BIOC/DENT/PHCY 230 LECTURE 9

Carbohydrate metabolism in the fasted state o the body needs to ensure there is a constant supply of glucose for tissues like the brain o this can be achieved by mobilising body stores of glucose (glycogenolysis) or synthesising glucose de novo (gluconeogenesis) o the stimulation for the mobilisation and/or synthesis of glucose can come from a number of sources o glucagon, adrenaline and cortisol can all increase the mobilisation of glucose

Glycogen mobilisation o the two main stores of glycogen are muscle and liver o muscle glycogen is for local use o liver glycogen helps maintain plasma glucose levels o 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? o 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 o GP can only cleave down to 4 or 5 residues from a branch point o 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 o catalysed by phosphoglucomutase

Regulation of glycogenolysis o glycogen phophorylase can be regulated both by covalent modification and allosteric interactions o 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 o both glycogenolysis and glycogen synthesis occur in the cytosol o both pathways have G-6-P and G-1-P as intermediates o need some mechanism to only have one pathway active at any one time Those signals which activate glycogen phosphorylase inhibit glycogen synthase