Disease relevance of Fbp2

• In rat hepatoma (HTC) cells, this enzyme has kinetic, antigenic, and regulatory properties, such as insensitivity to cyclic AMP-dependent protein kinase and lack of associated FBPase-2 activity, that differ from those in liver [1].
• An N-terminally truncated recombinant peptide of 380 residues containing the PFK-2 and FBPase-2 domains was expressed in Escherichia coli as a beta-galactosidase fusion protein [1].

High impact information on Fbp2

• The control of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2; EC 2.7.1.105/3.1.3.46) gene expression during liver regeneration was studied [2].
• Interaction of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) with glucokinase activates glucose phosphorylation and glucose metabolism in insulin-producing cells [3].
• The properties of these recombinant proteins were compared with those of the PFK-2/FBPase-2 present in rat skeletal muscle and liver [4].
• The PFK-2/FBPase-2 mRNA in fetal hepatocytes was more stable than in the adult cells [5].
• Dexamethasone also increased the PFK-2/FBPase-2 mRNA levels and costimulation of fetal hepatocytes with dexamethasone and a permeant analogue of cyclic AMP enhanced the levels of PFK-2/FBPase-2 mRNA, a situation opposite to that exhibited by adult hepatocytes [5].

Chemical compound and disease context of Fbp2

• The results indicate that in established lines of hepatoma cells the biochemical properties of the bifunctional enzyme, PFK-2/FBPase-2, involved in the synthesis and degradation of fructose 2,6-bisphosphate, differ from those of the enzyme from normal liver [6].

Biological context of Fbp2

• Only in cells overexpressing the wild-type liver PFK-2/FBPase-2 isoform was the increase of GK activity abolished by forskolin, apparently due to the regulatory site for phosphorylation by a cAMP-dependent protein kinase [3].
• The mutation also increased the Vmax. of FBPase-2 4-fold without changing the Km for Fru-2,6-P2 or IC50 of Fru-6-P [7].
• In liver, the 470-residue bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) catalyses the synthesis and degradation of fructose 2,6-bisphosphate, a potent stimulator of glycolysis [1].
• These data, together with immunoblot experiments, suggest that the lack of associated FBPase-2 activity in HTC cells results from a post-translational modification of the enzyme rather than from the difference in amino acid sequence [1].
• Three distinct clones encoding full-length 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBPase-2) were characterized from a rat liver cDNA library [8].

Anatomical context of Fbp2

• The aim of this work was to identify the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) isozyme(s) present in white adipose tissue [9].
• Characterization of the PFK-2/FBPase-2 mRNAs showed that mature adipocytes express the mRNA that codes for the L isozyme and the two mRNAs that code for the M isozyme [9].
• The levels of brain PFK-2/FBPase-2 gene expression as well as the enzymatic activity and the concentration of Fru-2,6-P(2) appear to be remarkably constant during adult life, without significant differences in the brain hippocampus, cortex, cerebellum or striatum areas [10].

Associations of Fbp2 with chemical compounds

• This cDNA predicts a protein of 448 residues in which the first 32 residues of liver PFK-2/FBPase-2 including the cyclic AMP target sequence have been replaced by a unique N-terminal decapeptide [1].
• In recombinant rat muscle PFK-2/FBPase-2, mutation of Arg-104 to Ser increased the Km for Fru-6-P 60-fold, increased the IC50 of citrate, increased the Vmax [7].
• In recombinant rat liver PFK-2/FBPase-2, mutation of Arg-225 to Ser increased the Km of PFK-2 for fructose-6-phosphate (Fru-6-P) 7-fold at pH 6 and decreased PFK-2 activity at suboptimal substrate concentrations between pH 6 and 9 [7].
• The kinetics of PFK-2 and FBPase-2 from rat liver were investigated with respect to the substrates and the effector sn-glycerol 3-phosphate [11].
• The dynamics of the PFK-2/FBPase-2 cycle has been investigated in an enzyme system composed of PFK-2/FBPase-2, creatine kinase and creatine phosphate. sn-Glycerol 3-phosphate was found to decrease the quasi-stationary concentration of Fru 2,6-P2 [11].

Analytical, diagnostic and therapeutic context of Fbp2

• No alteration in the degradation rate of PFK-2/FBPase-2 mRNA was noted after partial hepatectomy [2].
• The time course of mRNA modulation was well correlated with PFK-2/FBPase-2 activity and with the amount of bifunctional enzyme protein determined by immunoblotting with an antibody raised against the N-terminal decapeptide of liver PFK-2/FBPase-2 [2].
• The roles of Arg-104 and Arg-225 located in the 2-kinase domain of the bifunctional enzyme 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBPase-2) have been studied by site-directed mutagenesis [7].
• Dot and Northern blots showed signals indicative of three distinct PFK-2/FBPase-2 mRNAs [8].
• Northern blot and RT-PCR analysis demonstrated that ubiquitous PFK-2/FBPase-2 is expressed in rat brain from embryonic to adult life and shows a transient increase 1 day before birth, coincident with the maximum concentration of Fru-2,6-P(2) and PFK-2 activity [10].

References