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

Stephan Hinderlich; Ilan Salama; Iris Eisenberg; Tamara Potikha; Lars R Mantey; Kevin J Yarema; Rüdiger Horstkorte; Zohar Argov; Menachem Sadeh; Werner Reutter; Stella Mitrani-Rosenbaum

doi:10.1016/j.febslet.2004.04.013

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

FEBS Lett. 2004 May 21;566(1-3):105-9. doi: 10.1016/j.febslet.2004.04.013.

Authors

Stephan Hinderlich¹, Ilan Salama, Iris Eisenberg, Tamara Potikha, Lars R Mantey, Kevin J Yarema, Rüdiger Horstkorte, Zohar Argov, Menachem Sadeh, Werner Reutter, Stella Mitrani-Rosenbaum

Affiliation

¹ Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Institut für Biochemie und Molekularbiologie, Arnimallee 22, 14195 Berlin-Dahlem, Germany. stephan.hinderlich@charite.de

PMID: 15147877
DOI: 10.1016/j.febslet.2004.04.013

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Animals
B-Lymphocytes / enzymology
Carbohydrate Epimerases / genetics*
Carbohydrate Epimerases / metabolism*
Cell Line
Cell Membrane / metabolism
Cytosol / enzymology
Escherichia coli Proteins / genetics
Escherichia coli Proteins / metabolism
Flow Cytometry
Homozygote
Humans
Myositis, Inclusion Body / enzymology
Myositis, Inclusion Body / metabolism*
N-Acetylneuraminic Acid / metabolism*
Phosphotransferases (Alcohol Group Acceptor) / genetics*
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Spodoptera / cytology
Tumor Cells, Cultured

Substances

Escherichia coli Proteins
Recombinant Proteins
Phosphotransferases (Alcohol Group Acceptor)
N-acylmannosamine kinase
Carbohydrate Epimerases
UDP acetylglucosamine-2-epimerase
N-Acetylneuraminic Acid