Small molecule 3PO inhibits glycolysis but does not bind to 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (PFKFB3),FEBS Letters

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Small molecule 3PO inhibits glycolysis but does not bind to 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (PFKFB3)
FEBS Letters ( IF 3.0 ) Pub Date : 2020-07-20 , DOI: 10.1002/1873-3468.13878
Besa Emini Veseli ₁ , Paola Perrotta ₁ , Pieter Van Wielendaele ₂ , Anne-Marie Lambeir ₂ , Anahita Abdali ₃ , Stefano Bellosta ₃ , Giovanni Monaco _{4,

5} , Geert Bultynck ₄ , Wim Martinet ₁ , Guido R Y De Meyer ₁

Affiliation

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 µm, in contrast to 3 µm 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.

中文翻译：

小分子 3PO 抑制糖酵解但不与 6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶-3 (PFKFB3) 结合

6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶异构体3（PFKFB3）是糖酵解途径的关键酶，在血管生成中起重要作用。3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) 经常用作糖酵解抑制剂，被认为可以抑制 PFKFB3。然而，3PO 的后一种影响从未被详细研究过，这是本研究的目的。为了证明 3PO 与 PFKFB3 的结合，我们使用了等温滴定量热法。然而，3PO 不与 PFKFB3 结合，甚至高达 750 µm，与 AZ67 的 3 µm 形成对比，AZ67 是一种有效且特异的 PFKFB3 抑制剂。相反，3PO 在细胞内积累乳酸，导致细胞内 pH 值降低并抑制糖酵解途径的酶促反应。

更新日期：2020-07-20

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