FBPase1

Fructose-1,6-bisphosphatase 1 (FBPase-1) is a cytosolic enzyme that catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate, a rate-limiting step in gluconeogenesis and a key control point opposing glycolysis. In humans, it is encoded by the FBP1 gene.

FBPase-1 is predominantly expressed in liver and kidney tissues, where it participates in glucose production during fasting. The enzyme is regulated by metabolite levels and hormonal signals: it is inhibited allosterically by AMP and fructose-2,6-bisphosphate, and activated by citrate. Hormonal regulation involves transcriptional control through glucagon and epinephrine signaling, which raise FBP1 expression, while insulin tends to suppress it.

Genetic mutations in FBP1 can cause fructose-1,6-bisphosphatase deficiency, an autosomal recessive metabolic disorder. Patients may present with fasting hypoglycemia, metabolic acidosis, ketosis, and lactate elevation, often in infancy or early childhood. Diagnosis relies on biochemical findings and confirmed FBP1 variants; management emphasizes avoiding prolonged fasting and managing metabolic crises.

Biochemically, FBPase-1 belongs to the class I fructose-1,6-bisphosphatase family and requires divalent cations for activity. Its action complements phosphofructokinase-1, helping direct carbon flux toward glucose production rather than glycolysis under gluconeogenic conditions.