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. UDPglucose (Fig. 1) is synthesized from glucose 1-phosphate and UTP by UDP–glucose pyrophosphorylase (Fig. 2. 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. 3).]

Figure 1: bThe structure of UDP-glucose, a nucleotide sugar.

Figure 2: Glycogen synthesis. UDP and UTP = uridine di- and triphosphates; PPi = pyrophosphate; Pi = inorganic phosphate.

Figure 3: Interconversion of glucose 6-phosphate and glucose 1-phosphate by phosphoglucomutase. and = phosphate.
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. 2). 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
Elongation of a glycogen chain involves the transfer of glucose from UDPglucose to the nonreducing end of the growing chain, forming a new glycosidic bond between the anomeric hydroxyl group of carbon 1 of the activated glucose and carbon 4 of the accepting glucosyl residue (see Fig. 2). [Note: The nonreducing end of a carbohydrate chain is one in which the anomeric carbon of the terminal sugar is linked by a glycosidic bond to another molecule, making the terminal sugar nonreducing .] The enzyme responsible for making the α(1→4) linkages in glycogen is glycogen synthase. [Note: The UDP released when the new α(1→4) glycosidic bond is made can be phosphorylated to UTP by nucleoside diphosphate kinase (UDP + ATP ⇔ UTP + ADP.]

D. Branch formation
If no other synthetic enzyme acted on the chain, the resulting structure would be a linear (unbranched) chain of glucosyl residues attached by α(1→4) linkages. Such a compound is found in plant tissues and is called amylose. In contrast, glycogen has branches located, on average, eight glucosyl residues apart, resulting in a highly branched, tree-like structure  that is far more soluble than the unbranched amylose.

Branching also increases the number of nonreducing ends to which new glucosyl residues can be added (and also, as described in IV. below, from which these residues can be removed), thereby greatly accelerating the rate at which glycogen synthesis can occur and dramatically increasing the size of the glycogen molecule.
1. Branch synthesis: Branches are made by the action of the branching enzyme, amylo-α(1→4)→α(1→6)-transglycosylase. This enzyme removes a set of six to eight glucosyl residues from the nonreducing end of the glycogen chain, breaking an α(1→4) bond to another residue on the chain, and attaches it to a nonterminal glucosyl residue by an α(1→6) linkage, thus functioning as a 4:6 transferase. The resulting new, nonreducing end (see “i” in Fig. 2), as well as the old nonreducing end from which the six to eight residues were removed (see “o” in Fig. 2), can now be further elongated by glycogen synthase.
2. Additional branch synthesis: After elongation of these two ends has been accomplished, their terminal six to eight glucosyl residues can be removed and used to make additional branches.

مواضيع ذات صلة

آلية عمل المجموعة الأولى من الهرمونات

الهرمونات وآليات الاستتباب

تدرك (تقويض) الهرمونات وتعطيلها

نقل الهرمونات في البلازما

تغاير خزن الهرمونات وإفرازها

تخليق POMC ومعالجته

The Amino Acids

Absorption & Transport of Transition Metals

Physiologic Roles of The Essential Transition Metals

تخليق الأنجيوتنسين

تخلیق PTH

تخليق الأنسولين