Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
– As a rate-limiting enzyme in glycolysis, PFK1 is subject to complex regulation through allosteric effectors including ATP, AMP, and fructose-2,6-bisphosphate.
• Metabolic Control:
–PFK1 activity is central to controlling the pace of glycolysis, thereby influencing energy production and intermediary metabolite supply.
– In highly proliferative cells or cells under growth conditions, increased glycolytic flux (and, by extension, PFK1 activity) supports the biosynthetic demands of cell division.
– Many tumors (including breast, colorectal, and lung cancers) have been reported to have increased PFK1 expression/activity relative to normal tissues.
– High glycolytic flux, driven partly by enhanced PFK1, supports rapid cell proliferation and survival in the nutrient/stress-challenged tumor microenvironment.
Inhibitors:(typically glycolysis is targeted more broadly)
-Citrate
-Hydrogen ions (pH) – Acidic conditions can have inhibitory effects.
-3PO: inhibits PFKFB3, thereby indirectly reducing PFK1 activity.
-Resveratrol can downregulate glycolytic flux in cancer cells, which may indirectly affect PFK1 activity.
- FMDs offer an indirect strategy to modulate cancer metabolism by broadly reducing glycolysis. Their impact on PFK1 is likely part of a complex network of metabolic adaptations rather than a direct inhibitory effect.
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