FBP2 Active Protein

FBPase 2: a key enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate, a precursor to glucose 6-phosphate. A regulator of glucose synthesis from non-carbohydrates. Two paralogs of this enzyme exists in humans: FBP1 is expressed in the liver and gluconeogenic tissues, and FBP2 in striated muscle. FBP2 is only isozyme expressed in striated muscle and it is widely expressed in cells that are nongluconeogenic. Both forms are inhibited allosterically by AMP, NAD and Ca2+. The muscle form is about 100-fold more sensitive to AMP and NAD, and about 1000-fold more sensitive to inhibition by Ca2+, the major activator of glycolysis in striated muscle. Forms an active complex with aldolase that binds to the sarcomeric Z-line, which is disrupted by elevated calcium levels, blocking glycogen synthesis during exercise. Forms homotetramers that are stabilized in the active state by divalent cations (Mg2+, Mn2+ , Co+2, or Zn2+). Its interaction with aldolase appears to desensitizes it to inhibition by AMP and, partially, by Ca2+. Up to 50% of lactate generated in striated muscle is converted to glycogen.

Protein type: Carbohydrate Metabolism - fructose and mannose; EC 3.1.3.11; Carbohydrate Metabolism - glycolysis and gluconeogenesis; Carbohydrate Metabolism - pentose phosphate pathway; Phosphatase (non-protein)

Chromosomal Location of Human Ortholog: 9q22.3

Cellular Component: cytosol; nucleus; cell junction; Z disc

Molecular Function: metal ion binding; fructose-bisphosphatase activity

Biological Process: dephosphorylation; carbohydrate metabolic process; glucose metabolic process; pathogenesis; fructose metabolic process; gluconeogenesis