Bork Kaya, Reutter Werner, Gerardy-Schahn Rita, Horstkorte Rüdiger
Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
FEBS Lett. 2005 Sep 12;579(22):5079-83. doi: 10.1016/j.febslet.2005.08.013.
Sialic acids are expressed as terminal sugars in many glycoconjugates and play an important role during development and regeneration, as they are involved as polysialic acid in a variety of cell-cell interactions mediated by the neural cell adhesion molecule NCAM. The key enzyme for the biosynthesis of sialic acid is the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE). Mutations in the binding site of the feedback inhibitor CMP-sialic acid of the GNE leads to sialuria, a disease in which patients produce sialic acid in gram scale. Here, we report on the consequences after expression of a sialuria-mutated GNE. Expression of the sialuria-mutated GNE leads to a dramatic increase of both cellular sialic acid and polysialic acid on NCAM. This could also be achieved by application of the sialic acid precursor N-acetylmannosamine. Our data suggest that biosynthesis of sialic acid regulates and limits the synthesis of polysialic acid.
唾液酸在许多糖缀合物中作为末端糖表达，并且在发育和再生过程中发挥重要作用，因为它们作为多唾液酸参与由神经细胞粘附分子NCAM介导的多种细胞间相互作用。唾液酸生物合成的关键酶是UDP-N-乙酰葡糖胺2-表异构酶/N-乙酰甘露糖胺激酶（GNE）。GNE的反馈抑制剂CMP-唾液酸结合位点的突变导致唾液酸尿症，即患者以克级产生唾液酸的一种疾病。在此，我们报告了唾液酸尿症突变型GNE表达后的后果。唾液酸尿症突变型GNE的表达导致细胞唾液酸和NCAM上的多唾液酸都显著增加。这也可以通过应用唾液酸前体N-乙酰甘露糖胺来实现。我们的数据表明，唾液酸的生物合成调节并限制了多唾液酸的合成。
