Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review

作者：Caiting Yang, Fuxiang Chu, Xiaoli Chen, Fanqi Meng, Yinhao Li, Jingwen Chen, Chaoyang Sun, Yahui Shang, Ruibin Guo, Jian Ming Wang, Changxin Wu, Hepeng Duan, Miaomiao Shao, Wei Yuan · 发表于：Cell Death Discovery · 年份：2025 · DOI：10.1038/s41420-025-02898-8 · 被引用次数：2 · 研究领域：Diet, Metabolism, and Disease、Glycosylation and Glycoproteins Research、Cancer, Hypoxia, and Metabolism

Glutamine: fructose-6-phosphate amidotransferase (GFAT), a conserved enzyme across prokaryotic and eukaryotic species, is the first and rate-limiting step in the hexosamine biosynthetic pathway (HBP), diverting 2-5% of fructose-6-phosphate derived from glucose toward the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a key substrate for the glycosylation of proteins and lipids. While substantial progress has been made in elucidating the basic biochemical properties and regulatory mechanisms of GFAT, its functional impact on pathological processes remains incompletely understood. Emerging evidence implicates GFAT in a spectrum of human diseases, including cancer, diabetes, cardiovascular disorders, and neurodegenerative conditions such as Alzheimer's disease. This review aims to provide a comprehensive synthesis of current insights into GFAT's role in disease etiology, with the goal of informing future research and therapeutic strategies targeting this essential metabolic regulator.