Schachter Harry
Program in Structural Biology and Biochemistry, Hospital for Sick Children, and Department of Biochemistry, University of Toronto, Ontario, Canada.
Biochim Biophys Acta. 2002 Dec 19;1573(3):292-300. doi: 10.1016/s0304-4165(02)00396-3.
The GlcNAc(beta)1,2Man(alpha)- moiety can be synthesized by at least two mammalian glycosyltransferases, UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I (GnT I, EC 2.4.1.101) and UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2). GnT I adds a GlcNAc residue in beta1,2 glycosidic linkage to the Man(alpha)1,3 arm of the N-glycan core to initiate the biosynthesis of hybrid and complex N-glycans. GnT I.2 can add GlcNAc in beta1,2 linkage to any alpha-linked terminal Man residue but has a strong preference for the Man(alpha)1-O-Thr- moiety which occurs in alpha-dystroglycan and other O-mannosylated glycoproteins. Mouse embryos lacking a functional GnT I gene (MgatI) were unable to synthesize complex N-glycans and none survived past 10.5 days after fertilization. The embryos showed multisystemic defects in various morphogenic processes such as neural tube formation, vascularization and the determination of left-right body plan asymmetry. Six human patients with muscle-eye-brain disease (MEB) were recently shown to have point mutations in the gene encoding GnT I.2 (MGATI.2). MEB is an autosomal recessive disease characterized by congenital muscular dystrophy, ocular abnormalities, brain malformations and other multisystemic defects. Both the MGATI.2 gene and MEB disease have been mapped to chromosome 1p32-p34. At least one of the biochemical sites affected by the MGATI.2 mutations is probably the interaction between laminin in the extracellular matrix and the peripheral membrane glycoprotein alpha-dystroglycan since this interaction is believed to require the presence of the sialyl(alpha)2,3Gal(beta)1,4GlcNAc(beta)1,2Man(alpha)1-O-Ser/Thr moiety on alpha-dystroglycan. It can be concluded that the GlcNAc(beta)1,2Man(alpha)- moiety is important for mammalian development due to an essential role in two distinct biochemical pathways.
GlcNAc(β)1,2Man(α)-部分可由至少两种哺乳动物糖基转移酶合成，即UDP-GlcNAc:α-3-D-甘露糖苷β1,2-N-乙酰葡糖胺基转移酶I（GnT I，EC 2.4.1.101）和UDP-GlcNAc:α-D-甘露糖苷β1,2-N-乙酰葡糖胺基转移酶I.2（GnT I.2）。GnT I将一个以β1,2糖苷键连接的GlcNAc残基添加到N-聚糖核心的Man(α)1,3臂上，以启动杂合型和复合型N-聚糖的生物合成。GnT I.2可以将β1,2连接的GlcNAc添加到任何α连接的末端Man残基上，但对存在于α-肌营养不良蛋白和其他O-甘露糖基化糖蛋白中的Man(α)1-O-Thr-部分有强烈偏好。缺乏功能性GnT I基因（MgatI）的小鼠胚胎无法合成复合型N-聚糖，且无一能在受精后10.5天存活。这些胚胎在各种形态发生过程中表现出多系统缺陷，如神经管形成、血管生成以及左右身体平面不对称的确定。最近发现，6例患有肌肉-眼-脑疾病（MEB）的人类患者在编码GnT I.2（MGATI.2）的基因中存在点突变。MEB是一种常染色体隐性疾病，其特征为先天性肌营养不良、眼部异常、脑畸形和其他多系统缺陷。MGATI.2基因和MEB疾病均已定位到1号染色体的p32-p34区域。MGATI.2突变影响的生化位点中至少有一个可能是细胞外基质中的层粘连蛋白与外周膜糖蛋白α-肌营养不良蛋白之间的相互作用，因为据信这种相互作用需要α-肌营养不良蛋白上存在唾液酸(α)2,3Gal(β)1,4GlcNAc(β)1,2Man(α)1-O-Ser/Thr部分。可以得出结论，由于GlcNAc(β)1,2Man(α)-部分在两条不同的生化途径中起重要作用，所以它对哺乳动物发育很重要。
