts G6P and G1P

Direction of phosphoglucomutase during glycogen synthesis

G6P → G1P

Direction of phosphoglucomutase during glycogen breakdown

G1P → G6P

Is the phosphoglucomutase reaction reversible?

Yes

What enzyme synthesizes UDP-glucose?

UDP-glucose pyrophosphorylase

UDP-glucose pyrophosphorylase

Enzyme that converts glucose-1-phosphate and UTP into UDP-glucose and PPi

Substrates of UDP-glucose pyrophosphorylase

Glucose-1-phosphate and UTP

Products of UDP-glucose pyrophosphorylase

UDP-glucose and pyrophosphate

UDP-glucose formation reaction

G1P + UTP → UDP-glucose + PPi

Pyrophosphate (PPi)

A molecule containing two linked phosphate groups released during UDP-glucose formation

What enzyme hydrolyzes pyrophosphate?

Inorganic pyrophosphatase

What are the products of pyrophosphate hydrolysis?

2 inorganic phosphate molecules

Why is PPi hydrolysis important?

It drives UDP-glucose synthesis forward

What makes the overall formation of UDP-glucose effectively irreversible?

Hydrolysis of PPi into 2 Pi

What enzyme creates glycogen branch points?

Glycogen branching enzyme

Glycogen branching enzyme

Transfers a segment of an existing glucose chain to create an alpha-1 6 linkage

What bond does the branching enzyme break?

Alpha-1 4 glycosidic bond

What bond does the branching enzyme create?

Alpha-1 6 glycosidic bond

Does the branching enzyme directly use UDP-glucose?

No it transfers glucose residues already present in the chain

Difference between glycogen synthase and branching enzyme

Glycogen synthase extends linear chains while branching enzyme creates branches

Difference between glycogenin and glycogen synthase

Glycogenin initiates the primer while glycogen synthase extends it

Three major enzymes involved in building glycogen

Glycogenin and glycogen synthase and glycogen branching enzyme

What are the two ATP-equivalent energy costs of storing dietary glucose?

One ATP for glucose phosphorylation and one UTP for glucose activation

Total energy cost of incorporating one dietary glucose into glycogen

2 ATP equivalents

Where is ATP consumed during glycogen synthesis?

Glucose → Glucose-6-phosphate

Where is UTP consumed during glycogen synthesis?

Glucose-1-phosphate → UDP-glucose

Does phosphoglucomutase directly consume ATP?

No

Does glycogen synthase directly consume ATP during chain elongation?

No it uses activated UDP-glucose

How many ATP are produced from complete oxidation of glycogen-derived glucose according to the lecture?

31 ATP

What hormone stimulates glycogen synthesis?

Insulin

What happens to glycogen synthase activity when insulin increases?

Glycogen synthase activity increases

Which form of glycogen synthase is more active?

Dephosphorylated glycogen synthase

Effect of phosphorylation on glycogen synthase

Decreases its activity

Effect of dephosphorylation on glycogen synthase

Increases its activity

Protein phosphatase 1 (PP1)

Enzyme that removes phosphate groups from glycogen synthase and activates it

What does PP1 do to glycogen synthase?

Dephosphorylates and activates it

Glycogen synthase kinase 3 (GSK3)

Kinase that phosphorylates glycogen synthase and decreases its activity

What does GSK3 do to glycogen synthase?

Phosphorylates and inhibits it

How does insulin affect GSK3?

Insulin signaling inhibits GSK3

How does insulin promote glycogen synthase activation?

It reduces inhibitory phosphorylation through GSK3 inhibition and favors dephosphorylation

What is the relationship between PP1 and GSK3?

PP1 activates glycogen synthase through dephosphorylation while GSK3 inhibits it through phosphorylation

How does PP1 help coordinate glycogen metabolism?

It promotes glycogen synthesis and helps suppress glycogen breakdown

Insulin regulation sequence

Insulin → GSK3 inhibition → Reduced glycogen synthase phosphorylation → Increased glycogen synthesis

What happens to glycogen synthesis when blood glucose is high?

Insulin promotes glycogen storage