Fructose-1,6-bisphosphatase 2 (FBP2)

Fructose-1,6-bisphosphatase 2 (FBP2) is a key metabolic enzyme that primarily catalyzes the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate during gluconeogenesis, fundamental for glucose production in muscle and other tissues. Beyond its conventional metabolic role, FBP2 regulates mitochondrial function, protects mitochondria from calcium-induced stress, and acts in cell cycle progression, especially in cardiomyocytes and muscle. FBP2 is also implicated in tumor suppression; loss of FBP2 facilitates glycolytic reprogramming (Warburg effect), while re-expression curbs cancer cell growth by activating AMPK, suppressing Akt-mTOR pathways, and modulating mitochondrial biogenesis. In the nervous system, FBP2 supports synaptic plasticity and memory formation by interacting with neuronal mitochondria and calcium signaling pathways. The enzyme exists in dimeric and tetrameric states, which differentially influence both its metabolic and non-metabolic functions, and is allosterically inhibited by AMP. FBP2’s moonlighting effects exemplify its tissue-specific, context-dependent functionality, positioning it as a multi-faceted therapeutic target in oncology, metabolic, cardiac, and neurodegenerative diseases.

Other names

Fructose-1,6-bisphosphatase isozyme 2FBP2FBPase 2D-fructose-1,6-bisphosphate 1-phosphohydrolase 2Muscle FBPaseCORLKHexosediphosphataseMuscle fructose-bisphosphatase

Allosteric inhibition (AMP binds and shifts oligomeric state to inactive form); Direct enzyme inhibition (Blocks the hydrolysis of fructose 1,6-bisphosphate, limiting gluconeogenesis); Restoration of FBP2 expression or activity (in cancer, re-expression inhibits glycolysis and promotes apoptosis)