Glycogen metabolism (Homo sapiens)
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Description
Glycogen, a highly branched glucose polymer, is formed and broken down in most human tissues, but is most abundant in liver and muscle, where it serves as a major stored fuel. Glycogen metabolism has been studied in most detail in liver and skeletal muscle. Glycogen metabolism in other tissues has not been studied as extensively, and is thought to resemble the muscle process.
Glycogen synthesis involves five reactions. The first two, conversion of glucose 6-phosphate to glucose 1-phosphate and synthesis of UDP-glucose from glucose 1-phosphate and UTP, are shared with several other pathways. The next three reactions, the auto-catalyzed synthesis of a glucose oligomer on glycogenin, the linear extension of the glucose oligomer catalyzed by glycogen synthase, and the formation of branches catalyzed by glycogen branching enzyme, are unique to glycogen synthesis. Repetition of the last two reactions generates large, extensively branched glycogen polymers. The catalysis of glycogenin glucosylation and oligoglucose chain extension by distinct isozymes in liver and nonhepatic tissues allows them to be regulated independently (Agius 2008; Bollen et al. 1998; Roach et al. 2012).
Cytosolic glycogen breakdown occurs via the same chemical steps in all tissues but is separately regulated via tissue specific isozymes and signaling pathways that enable distinct physiological fates for glycogen in liver and other tissues. Glycogen phosphorylase, which can be activated by phosphorylase kinase, catalyzes the removal of glucose residues as glucose 1-phosphate from the ends of glycogen branches. The final four residues of each branch are removed in two steps catalyzed by debranching enzyme, and further glycogen phosphorylase activity completes the process of glycogen breakdown. The first glucose residue in each branch is released as free glucose; all other residues are released as glucose 1-phosphate. The latter molecule can be converted to glucose 6-phosphate in a step shared with other pathways (Villar-Palasi & Larner 1970; Hers 1976).
Glycogen can also be taken up into lysosomes, where it is normally broken done by the action of a single enzyme, lysosomal alpha-glucosidase (GAA) (Brown et al. 1970). View original pathway at:Reactome.
Glycogen synthesis involves five reactions. The first two, conversion of glucose 6-phosphate to glucose 1-phosphate and synthesis of UDP-glucose from glucose 1-phosphate and UTP, are shared with several other pathways. The next three reactions, the auto-catalyzed synthesis of a glucose oligomer on glycogenin, the linear extension of the glucose oligomer catalyzed by glycogen synthase, and the formation of branches catalyzed by glycogen branching enzyme, are unique to glycogen synthesis. Repetition of the last two reactions generates large, extensively branched glycogen polymers. The catalysis of glycogenin glucosylation and oligoglucose chain extension by distinct isozymes in liver and nonhepatic tissues allows them to be regulated independently (Agius 2008; Bollen et al. 1998; Roach et al. 2012).
Cytosolic glycogen breakdown occurs via the same chemical steps in all tissues but is separately regulated via tissue specific isozymes and signaling pathways that enable distinct physiological fates for glycogen in liver and other tissues. Glycogen phosphorylase, which can be activated by phosphorylase kinase, catalyzes the removal of glucose residues as glucose 1-phosphate from the ends of glycogen branches. The final four residues of each branch are removed in two steps catalyzed by debranching enzyme, and further glycogen phosphorylase activity completes the process of glycogen breakdown. The first glucose residue in each branch is released as free glucose; all other residues are released as glucose 1-phosphate. The latter molecule can be converted to glucose 6-phosphate in a step shared with other pathways (Villar-Palasi & Larner 1970; Hers 1976).
Glycogen can also be taken up into lysosomes, where it is normally broken done by the action of a single enzyme, lysosomal alpha-glucosidase (GAA) (Brown et al. 1970). View original pathway at:Reactome.
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dextrin-glycogenin
dimerAnnotated Interactions
While initial studies of PGYM from rabbit muscle suggested that it is a homotetramer (Keller and Cori 1953), more recent work indicates that under physiological conditions the enzyme occurs as a homodimer (Huang and Graves 1970) and a dimeric structure for the human enzyme is inferred here.
While initial studies of glycogen phosphorylase PGYM from rabbit muscle suggested that it is a homotetramer (Keller and Cori 1953), more recent work indicates that under physiological conditions the enzyme occurs as a homodimer (Huang and Graves 1970) and a dimeric structure for human PYGL enzyme is inferred here.
This reaction takes place in the 'cytoplasm' and is mediated by the 'amylo-alpha-1,6-glucosidase activity' of 'glycogen debranching enzyme'.
dextrin-glycogenin
dimer