BIOC/DENT/PHCY 230 LECTURE 9

1. BIOC/DENT/PHCY 230 LECTURE 9

2. 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

4. 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

5. What are the chemical requirements for glycogen mobilisation? • glycogen contains two types of bond: a-1,4 and a-1,6 glycosidic bonds

6. 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

7. Glycogen phosphorylase catalyses the cleavage of the a-1,4 glycosidic bonds non-reducing end glucose-1-phosphate

8. 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 botha-1,6 glucosidase activity anda-1,4 a-1,4 glucantransferase activity

9. Glucose-1-phosphate must be converted to glucose-6-phosphate before it can enter glycolysis • catalysed by phosphoglucomutase

11. 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)

12. AMP

13. Glucagon stimulates glycogen phosphorylase via a receptor mediated signalling pathway

14. A closer look at the activation of adenylate cyclase

15. phosphodiesterase phosphatase

18. 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