Carbohydrate metabolism in the
fasted state
 the body needs to ensure there is a constant supply
of glucose for tissues like the brain
 this can be achieved by mobilising body stores of
glucose (glycogenolysis) or synthesising glucose de novo
 the stimulation for the mobilisation and/or
synthesis of glucose can come from a number of
 glucagon, adrenaline and cortisol can all increase the
mobilisation of glucose
Glycogen mobilisation
 the two main stores of
glycogen are muscle and liver
 muscle glycogen is for local use
 liver glycogen helps maintain
plasma glucose levels
 the branched nature of
glycogen allows for the rapid
mobilisation of glucose from these
stores under the appropriate
What are the chemical requirements for
glycogen mobilisation?
 glycogen contains two types of bond:
a-1,4 and a-1,6 glycosidic bonds
Glycogenolysis requires three different
enzyme activities
1) an a-1,4 glucosidase activity
2) an a-1,6 glucosidase activity
3) an a-1,4
a-1,4 glucantransferase activity
Glycogen phosphorylase catalyses the cleavage
of the a-1,4 glycosidic bonds
non-reducing end
Glycogen phosphorylase
can not digest all of the
glucose units in a branch
 GP can only cleave down to 4
or 5 residues from a branch
 to allow the process to
continue a “debranching
enzyme” is required
 this enzyme has both
a-1,6 glucosidase activity and
a-1,4 a-1,4 glucantransferase
Glucose-1-phosphate must be converted
to glucose-6-phosphate before it can
enter glycolysis
 catalysed by phosphoglucomutase
Regulation of glycogenolysis
 glycogen phophorylase can be regulated both by
covalent modification and allosteric interactions
 glycogen phosphorylase is found in two “active
phosphorylase a is relatively active
phosphorylase b is relatively inactive (but still
active none the less)
Glucagon stimulates
phosphorylase via a
receptor mediated
signalling pathway
A closer look at the activation of
adenylate cyclase
Co-ordinate regulation of glycogenolysis
and glycogen synthesis
 both glycogenolysis and glycogen synthesis occur in
the cytosol
 both pathways have G-6-P and G-1-P as intermediates
 need some mechanism to only have one pathway active
at any one time
Those signals which activate glycogen phosphorylase
inhibit glycogen synthase