Glycogen metabolism

Glycogen metabolism

The metabolic path for Glycogen starts with alfa-D-Glucose that is phosphorylated by a set of enzymes: Hexokinase 1 (HXK1) [1], [2], [3], Hexokinase 2 (HXK2) [4], [5], [6], Hexokinase 3 (HXK3) [6], [7], [8], Glucokinase (hexokinase 4) (HXK4) [9], [10], [11], [12], [13] and alpha-(D)-Glucose-6-phosphate is formed. Also, alpha-D-Glucose is isomerically transformed into beta-D-Glucose by Galactose mutarotase (aldose 1-epimerase) (GALM) [14], [15], [16]. Beta-D-Glucose undergoes the same transformations that alpha-D-glucose under the action of the same enzymes to form beta-(D)-Glucose-6-phosphate which subsequently takes another stereoisomerisation step to alpha-(D)-Glucose-6-phosphate. This step is catalyzed by Glucose phosphate isomerase (GPI) [17]. Phosphoglucomutase 1 (PGMU) catalyzes the next isomerization of alpha-(D)-Glucose-6-phosphate leading to formation of alpha-(D)-Glucose 1-phosphate [18], [19]. UDP is then attached to alpha-(D)-Glucose 1-phosphate by UDP-glucose pyrophosphorylase 1 (UGPA1) or UDP-glucose pyrophosphorylase 2 (UGPA2) to form UDP-D-glucose [20], [21], [22], [23].

UDP-D-glucose polymerizes with (alpha-D-glucosyl-(1-4))n to form Glycogen. This step is catalyzed by Glucan (1,4-alpha-), branching enzyme 1 (GLGB) [24], [25], [26], [27]. On the other hand, Glycogen synthase 1 (muscle) (GYS1) and Glycogen synthase 2 (liver) (GYS2) can cleave UDP-D-glucose from Glycogen to release (alpha-D-glucosyl-(1-4))n [28], [29], [30], [31], [32]. A number of glycogen phosphorylases (Phosphorylase, glycogen, liver (PYGL), Phosphorylase, glycogen, brain (PYGB) and Phosphorylase, glycogen, muscle (PYGM)) mediate phosphorolysis of Glycogen, which is regarded as transfer of one sugar residue (alpha-D-glucose 1-phosphate) from Glycogen to inorganic phosphate. As a result Glycogen chain decreased for one sugar moiety with formation of a reduced product (alpha-D-glucosyl-(1-4))(,n=3)-alpha-D-glucosyl-(1-6)*(glycogen). [33], [34], [35], [36], [37], [38]. This product is a substrate for Amylo-1, 6-glucosidase, 4-alpha-glucanotransferase - glycogen debranching enzyme (GDE) that fractionates the polymeric structure to form two metabolites: the main chain - alpha-D-glucosyl-(1-6)*(glycogen) and branch chain of Glycogen - (alpha-D-glucosyl-(1-4))(,n=3) [39], [40], [41], [42], [43]. GDE also affects both products of the latter reaction. Alpha-D-glucosyl-(1-4))(,n=3) can be directly repolymerized to Glycogen; alpha-D-glucosyl-(1-6)*(glycogen) can be further hydrolyzed giving alpha-D-Glucose as a product.[40], [41], [43].

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