Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Carbohydrate Metabolism
Glycogen Synthesis and Degradation
Glycogen Breakdown (Glycogenolysis)

It is well known that phosphorolytic degradation plays a key role in the mobilization of Polysaccharides *.

* In Human and Animal Tissues, the enzyme α-amylase, which catalyzes the Cleavage of glucose residues from the Glycogen molecule via an α-1,4-linkage, was also discovered by Soviet biochemists E.L. Rosenfeld and I.A. Popova. However, phosphorylases play the leading role in glycogen degradation within Cells.

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Fig. 10.1. Hormonal Regulation of the phosphorolytic cleavage of a glucose residue from glycogen.

Phosphorylases convert polysaccharides (specifically glycogen) from a storage form into a metabolically active form; in the presence of phosphorylase, glycogen breaks down to form a sugar phosphate—glucose (glucose-1-phosphate)—without prior cleavage into larger polysaccharide fragments. In general terms, this reaction can be represented as follows:

(C₆H₁₀O₅)_n + Н₃РО₄ -> (C₆H₁₀O₅)_n-1 + Глюкозо-1-фосфат,

where (С₆Н₁₀О₅)_n denotes the polysaccharide chain of glycogen, and (С₆Н₁₀О₅)_n-1 represents the same chain shortened by one glucose residue.

Fig. 10.1 illustrates The process of glycogen degradation to glucose-1-phosphate and the involvement of cAMP in this process. The enzyme phosphorylase exists in two forms, one of which (phosphorylase a) is active, while the other (phosphorylase b) is normally inactive. Both forms can dissociate into subunits. Phosphorylase b consists of two subunits, whereas phosphorylase a consists of four. The conversion of phosphorylase b into phosphorylase a is brought about by protein phosphorylation:

2 Фосфорилаза b + 4 АТФ -> Фосфорилаза а + 4 АДФ.

This reaction is catalyzed by an enzyme called phosphorylase b kinase. It has been established that this kinase can exist in both active and inactive forms. Inactive phosphorylase kinase is converted into the active form under METABOLISM/18.html">The Influence of protein kinase (phosphorylase kinase kinase)—specifically, a cAMP-dependent protein kinase.

The active form of the latter is generated with the participation of cAMP, which in turn is formed from ATP through the action of the enzyme adenylate cyclase, stimulated notably by adrenaline and Glucagon. An increase in Blood adrenaline levels triggers this complex cascade of reactions, leading to the conversion of phosphorylase b into phosphorylase a and, consequently, the release of glucose as glucose-1-phosphate from the stored polysaccharide glycogen. The reverse conversion of phosphorylase a into phosphorylase b is catalyzed by the enzyme phosphatase (this reaction is practically irreversible).

The glucose-1-phosphate produced by the phosphorolytic breakdown of glycogen is converted into glucose-6-phosphate by phosphoglucomutase. This reaction requires the phosphorylated form of phosphoglucomutase—that is, its active form—which, as noted earlier, is formed in the presence of glucose-1,6-bisphosphate *.

The formation of free glucose from glucose-6-phosphate in the Liver occurs under the influence of glucose-6-phosphatase. This enzyme catalyzes the hydrolytic removal of phosphate:

* It has now been established that a phosphorylated Serine residue is present in the catalytic center of the active form of the phosphoglucomutase molecule. During catalysis, this phosphoryl group is presumably transferred to the hydroxyl group at C-6 of glucose-1-phosphate, yielding glucose-1-bisphosphate. Subsequently, the phosphoryl group of this intermediate is transferred to the serine residue in the active center. This results in the formation of glucose-6-phosphate and the regeneration of the phosphorylated enzyme.

Fig. 10.2. Degradation and synthesis of glycogen (schematic).

Bold arrows indicate the degradation pathway, and thin arrows represent the synthesis pathway. The numbers designate Enzymes: 1 - phosphorylase; 2 - phosphoglucomutase; 3 - glucose-6-phosphatase; 4 - hexokinase (glucokinase); 5 - glucose-1-phosphate uridylyltransferase; 6 - glycogen synthase.

It should be noted that, unlike unesterified glucose, phosphorylated glucose cannot readily diffuse out of cells. The liver contains the hydrolytic enzyme glucose-6-phosphatase, which ensures the rapid efflux of glucose from this organ. In contrast, glucose-6-phosphatase is practically absent in Muscle tissue.

Fig. 10.2 reflects current concepts regarding the pathways of glycogen degradation and synthesis in the liver *.

It can be considered that maintaining a constant blood glucose concentration is the result of two simultaneous processes: The entry of glucose into the blood from The Liver and its uptake from the blood by tissues, where it is utilized primarily as an energy source.

In tissues (including the liver), glucose breakdown proceeds via two main pathways: anaerobic (in the absence of oxygen) and aerobic, which requires oxygen to take place.