GLYCOGENESIS

Glycogenesis,
the formation of glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, from glucose. Glycogenesis takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells.
Glycogenesis is stimulated by the hormone insulin. Insulin facilitates the uptake of glucose into muscle cells, though it is not required for the transport of glucose into liver cells. However, insulin has profound effects on glucose metabolism in liver cells, stimulating glycogenesis and inhibiting glycogenolysis, the breakdown of glycogen into glucose. Compare glycogenol

Glycogenesis is an anabolic process that requires energy. It consists of the following steps:

1.

Glucose phosphorylation. The first step in glycogen synthesis is conversion of glucose to G-6-P. This reaction, catalyzed by hexokinases (glucokinase among them), was described in a previous section.

2.

Glucose-1-phosphate formation. In the second stage, phosphoglucomutase catalyzes the transfer of the phosphate group from carbon 6 to carbon 1 on the glucose molecule. G-6-P is converted to glucose-l-phosphate. Phosphoglucomutase requires Mg+ and glucose-1,6-bisphosphate as cofactors [the term bisphosphate indicates that there are two phosphates bound at different sites of the same molecule. When the phosphates are bound together by an anhydride bond, it is called diphosphate (i.e., ADP)]. The reaction is reversible.

3.

Glucose activation. Glucose-1-phosphate reacts with the high energy nucleotide uridine triphosphate (UTP) to give uridine diphosphate glucose (UDPG) and pyrophosphate (PPi). The reaction is catalyzed by uridine diphosphate-glucose pyrophosphorylase, or glucose-1-P uridyltransferase.

Inorganic pyrophosphate is rapidly hydrolyzed by the action of pyrophosphatase. Immediate disappearance of pyrophosphate makes this reaction virtually irreversible.

Glucose inclusion in the nucleotide sugar (UDPG) gives it the necessary reactivity to participate in the synthesis of glycogen. Glucose is activated by binding to UDP. The metabolic role of nucleotide sugars, such as UDPG was discovered by Luis F. Leloir.

4.

Glucose addition to the polymer backbone. At this stage, the UDPG-activated glucose is transferred to preexisting glycogen. One glycosidic linkage to carbon 4 of a terminal glucose of a glycogen chain is formed. This reaction is catalyzed by glycogen synthase, a glucosyl transferase that requires the presence of the preexisting glycogen polymeric structure, which keeps adding glucose molecules via α1→4 bonds. The reaction is practically irreversible.

5.

Branch formation. When glycogen synthase has built a glycogen chain of 10 or more glucose residues, another enzyme, amylo-α(1,4)→α(1,6)-glucantransferase (or branching enzyme), cuts a terminal segment of at least 6 glucose molecules and inserts it with an α1→6 glycosidic bond on a neighboring chain (Fig. 14.2).