lect9

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: 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

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 a-1,6 glucosidase activity and a-1,4 a-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