Reference : Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Endocrinology, metabolism & nutrition
Systems Biomedicine
Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency
Veiga-da-Cunha, Maria []
Chevalier, Nathalie []
Stephenne, Xavier []
Defour, Jean-Philippe []
Paczia, Nicole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Ferster, Alina []
Achouri, Younes []
Dewulf, Joseph P []
Linster, Carole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Bommer, Guido T []
Van Schaftingen, Emile []
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
Yes (verified by ORBilu)
Washington DC
[en] neutropenia ; SLGT2 inhibitors ; 1,5-anhydroglucitol ; metabolite repair ; glucose-6-phosphatase-β
[en] Neutropenia presents an important clinical problem in patients with G6PC3 or G6PT deficiency, yet why neutropenia occurs is unclear. We discovered that G6PC3 and G6PT collaborate to dephosphorylate a noncanonical metabolite (1,5anhydroglucitol-6-phosphate; 1,5AG6P) which is produced when glucose-phosphorylating enzymes erroneously act on 1,5-anhydroglucitol, a food-derived polyol present in blood. In patients or mice with G6PC3 or G6PT deficiency, 1,5AG6P accumulates and inhibits the first step of glycolysis. This is particularly detrimental in neutrophils, since their energy metabolism depends almost entirely on glycolysis. Consistent with our findings, we observed that treatment with a 1,5anhydroglucitol-lowering drug treats neutropenia in G6PC3deficient mice. Our findings highlight that the elimination of noncanonical side products by metabolite-repair enzymes makes an important contribution to mammalian physiology.
Researchers ; Students

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