C. Glycogen store fluctuation
Liver glycogen stores increase during the well-fed state (see p. 323) and are depleted during a fast (see p. 329). Muscle glycogen is not affected by short periods of fasting (a few days) and is only moderately decreased in prolonged fasting (weeks). Muscle glycogen is synthesized to replenish muscle stores after they have been depleted following strenuous exercise. [Note: Glycogen synthesis and degradation go on continuously. The difference between the rates of these two processes determines the levels of stored glycogen during specific physiologic states.]
III. SYNTHESIS (GLYCOGENESIS)
Glycogen is synthesized from molecules of α-D-glucose. The process occurs in the cytosol and requires energy supplied by ATP (for the phosphorylation of glucose) and uridine triphosphate (UTP).
A. Uridine diphosphate glucose synthesis α-D-Glucose attached to uridine diphosphate (UDP) is the source of all the glucosyl residues that are added to the growing glycogen molecule. UDP-glucose (Fig. 11.4) is synthesized from glucose 1-phosphate and UTP by UDP–glucose pyrophosphorylase (Fig. 11.5). Pyrophosphate (PPi), the second product of the reaction, is hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase. The hydrolysis is exergonic, insuring that the UDP–glucose pyrophosphorylase reaction proceeds in the direction of UDP-glucose production. [Note: Glucose 1-phosphate is generated from glucose 6-phosphate by phosphoglucomutase. Glucose 1,6-bisphosphate is an obligatory intermediate in this reversible reaction (Fig. 11.6).]
B. Primer requirement and synthesis
Glycogen synthase makes the α(1→4) linkages in glycogen. This enzyme cannot initiate chain synthesis using free glucose as an acceptor of a molecule of glucose from UDP-glucose. Instead, it can only elongate already existing chains of glucose and, therefore, requires a primer. A fragment of glycogen can serve as a primer. In the absence of a fragment, the homodimeric protein glycogenin can serve as an acceptor of glucose from UDP-glucose (see Fig. 11.5). The side-chain hydroxyl group of tyrosine-194 in the protein is the site at which the initial glucosyl unit is attached. Because the reaction is catalyzed by glycogenin itself via autoglucosylation, glycogenin is an enzyme. Glycogenin then catalyzes the transfer of at least four molecules of glucose from UDP-glucose, producing a short, α(1→4)-linked glucosyl chain. This short chain serves as a primer that is able to be elongated by glycogen synthase, which is recruited by glycogenin, as described in C. below. [Note: Glycogenin stays associated with and forms the core of a glycogen granule.]
C. Elongation by glycogen synthase