fructose16bisfosfatase

Fructose-1,6-bisphosphatase, often abbreviated FBPase, is a cytosolic enzyme that catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate. It plays a central role in gluconeogenesis, providing a bypass for the irreversible phosphofructokinase-1 step of glycolysis and enabling the generation of glucose from non-carbohydrate sources.

In humans, the major form is cytosolic FBPase 1 (FBP1), encoded by the FBP1 gene. It is predominantly expressed in liver and kidney, tissues where gluconeogenesis is active. Some organisms express additional tissue- or species-specific isozymes, reflecting variations in metabolic regulation.

Regulation of FBPase is primarily allosteric. The enzyme is inhibited by AMP and by fructose-2,6-bisphosphate, a potent regulator of glycolysis and gluconeogenesis. Hormonal signals that lower hepatic fructose-2,6-bisphosphate levels, such as glucagon through cAMP-dependent pathways, favor FBPase activity and gluconeogenesis, helping to raise blood glucose during fasting.

Clinical significance includes hereditary fructose-1,6-bisphosphatase deficiency, a rare autosomal recessive metabolic disorder. Affected individuals may experience fasting hypoglycemia, lactic acidosis, ketosis, and other metabolic disturbances, particularly after fasting or illness. Diagnosis involves biochemical testing and genetic sequencing, and treatment centers on avoiding prolonged fasting and ensuring energy and carbohydrate intake to prevent hypoglycemia.

See also: gluconeogenesis, phosphofructokinase-1, fructose-2,6-bisphosphate.