Department of Cell Biology, University of Texas Southwestern Medical Center , Dallas, TX, USA.
Fly (Austin). 2020 Mar-Dec;14(1-4):3-9. doi: 10.1080/19336934.2020.1784674. Epub 2020 Jul 2.
Glutamine: fructose-6-phosphate amidotransferase (GFAT) enzymes catalyse the first committed step of the hexosamine biosynthesis pathway (HBP) using glutamine and fructose-6-phosphate to form glucosamine-6-phosphate (GlcN6P). Numerous species (e.g. mouse, rat, zebrafish, chicken) including humans and encode two broadly expressed copies of this enzyme but whether these perform redundant, partially overlapping or distinct functions is not known. To address this question, we produced single gene null mutations in the fly counterparts of and . Deletions for either enzyme were fully lethal and homozygotes lacking either GFAT1 or GFAT2 died at or prior to the first instar larval stage. Therefore, when genetically eliminated, neither isoform was able to compensate for the other. Importantly, dietary supplementation with D-glucosamine-6-phosphate rescued GFAT2 deficiency and restored viability to mutants. In contrast, glucosamine-6-phosphate did not rescue animals.
果糖-6-磷酸氨基转移酶（GFAT）酶使用谷氨酰胺和果糖-6-磷酸催化己糖生物合成途径（HBP）的第一步，形成葡萄糖胺-6-磷酸（GlcN6P）。许多物种（例如老鼠、老鼠、斑马鱼、鸡）包括人类和 编码这种酶的两个广泛表达的副本，但这些副本是否执行冗余、部分重叠或不同的功能尚不清楚。为了解决这个问题，我们在果蝇的对应物中产生了 和 的单基因缺失突变。对于任何一种酶的缺失都是完全致命的，并且缺乏 GFAT1 或 GFAT2 的纯合子在第一龄幼虫阶段或之前死亡。因此，当基因缺失时，两种同工酶都不能相互补偿。重要的是，D-葡萄糖胺-6-磷酸的饮食补充挽救了 GFAT2 缺陷，并恢复了 突变体的活力。相比之下，葡萄糖胺-6-磷酸不能拯救 动物。
