BIOC/DENT/PHCY 230

LECTURE 9

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 (gluconeogenesis)

the stimulation for the mobilisation and/or synthesis of glucose can come from a number of sources

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 conditions

What are the chemical requirements for glycogen

mobilisation? glycogen contains two types of bond:

-1,4 and -1,6 glycosidic bonds

Glycogenolysis requires three different enzyme activities

1) an -1,4 glucosidase activity

2) an -1,6 glucosidase activity

3) an -1,4 -1,4 glucantransferase activity

Glycogen phosphorylase catalyses the cleavage of the -1,4 glycosidic bonds

non-reducing end

glucose-1-phosphate

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 point

to allow the process to continue a “debranching enzyme” is required

this enzyme has both-1,6 glucosidase activity and-1,4 -1,4 glucantransferase activity

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 forms”

phosphorylase a is relatively active

phosphorylase b is relatively inactive (but still active none the less)

AMP

Glucagon stimulates glycogen phosphorylase via a receptor mediated signalling pathway

A closer look at the activation of adenylate cyclase

phosphodiesterase

phosphatase

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