BCH 361: Chapter 24: Glycogen Degradation

Glycogen stores

glucose in liver and muscle

Glycogen is a

highly branched homopolymer of glucose present in all tissues

The largest stores of glycogen are in

liver and muscle

The liver breaks down

glycogen and releases glucose to the blood to provide energy for the brain and red blood cells.

Muscle glycogen stores are mobilized to provide energy for what?

muscle contraction

Glycogen contains ___ types of glycosidic bonds

two

What two types of glycosidic bonds does glycogen have?

- a-1,4-glycosidic bond
- a-1,6-glycosidic bond

Glycogen Phosphorylase breaks down

glycogen

Glycogen phosphorylase degrades glycogen from the

nonreducing ends of the glycogen

Phosphorylase can only remove the non-reducing end glucose with an

a-1,4 glycosidic bond and releases glucose 1-phosphate

glucose-1-phosphate is converted to what?

glucose 6-phosphate

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

phosphoglucomutase

Phosphorylase uses _______; Kinase uses ___

- inorganic phosphate (HPO4)
- ATP

debranching enzyme

removes oligosaccharides from a branch in glycogen or starch

Glycogen phosphorylase CANNOT

cleave near branch points

How many sugars away do glycogen phosphorylase stop?

they stop four sugars away from the branching point.

A (1) transferase shifts

a small oligosaccharide near the branch point to a nearby chain to be cleaved by the phosphorylase.

The (2) α1-6-glucosidase

removes a α1-6 linked glucose without phosphorylation.

Glucose 1-Phosphate—>

glucose 6-Phosphate—>glucose

Phosphoglucomutase converts

glucose 1 phosphate to glucose 6 phosphate

What converts Glucose-1-Phosphate to Glucose-6-Phosphate?

Phosphoglucomutase

What intermediate does phosphoglucomutase convert glucose-1 phosphate to in order to make glucose-6-phosphate?

glucose 1, 6-bisphosphate intermediate

Liver Glucose 6-phosphatase (not in muscle) converts glucose 6-phosphate to

free glucose (to be transported)

The free glucose is released into the blood for

use by other tissues such as the brain and red blood cells.

What state of glycogen phosphorylase is favored in A form?

R state

What state of glycogen phosphorylase is favored in B form?

T state

Is R state more or less active than T state?

more active

Is T state more or less active than R state?

less active

What makes R state more active than T state?

A serine residue in R state is phosphorylated, but the amino acid residues are not phosphorylated in T state

Muscle phosphorylase is regulated by

intracellular energy charge

In muscle, the default form of the phosphorylase is the

b form in the T state (less active). The b form allows the enzyme to be regulated by energy charge alone.

When energy is needed, as signaled by

an increase in the concentration of AMP, the phosphorylase binds AMP, which stabilizes the R state (more active).

The T state of the phosphorylase (less active) is stabilized by

ATP and glucose 6-phosphate.

Liver phosphorylase is regulated by

glucose level

1. A key role of the liver

is to maintain adequate blood levels of glucose.

2. As a result of the livers key role, the default state of liver phosphorylase is the

a form in the R state (always active).

3. In essence, liver phosphorylase is

always prepared to generate blood glucose unless signaled otherwise.

4. Glucose is a negative regulator of

liver phosphorylase, facilitating the transition from the R state to the T state.

5. Liver phosphorylase and muscle phosphorylase are ____.

isozymes

Does liver enzyme respond to energy charge?

no

Phosphorylase kinase converts

Glycogen phosphorylase from the unphosphorylated b state (less active) to the phosphorylated a state (more active)

Phosphorylase kinase itself is activated by both

1) phosphorylation and (2) Ca2+ binding.

(1) Phosphorylase kinase is phosphorylated by

protein kinase A (PKA)

2) The δ (delta) subunit of phosphorylase is the

calcium sensor calmodulin

What turns on glycogen degradation?

glucagon and epinephrine

Hormone Glucagon is released by

alpha cells in the pancreas in response of low blood sugar, affecting liver mostly.

Epinephrine (adrenaline) is released by

the adrenal gland in response to muscle activity & stress, including low blood sugar.

What is epinephrine derived from?

Tyrosine

Glucagon (in liver) and epinephrine (in muscle) initiate

G-protein cascades that result in the production of cAMP

Cyclic AMP activates

protein kinase A, which phosphorylates and activates phosphorylase kinase, which converts glycogen phosphorylase b to the a form, activating glycogen degradation.

How to turn off Glycogen degradation?

1. The inherent GTPase activity of the G protein renders these proteins inactive, i.e. eventually G protein will hydrolyze GTP into GDP.
2. Phosphodiesterase converts cAMP into AMP, which does not stimulate protein kinase A.
3. Protein phosphatase 1 removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, thereby inactivating the enzymes.

What does glycogen depletion correlate with?

fatigue