Glycogenolysis

.

Glycogen Metabolism

•Glycogen DegradationReactions and EnzymesSites of Storage and Use

•Regulation of Glycogen Metabolism-Mechanisms of Regulation

Hormonal Control of Enzymes

Glycogen Structure

Linkages all a; 1->4 chains and 1->6 branches

Branches every 8-12 residues allow compact, less fibrillar structure and high number of non-reducing ends

Most Glycogen is Stored in Liver and Muscle

Liver - 6-8% glycogen, wet weight

Muscle - 1-2% glycogen, wet weight

Glycogen plays different roles in liver and muscle

Liver supplies tissues with Glc from glycogen during fasting

In muscle, conversion of glycogen to Glc is important during strenuous exercise, and conversion of Glc to glycogen plays important role in lowering blood Glc after feeding

Liver glycogen stores are partially depleted, even during

short fasts

Depletion of Liver Glycogen over 24 h

Two major enzymes participate in all glycogen

degradation:

Glycogen phosphorylase

and

Glycogen debranching enzyme

Glycogen phosphorylase removes most glucose residues

as Glc-1-P

toward -1->4 linkages

from non-reducing ends, releasing successive Glc-1-P residues,

BUT only to within 4 residues of a branchpoint

Molecules left after complete phosphorylase digestion of glycogen are

Limit Dextrins

Non-reducing ends

Reducing end

Glycogen Debranching Enzyme accesses

branchpoints and residues close to branchpoints

The Debranching Enzyme accomplishes this using two different enzyme activities on the same polypeptide;

1,4->1,4 Glucan transferase and

1,6 Glucosidase

-1,4->1,4 Glucosyl transferase activity transfers three residues to another chain

2. Amylo -1->6 Glucosidase- hydrolytic activity releases Glc

1

2

Major Final Product of Glycogen Degradation is Glc-

1-P

In muscle, glycogen is degraded to provide an immediate energy source. Therefore, Glc-6-P is needed for entry into glycolysis.

In liver, glycogen is a storage form that helps provide Glc to peripheral tissues in times of low circulating sugar. Therefore, liver needs to produce free Glc.

To Complete Glycogen Degradation, Need to

Convert Glc-1-P to Useful Form

MUSCLE:

Phosphoglucomutase

Glc-1-P ----------------------> Glc-6-P ----------> Glycolysis

LIVER:

Phosphoglucomutase Glucose-6-Phosphatase

Glc-1-P ------------------------> Glc-6-P --------------> Glucose

Glycogen Degradation

(red. end)

Regulation of Glycogen Metabolism

Glycogen synthase and glycogen phosphorylase are the targets of allosteric modulators and of covalent, reversible modification (phosphorylation)

Glycogen Phosphorylase Regulation

Glycogen phosphorylase is regulated by allosteric modulators:

AMP (+) and Glc, Glc-6-P, ATP (-)

Thus, both energy status and Glc availability impinge on activity

This control is integrated with regulation by phosphorylation

Allosteric regulation of phosphorylase activity

Glycogen phosphorylase is activated by

phosphorylationPhosphorylase kinase activates glycogen phosphorylase by phosphorylating one site on each subunit of the homodimer

Phosphorylase a is more active, and cannot be activated further by AMP; CAN be inhibited by Glc and ATP

Phosphorylase b is less active, and can be activated by AMP

Phosphorylase Regulation