Question

3. Glycogen Degradation

a) What are the steps in the breakdown of glycogen?

b) Glycogen phosphorylase exists in different forms and conformations under different physiological conditions. In a resting muscle, MOST of the phosphorylase will be in which form and which state?

c) How do hormones regulate glycogen breakdown?

Answer 1

ANSWER A & C

Glycogen Phosphorylase catalyzes breakdown of glycogen into Glucose-1-Phosphate (G1P). The reaction that produces G1P from glycogen is a phosphorolysis, not a hydrolysis reaction. The distinction is that hydrolysis reactions use water to cleave bigger molecules into smaller ones, but phosphorolysis reactions instead use phosphate for the same purpose. Note that the phosphate is just that - it does NOT come from ATP. Since ATP is NOT used to put phosphate on G1P, the reaction saves the cell energy. In addition, the phosphate on the G1P helps prevent the molecule from leaving the cell as it is. Glycogen phosphorylase will only act on non-reducing ends of a glycogen chain that are at least 5 glucoses away from a branch point. A second enzyme, Glycogen Debranching Enzyme (GDE), is therefore needed to convert alpha(1-6) branches to alpha(1-4) branches). GDE acts on glycogen branches that have reached their limit of hydrolysis with GP. It acts to transfer a trisaccharide from a 1,6 branch onto an adjacent 1,4 branch, leaving a single glucose at the 1,6 branch. Note that the enzyme also catalyzes the hydrolysis of the remaining glucose at the 1,6 branch point Thus, the breakdown products from glycogen are G1P and glucose (mostly G1P, however). Glucose can, of course, be converted to Glucose-6-Phosphate (G6P) as the first step in glycolysis by either hexokinase or glucokinase.

G1P can be converted to G6P by action of an enzyme called Phosphoglucomutase. the mechanism of action of phosphoglucomutase involves formation of a transient intermediate of glucose-1,6-bisphosphate before the G6P is produced. This reaction is readily reversible, allowing G6P and G1P to be interconverted as the concentration of one or the other increases. This is important, because phosphoglucomutase is needed to form G1P for glycogen biosynthesis.

ANSWER B

muscles do not have G6Pase so that when G6P is produced from glycogen breakdown, it can enter glycolysis. When you begin exercise, most of the glycogen phosphorylase is in the GPb form and inactive.