Textbook - BIOLOGICAL CHEMISTRY - Hubsky Y.I. - 2000

Section III. METABOLISM OF MAJOR CLASSES OF BIOMOLECULES

CHAPTER 13. CARBOHYDRATE METABOLISM. III. METABOLISM OF GLYCOGEN AND GLYCOCONJUGATES

Glycogen is an animal homopolysaccharide found in the Cytosol of Cells as microscopic granules, serving as a store of labile metabolic fuel. Glycogen acts as a reserve form of glucose; storing excess glucose as monomer molecules is impossible due to its high osmotic activity. The main Organs that store the largest amounts of glycogen are The Liver and skeletal Muscles, which can supply their own energy needs and maintain Blood glucose levels (the liver) between meals.

Glycoconjugates are complex molecules containing oligo- or polysaccharide chains linked to a peptide or lipid moiety. The normal Biosynthesis and degradation of the carbohydrate portion of glycoconjugates are essential Prerequisites for the realization of the BIOLOGICAL Functions OF Proteoglycans, Glycoproteins, and Glycolipids.

13.1. BIOSYNTHESIS AND DEGRADATION OF GLYCOGEN

The metabolic reactions of glycogen molecules are catalyzed by Enzymes structurally associated with the cytosolic granules of the polysaccharide, which control The rate of its synthesis or mobilization depending on blood glucose levels and the state of the body's regulatory systems.

Class="center">ENZYMATIC REACTIONS OF glycogen synthesis (Glycogenesis)

1. Formation of the nucleotide sugar precursor.

All biochemical reactions involved in The formation of complex CARBOHYDRATES—oligo- and Polysaccharides—require metabolically active forms of Monosaccharides, which are sugar-nucleotide conjugates (see also below for the synthesis of Glycoproteins and Proteoglycans).

The metabolically active form of glucose used in the formation of unbranched homopolysaccharide chains of glycogen is UDP-glucose, which is formed in the following reaction.

The reaction is catalyzed by the enzyme UDP-glucose pyrophosphorylase and is reversible, but under physiological conditions, its equilibrium is shifted to the right due to the continuous Hydrolysis of the resulting pyrophosphate (H₄P₂O₇) by pyrophosphatase.

Glucose-1-phosphate, the substrate for this reaction, is formed from glucose-6-phosphate (see Chapter 11) through the action of phosphoglucomutase.

2. Formation of unbranched glycogen chains.

During the synthesis of α-1,4-glycosidic (amylose) glycogen chains, unbranched polysaccharide chains of pre-existing glycogen molecules in The Cell serve as acceptors for the activated glucose residues (“primer” glycogen). The enzyme UDP-glycogen transferase (glycogen synthase) transfers the monosaccharide moiety from UDP-glucose to the C-4 hydroxyl groups of the terminal (n-th) glucose residues:

3. Formation of branches in the glycogen molecule.

Branches in the glycogen molecule are formed via the intramolecular transfer of an oligosaccharide fragment consisting of 6-7 monomers from the end of a linear segment to the C-6 hydroxyl group of a glucose residue located several monosaccharide units away from the end of the molecule. The reaction is catalyzed by amylo-(1,4-1,6)-transglycosylase (branching enzyme).

According to this mechanism, glycogen macromolecules (m.w. 1·10⁶-2·10⁸) are synthesized, containing from several thousand to a million monosaccharide residues and forming granules 40-200 nm in size.

Fig. 13.1. Schematic representation of branch formation in the glycogen molecule.

Enzymatic reactions of glycogen degradation (Glycogenolysis).

1. The process of glycogenolysis proceeds via a phosphorolytic Cleavage mechanism, which involves the phosphorolysis of the 1,4-glycosidic bond at the non-reducing end of the glycogen molecule (the end containing a free (C-4)-OH group). This reaction releases glucose-1-phosphate, and the unbranched fragment of the glycogen molecule is shortened by one monosaccharide residue:

The enzyme catalyzing this reaction is Glycogen phosphorylase.

2. Phosphorylase cleaves monosaccharide residues in the form of glucose-1-phosphate from the straight amylose chains of glycogen. The cleavage of branched segments is carried out by amylo-1,6-glucosidase (the debranching enzyme).

The enzyme catalyzes glycosyltransferase and amylo-1,6-glucosidase reactions, specifically:

- it transfers an oligosaccharide residue consisting of three monosaccharides to the end of straight chains, which exposes glucose residues linked to the main chain via α(1→6)-glycosidic bonds;

- it hydrolytically cleaves (1→6)-glycosidic bonds, releasing free glucose molecules.

3. Glucose-1-phosphate, formed during glycogen phosphorolysis, is converted into glucose-6-phosphate by the action of phosphoglucomutase.

4. Subsequent Metabolic pathways of glucose-6-phosphate METABOLISM differ between liver and Muscle cells:

- in the liver, glucose-6-phosphate is converted by glucose-6-phosphatase into free glucose, which enters the bloodstream and is utilized by other organs and Tissues;

- in muscles, which lack glucose-6-phosphatase, glucose-6-phosphate is used to meet their own energy demands through aerobic or anaerobic oxidation.

The diagram of glycogen phosphorolysis in liver and muscle cells is shown in Fig. 13.2.

Fig. 13.2. Metabolic pathway of glycogen phosphorolysis in the liver and muscles.