Fructose metabolism and fructose kinase KHK–C/A are key factors in the development of lipid oversynthesis-promoted metabolic disorders and cancer. Here, we summarize and discuss the current knowledge about the specific features of fructose metabolism and the distinct roles of KHK–C and KHK–A in metabolic liver diseases and their relevant metabolic disorders and cancer, and we highlight the specific protein kinase activity of KHK–A in tumor development. In addition, different approaches that have been used to inhibit KHK and the exploration of KHK inhibitors in clinical treatment are introduced.
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