Defective GFPT1 does not transfer an amino group from L-Gln to F6P to form GlcN6P

Glucosamine-fructose 6-phosphate aminotransferases 1 and 2 (GFPT1,2) are the first and rate-limiting enzymes in the hexosamine synthesis pathway, and thus formation of hexosamines like N-acetylglucosamine (GlcNAc). These enzymes probably play a role in limiting the availability of substrates for the N- and O-linked glycosylation of proteins. GFPT1 and 2 are required for normal functioning of neuromuscular synaptic transmission. Defects in GFPT1 cause myasthenia, congenital, with tubular aggregates 1 (CMSTA1; MIM:610542), characterised by altered muscle fibre morphology and impaired neuromuscular junction development (Senderek et al. 2011). The missense mutations observed do not always result in significant reduction in enzyme activity, but biopsies show reduced amounts of GFPT1 protein suggesting increased turnover or defective translation (Senderek et al. 2011). Example mutations are R111C, W240*, D348Y, T15A and T147Qfs*61 (Senderek et al. 2011).

葡萄糖胺-果糖-6-磷酸转氨酶1和2（GFPT1,2）是己糖胺合成途径中的首步且限速酶，因而参与N-乙酰葡萄糖胺（GlcNAc）等己糖胺的生成。这些酶可能在限制蛋白质N-和O-连接糖基化底物可用性方面发挥作用。GFPT1和2对于神经肌肉突触传递的正常功能是必需的。GFPT1的缺陷可导致先天性肌无力伴管状聚集物1（CMSTA1；MIM:610542），其特征为肌纤维形态改变和神经肌肉接头发育受损（Senderek等，2011年）。观察到的错义突变并不总是导致酶活性的显著降低，但活检显示GFPT1蛋白含量减少，这表明存在增加的周转或翻译缺陷（Senderek等，2011年）。示例突变包括R111C、W240*、D348Y、T15A和T147Qfs*61（Senderek等，2011年）。