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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月14日

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  • Caiting Yang,
  • Fengyu Chu,
  • Xiaoli Chen,
  • Fanqi Meng,
  • Yinhao Li,
  • Jingwen Chen,
  • Chaoyang Sun,
  • Yahui Shang,
  • Ruibin Guo,
  • Jianming Wang,
  • Changxin Wu,
  • Huiping Duan,
  • Miaomiao Shao,
  • Wei Yuan

摘要

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.