The glycogenin is a protein whose main function is to be the initiator molecule of glycogen synthesis (glycogenesis), a process that allows the storage of glucose residues in the form of a polysaccharide. Glucose residues are added to glycogenin through α-1,4 bonds. The first step in the glycogen synthesis is indeed the synthesis of this protein. Each glycogen molecule is linked to a glycogenin by a glycosidic linkage which involves the first glucose residue of the chain and a tyrosine residue of glycogenin. The glycogenin designation stems from the fact that this protein is involved in the genesis of glycogen, by functioning as a primer in the formation of a new glycogen molecule.The glycogenin through its glucosyltransferase activity, binds covalently to itself a glucose molecule (from UDP-glucose - the active form of glucose). Then, the glycogenin forms a compact complex with glycogen synthase, the enzyme responsible for glycogen synthesis. After the addition of up to 7 more glucose residues (from UDP-glucose) mediated again by the activity of glucosyltransferase of glycogenin. Finally, glycogen synthase and branching enzyme enter in action, being glycogenin covalently linked to the unique reducing end of the glycogen molecule.In humans there are two isoforms of glycogenin which can be expressed as glycogenin-1, having a molecular weight of 37 kD, and encoded by the GYG gene that is expressed mainly in muscle, or as glycogenin-2 having a molecular weight of 66 kDae encoded by GYG2 gene which is expressed mainly in the liver, cardiac muscle and other types of tissues except skeletal muscle
Disability glycogenin-1 (GYG1) - Mutation of the gene GYG1
A glycogenin-1 deficiency was detected in its gene, GYG1, which revealed a nonsense mutation in one allele and a missense mutation in another allele. A missense mutation results from inactivation of the autoglycosilation of glycogenin-1, which is required for the initiation of glycogen synthesis in muscle. The glycogenin-1 autoglycosilation occurs at Tyr195 by the action of glucose-1-O-tyrosine. A missense mutation of this residue results in inactivation of the autoglycosilation. However, it was also demonstrated that missense mutations affecting other residues of glycogenin 1-cause problems on autoglycosilation.
Phenotypic characteristics of skeletal muscle in a patient with this disorder are muscle glycogen depletion, mitochondrial proliferation and marked predominance of slow twitch amd oxidized muscle fibers. Mutations in glycogenin-1 gene GYG1 are also causes of cardiomyopathy and arrhythmia.
A glycogenin-1 deficiency was detected in its gene, GYG1, which revealed a nonsense mutation in one allele and a missense mutation in another allele. A missense mutation results from inactivation of the autoglycosilation of glycogenin-1, which is required for the initiation of glycogen synthesis in muscle. The glycogenin-1 autoglycosilation occurs at Tyr195 by the action of glucose-1-O-tyrosine. A missense mutation of this residue results in inactivation of the autoglycosilation. However, it was also demonstrated that missense mutations affecting other residues of glycogenin 1-cause problems on autoglycosilation.
Phenotypic characteristics of skeletal muscle in a patient with this disorder are muscle glycogen depletion, mitochondrial proliferation and marked predominance of slow twitch amd oxidized muscle fibers. Mutations in glycogenin-1 gene GYG1 are also causes of cardiomyopathy and arrhythmia.
Text written by:
Daniela Marinheiro
Carla Marty
Maria Rocha
Marta Rodrigues
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