title: The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy.
abstract: Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single homozygous mutation occurs, converting methionine-712 to threonine. Recombinant expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine kinase activity, in agreement with the localization of the mutation within the kinase domain. B lymphoblastoid cell lines derived from patients expressing the mutated enzyme also display reduced UDP-N-acetylglucosamine 2-epimerase activity. Nevertheless, no reduced cellular sialylation was found in those cells by colorimetric assays and lectin analysis, indicating that HIBM is not directly caused by an altered overall expression of sialic acids.
authors.affiliation: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Institut für Biochemie und Molekularbiologie, Arnimallee 22, 14195 Berlin-Dahlem, Germany. stephan.hinderlich@charite.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Hinderlich
authors.forename: Ilan
authors.initials: I
authors.lastname: Salama
authors.forename: Iris
authors.initials: I
authors.lastname: Eisenberg
authors.forename: Tamara
authors.initials: T
authors.lastname: Potikha
authors.forename: Lars R
authors.initials: LR
authors.lastname: Mantey
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yarema
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
authors.forename: Stella
authors.initials: S
authors.lastname: Mitrani-Rosenbaum
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D002238:Carbohydrate Epimerases / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006720:Homozygote; D006801:Humans; D018979:Myositis, Inclusion Body / Q000201:enzymology / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology; D014407:Tumor Cells, Cultured
chemical_list: D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; D019158:N-Acetylneuraminic Acid