Brinkman-Van der Linden E C, Mollicone R, Oriol R, Larson G, Van den Eijnden D H, Van Dijk W
Department of Medical Chemistry, Faculty of Medicine, Van der Boechorststraat 7, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
J Biol Chem. 1996 Jun 14;271(24):14492-5. doi: 10.1074/jbc.271.24.14492.
The major alpha3-fucosyltransferase activity in human plasma is encoded by the gene for fucosyltransferase VI (FUT6). A missense mutation (Gly-739 --> Ala) in this gene is responsible for deficiency of enzyme activity in plasma. To examine whether this fucosyltransferase is the sole enzyme responsible for the alpha3-fucosylation of serum glycoproteins in the liver, we studied the fucosylation of three glycoproteins in sera of individuals with or without inactivated FUT3 and/or FUT6 gene(s) but with a functional FUT5 gene. alpha1-Acid glycoprotein was used as the principal reporter protein for liver alpha3-fucosyltransferase activity, because of its high fucose content. In all individuals with the FUT6 missense mutation Gly-739 --> Ala in double dose, no fucosylation of alpha1-acid glycoprotein was found. This alpha1-acid glycoprotein was not intrinsically resistant to fucosylation, since it was susceptible to in vitro fucosylation using an alpha3/4-fucosyltransferase isolated from human milk. The same result was found for alpha1-antichymotrypsin and alpha1-protease inhibitor. On the other hand in all individuals with alpha3-fucosyltransferase activity in plasma, alpha3-fucosylated glycoforms of the glycoproteins studied were found. The degree of fucosylation of alpha1-acid glycoprotein was correlated with alpha3-fucosyltransferase activity (Rs = 0.82). These data indicate that the product of FUT6, but not of FUT3 or of FUT5, is responsible for the alpha3-fucosylation of glycoproteins produced in liver and suggest that this organ is a major source of alpha3-fucosyltransferase activity in plasma.
人血浆中的主要α3-岩藻糖基转移酶活性由岩藻糖基转移酶VI（FUT6）基因编码。该基因中的一个错义突变（Gly-739→Ala）导致血浆中酶活性缺乏。为了研究这种岩藻糖基转移酶是否是肝脏中血清糖蛋白α3-岩藻糖基化的唯一负责酶，我们研究了FUT3和/或FUT6基因失活但FUT5基因功能正常的个体血清中三种糖蛋白的岩藻糖基化情况。α1-酸性糖蛋白因其高岩藻糖含量，被用作肝脏α3-岩藻糖基转移酶活性的主要报告蛋白。在所有双剂量携带FUT6错义突变Gly-739→Ala的个体中，未发现α1-酸性糖蛋白的岩藻糖基化。这种α1-酸性糖蛋白并非本质上对岩藻糖基化有抗性，因为它对使用从人乳中分离的α3/4-岩藻糖基转移酶进行的体外岩藻糖基化敏感。α1-抗糜蛋白酶和α1-蛋白酶抑制剂也得到了相同的结果。另一方面，在所有血浆中具有α3-岩藻糖基转移酶活性的个体中，发现了所研究糖蛋白的α3-岩藻糖基化糖型。α1-酸性糖蛋白的岩藻糖基化程度与α3-岩藻糖基转移酶活性相关（Rs = 0.82）。这些数据表明，FUT6而非FUT3或FUT5的产物负责肝脏中产生的糖蛋白的α3-岩藻糖基化，并表明该器官是血浆中α3-岩藻糖基转移酶活性的主要来源。
