Regulation of pro- and macroglycogen and glycogen-associated enzymes during rest and exercise
Due to its large mass, skeletal muscle contains the largest depot of stored carbohydrate in the body in the form of glycogen. Previous studies have shown that glycogen is not homogenous but comprised of two different forms, pro- (PG) and macroglycogen (MG). These two forms contain the same amount of protein, but differ in their amounts of attached carbohydrate. The first study examined the catabolism of PG and MG over a range of glycogen concentrations. Subjects performed high-intensity exercise and muscle biopsy samples were analyzed for PG, MG, hexose-monophosphates, and glycogen phosphorylase (GP) acting. Results showed differential degradation of PG and MG and that pre-exercise glycogen concentration was key in mediating glycogen metabolism during exercise. More glycogen was catabolized when concentrations were elevated; however, this was not always reflected in the activity of GP. The second study examined glycogenin, a self-glycosylating protein primer which initiates glycogen granule formation. Key findings showed glycogenin to be present in proportion to total, PG and MG concentrations in resting human skeletal muscle suggesting it is a potential regulator of glycogen metabolism. This led to the third study where glycogenin activity and gene expression (mRNA) were investigated in relation to PG, MG and total glycogen concentration post-exercise. Results showed PG resynthesis was four times that of the resynthesis in the MG pool. Glycogenin gene expression and activity more than doubled and reached resting levels within the first time period (30 min), indicating that glycogenin may have to be translated and transcribed in order for PG resynthesis to occur. In summary, this thesis has expanded knowledge of glycogen metabolism by showing; (i) PG, MG are metabolically distinct having differential rates of synthesis and degradation, (ii) glycogen is a regulator of its own metabolism, the type and concentration of glycogen influences its regulation, (iii) glycogenin is present in proportion to PG and MG concentration, and (iv) glycogenin is a dynamic protein that is important in the restoration of glycogen stores following exercise.