Glycogen metabolism

Glycogen found mainly in Liver (blood) and muscle (local)

Synthesis of glycogen, (glycogenesis)
Degradation of glycogen (glycogenolysis)

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Glycogen synthesis

Liver glycogen is for storage and maintenance of blood

glucose between meals
After 12-18 hours of fasting the liver completely depleted of
glycogen
Muscle glycogen for local use, depleted only after vigorous
exercise. It is not affected short-term fasting (few days), and
only moderately affected by prolonged starvation (few
weeks)
Glycogen storage diseases are inherited disorders, either
abnormal glycogen or deficient mobilization cause muscle
weakness or even death

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Glycogen synthesis

The substrate is UDP-glucose

Enzyme glycogen synthase (1-4)

Branching enzyme (1-6)

Initiation need either: a. Pre-existing short chains of glycogen or b.

Glycogenin (protein found centre of glycogen granule)

Progress at non-reducing end (c4 or c6)

UDP-glucose

Phosphoglucomutase

Glucose 6-P

Glucose 1-P

UDP-glucose pyrophosphorylase

Glucose1-P + UTP

UDP-Glucose + PPi

C1 of activated Glu form a glycosidic bond with C4 of terminal Glu residue of

glycogen primer or OH of tyrosine of glycogenin primer. In the later, glycogen
initiator synthase enzyme is used.
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Branching
When chain length 10 12
glucosyle residues
Branching enzyme remove 5 8
residues to another glucose in
original chain
Link it through 1-6 (branch)
The branch grow by 1-4 linkage
The free C4 and C6 are reactive
sites (non-reducing site or
terminal)
The increasing number of
branches enhance both synthesis
and degradation
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Glycogenolysis (degradation)

Debranching

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Regulation
Different between liver and muscles due to diff. goals
Breakdown and synthesis are opposing, so that they are reciprocally regulated
i.e. when one activated other inhibited. To avoid futile cycles (waste of energy
in form of heat)
In muscles, when 4 Ca bind calmodulin, the later undergoes conformational
changes, that lead to activation of phosphorylase (glycogenolysis) by
phosphorylase kinase, also high level of AMP increase glycogenolysis
In liver Glucose inhibit phosphorylase
Phosphorylase a [P] active form:
- activated by phosphorylase kinase
- inhibited by protein phosphatase-1
Glycogen synthase a [de-P] active form
- activated by protein phosphatase-1
- inhibited by phosphrylation e.g. phosphorylase kinase
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005

Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005