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Small molecule 3PO inhibits glycolysis but does not bind to 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (PFKFB3)
Author(s) -
Emini Veseli Besa,
Perrotta Paola,
Van Wielendaele Pieter,
Lambeir AnneMarie,
Abdali Anahita,
Bellosta Stefano,
Monaco Giovanni,
Bultynck Geert,
Martinet Wim,
De Meyer Guido R. Y.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13878
Subject(s) - chemistry , glycolysis , isothermal titration calorimetry , biochemistry , gene isoform , enzyme , intracellular , biophysics , biology , gene
6‐Phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) is a key enzyme of the glycolytic pathway, and it plays an essential role in angiogenesis. 3‐(3‐Pyridinyl)‐1‐(4‐pyridinyl)‐2‐propen‐1‐one (3PO) is frequently used as a glycolysis inhibitor and is thought to inhibit PFKFB3. However, this latter effect of 3PO has never been investigated in detail and was the aim of the present study. To demonstrate binding of 3PO to PFKFB3, we used isothermal titration calorimetry. However, 3PO did not bind to PFKFB3, even up to 750 µ m , in contrast to 3 µ m of AZ67, which is a potent and specific PFKFB3 inhibitor. Instead, 3PO accumulated lactic acid inside the cells, leading to a decrease in the intracellular pH and an inhibition of enzymatic reactions of the glycolytic pathway.