Glycogenesis and Glycogenolysis

Describe the structure of glycogen

• storage form of glucose → branched

• multiple alpha-D glucose units linked by alpha(1,4) glycosidic bonds

What are the advantages of branching?

• more glucose units can be “packed” into glycogen’s structure

• prevents crystallization of glucose

The open -Oh group ends of glycogen are called

non reducing ends

The one reducing end of glycogen is “capped” by a protein called ____

glycogenin (R)

Describe liver glycogen

• maintains blood glucose conc

• increases in well-fed state

• decreases in starvation state

describe Muscle glycogen

• fuel reserve for ATP synthesis during exercise

• decreased levels due to strenuous muscle activity

• synthesizes when glycogen stores are depleted

Step 1 of glycogenesis

• glucose 6-phosphate → glucose 1-phosphate

• enzyme: phosphoglucomutase

Step 2 of glycogenesis

• glucose 1-phosphate and UTP → UDP-glucose

• enzyme: UDP-glucose pyrophosphorylase

  • hydrolyzes UTP by UDP-pyrophosphorylase

What is the role of glycogenin?

• priming glucosyltransferase

• acceptor of glucose residues

• glucose unit is attached to glycogenin via Tyr-OH group

Step 3 of glycogenesis

• glycogenin forms initiating primer

• incoming alpha-D-glucose units from UDp-glucose are transferred to the primer

Step 4 of glycogenesis

• transfer of glucose units from UDP-glucose → chain elongation of glycogen

  • enzyme: glycogen synthase

• transfer occurs at non-reducing end

Step 5 (branching) of glycogenesis

• 5-8 residues transfered from non-reducing ends to another glucose-1 phosphate residue

  • enzyme: 4:6 transferase (glucose branching enzyme)

• creates a branch point with [alpha (1,6) linkage] point

• branching allows more non-reducing ends to be created

• helps packs in more alpha-D-glucose units

Define glycogenolysis

• breakdown of glycogen to release glucose-1-phosphate and alpha-D-glucose

• catabolic pathway

Step 1 of glycogenolysis

• Shortening of glycosidic chains

• alpha (1,4) linkage of glycogen cleaved from nonreducing end

  • enzyme: glycogen phosphorylase

    • pyridoxal phosphate (prosthetic group)

• glucose 1-phosphate is released

• enzyme continues until 4 glucsoylunits (limit dextrin) remain from branch point

Step 2 of glycogenolysis

• debranching (moves 3 units)

• limit dextrin initiates action of a debranching enzyme #1

  • enzyme: 4:4 transferase enzyme

Step 3 of glycogenolysis

• lone residue attached by alpha (1,6) glycosidic bond is removed by hydrolysis

  • enzyme: 1:6 glucosidase → debranching enzyme #2

• glycogen phosphorylase is used again for degradation if needed

Step 4 of glycogenolysis

• glucose 1-phosphate → glucose 6-phosphate

  • enzyme: phosphoglucomutase

Describe how step 4 of glycogenolysis occurs in the liver

• glucose 6-phosphatase transported to the ER

  • enzyme: glucose 6-phosphatase

• glucose is released into blood stream

Describe how step 4 of glycogenolysis occurs in the muscle

• glucose 6-phosphate levels build up

  • ***muscle lacks glucose 6-phosphatase

• glycolysis starts

What is the role of glycogen phosphorylase?

works on non reducing ends until it reaches 4 residues from an alpha (1→6) branch point

What is the role of debranching enzyme #1?

transfers block of 3 residues to the non reducing end of the chain

What is the role of debranching enzyme #2?

• cleaves the remaining alpha(1→6)-linked glucose

  • becomes a free glucose unit

In the liver, ____ accelerates in the well fed state, while ____ accelerates in the fasting state

glycogenesis, glycogenolysis

In the muscle, ____ accelerates during active exercise, while ____ accelerates during rest

glycogenolysis, glycogenesis

How does regulation occur at a receptor level?

allosteric control of glycogenesis and glycogenolysis

How does regulation occur at a hormonal level?

• glycogen phosphorylase and glycogen synthase are hormonally regulated by insulin, glucagon, and E

Insulin ___ the effects of glucagon and epinephrine.

opposes

T/F: insulin favors glycogen synthesis

true

Glucagon and epinephrine favor glycogen ____

breakdown

Hormonal stimulation of glycogen synthesis

1. insulin binds to receptor tyrosine kinase

2. receptor tyrosine kinase phosphorylates insulin-sensitive kinase

3. insulin-sensitive kinase phosphorylates phosphatase-1

4. TWO OUTCOMES:

   1. Activated protein phosphatase-1 (PP-1) activates glycogen synthase → glycogen synthesis

      OR

   2. PP-1 inhibits phosphorylase kinase → activates glycogen phosphorylase

      • prevents breakdown of glycogen

      • indirect inhibition of glycogen phosphorylase

glycogen synthase exists in 2 forms:

1. a → active form, dephosphorylated

2. b → inactive form, phosphorylated

glycogen phosphorylase exists in 2 forms:

1. a → active form, phosphorylated

2. b → inactive form, dephosphorylated

Hormonal stimulation of glycogen breakdown

1. epinephrine/glucagon activates adenylyl cyclase

2. adenylyl cyclase catalyzes generation of cAMP

3. cAMP activates cAMP-dependent protein kinase

   • higher levels of cAMP = greater # of activated protein kinases

4. cAMP-dependent protein kinase phosphorylates glycogen synthase AND glycogen phosphorylase

   • glycogen synthase → inactive

   • glycogen phosphorylase → active

T/F: glycogenolysis and glycogenesis can occur at the same time

FALSE

Which substance activates glycogen synthase b in the liver?

both insulin and glucose 6-phosphate

Which statement describes possible fates for glucose 1-phosphate in skeletal muscle?

Glucose 1-phosphate can be the substrate for UDP-glucose pyrophosphorylase to make substrate for glycogen synthase.

Is glycogen phosphorylase activated, inhibited, or unaffected in response to a glucagon signal in liver tissue?

activated

In glycogen _____ glycosidic bonds occur at branch points, while all others are _____ glycosidic bonds.

(α1 → 6); (α1 → 4)

Which statement is true of glycogen synthase?

It catalyzes addition of glucose residues to the nonreducing end of a glycogen chain by formation of (α1 → 4) bonds.

The action of which three enzymes are needed to release glucose from the outer branches of glycogen so that it may be used in glycolysis?

glycogen phosphorylase; glycogen debranching enzyme; phosphoglucomutase

Which statement is true of the glycogen branching enzyme?

It catalyzes the formation of (α1 → 6) linkages during glycogen synthesis.