Disease relevance of FBP1

• FBPase proteins with G164S or A177D mutations were enzymatically inactive when purified from E. coli [1].
• Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis [2].
• Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus [3].
• HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase [4].
• Graft ischemia correlates with urinary excretion of the proximal marker enzyme fructose-1,6-bisphosphatase in human kidney transplantation [5].

Psychiatry related information on FBP1

• The capacity for glycolysis in muscle biopsies obtained from long-term heavy alcohol drinking patients has been compared with tissue from control subjects by assay in vitro of the total activities of glycogen phosphorylase, phosphofructokinase and fructose 1,6-bisphosphatase, key regulatory enzymes in the anaerobic glycolytic pathway [6].

High impact information on FBP1

• The protein products of these genes, designated floral binding protein 1 (FBP1) and 2 (FBP2), are putative transcription factors with the MADS box DNA binding domain [7].
• Our results suggest a regulation of the fbp1 gene expression by the green petals (gp) gene [7].
• MB06322 (CS-917): A potent and selective inhibitor of fructose 1,6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes [8].
• In an effort to find safe and efficacious GNG inhibitors, we targeted the AMP binding site of fructose 1,6-bisphosphatase (FBPase) [8].
• Thus, we have found the FBPase that was 'missing' in thermophiles and shown that it also functions as an IMPase [9].

Chemical compound and disease context of FBP1

• Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in zucker diabetic Fatty rats [10].
• Fructose-1,6-bisphosphate (FBP) is a high-energy glycolytic intermediate that decreases the effects of ischemia; it has been used successfully in organ perfusion and preservation [11].
• This data extends the neuroprotective profile of FBP in neonatal brain injury and identifies gray matter lesions involving N-methyl-D-aspartate receptors as a major target for this promising drug [12].
• The tetramer-dimer ratio is regulated by ATP, FBP and serine and by direct interactions with different oncoproteins (pp60v-src, HPV-16 E7) [13].
• The campylobacter supplement ferrous sulphate, sodium metabisulphite, sodium pyruvate (FBP) (Oxoid) was inhibitory for some isolates; the inhibitory component was found to be sodium metabisulphite [14].

Biological context of FBP1

• FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span > 31 kb, and the six introns are in the same position as in the rat gene [2].
• PhBX appears to be a gene that specifically interacts with the FBP1 gene, and is involved in the up-regulation of FBP1 [15].
• FBPase deficiency is an autosomal recessive inherited disorder caused by distraction of the fructose-1,6-bisphosphatase 1 gene (FBP1) and features severely impaired gluconeogenesis [16].
• Glycolysis is regulated by ras via the activity of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFK2/FBPase), which modulate the intracellular concentration of the allosteric glycolytic activator, fructose-2,6-bisphosphate (F2,6BP) [17].
• Interestingly, FBPase was also present in pancreas and cortex cells of the adrenal gland, organs that are involved in the control of carbohydrate and lipid metabolism [18].

Anatomical context of FBP1

• FBP1, together with other members of the family, were all induced in cell cultures by elicitor action although they all showed some expression in non-induced cultured cells [19].
• We reported the first case of molecular diagnosis of FBPase deficiency, using cultured monocytes as a source for FBPase mRNA [1].
• Our data also show that this FBPase-encoding mRNA can be activated during monocytic maturation since it was detected in human alveolar macrophages [20].
• These results suggest that FBPase may participate as a component of a metabolic sensing mechanism present in the pancreas [21].
• Immunolocalization analysis showed that FBPase is expressed both in human and rat Langerhans islets, specifically in beta cells [21].

Associations of FBP1 with chemical compounds

• In the classic view, F26P(2) regulates glucose metabolism by allosteric effects on 6-phosphofructo-1-kinase (6PFK1, activation) and fructose-1,6-bisphosphatase (FBPase, inhibition) [22].
• However, FBP1 when expressed in Pichia pastoris generated H2O2 using cysteine at pH 7.2, a specific property of the native protein when isolated from suspension-cultured cells [19].
• Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 2,6-bisphosphate, AMP, and Zn2+ at 2.0-A resolution: aspects of synergism between inhibitors [23].
• This gene encodes two closely related mRNAs; one, activated by 1,25-(OH)2D3 at an early stage of HL-60 differentiation, encodes a protein that has homology to mammalian FBPase, a key enzyme in gluconeogenesis, although it does not exhibit its classical enzymatic activity [20].
• Approximately 50% of the expressed human fructose-1,6-bisphosphatase was soluble and enzymatically active, and the enzyme was purified to homogeneity by heat treatment, ammonium sulfate fractionation, and substrate/AMP elution from carboxymethyl-Sephadex [24].

Enzymatic interactions of FBP1

• Two kinetically and thermodynamically distinct thiol/disulfide redox changes are observed during the reversible thioredoxin fb-catalyzed reduction and oxidation of spinach chloroplast fructose-1,6-bisphosphatase by dithiothreitol [25].

Regulatory relationships of FBP1

• Like their chloroplast counterparts, N. muscorum FBPase and SBPase were activated preferentially by reduced thioredoxin f [26].
• Fructose-induced changes in FBPase activity may regulate changes in GLUT5 expression and activity in the small intestine of neonatal rats [27].
• The omission of catalase inhibited net photosynthesis and caused a lower sulfhydryl number along with diminished fructose-1,6-bisphosphatase activity [28].

Other interactions of FBP1

• Therefore, we analyzed the human tissue localization and cellular distribution of FBPase and PEPCK immunohistochemically [18].
• Mutant sequences were identified that were incapable of destabilizing a reporter mRNA, yet showed unimpaired binding of FBP1 and AUF-1 and/or -2 [29].
• 6-Phosphofructo-2-kinase catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, activator of phosphofructokinase-1 and inhibitor of fructose 1,6-bisphosphatase [30].
• The activities of glucose-6-phosphatase, fructose-1,6-bisphosphatase, acid phosphatase and glucose-6-phosphate dehydrogenase varied less, although in each case the activity was significantly lower in the mammalian stage [31].
• The ability of thioredoxin f to form an electrostatic (non-covalent) complex, earlier found with fructose-1,6-bisphosphatase, was extended to include 27 previously unrecognized proteins functional in 11 processes of chloroplasts [32].

Analytical, diagnostic and therapeutic context of FBP1

• PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene were designed and used to isolate a cosmid clone [3].
• Sequence analysis of the cDNA of the fructose-1,6-bisphosphatase mRNA isolated from monocytes from a girl with this disease and her consanguineous parents revealed that the patient and her parents were a homozygote and heterozygotes for an insertion of one G residue at G957GGGG961, respectively [33].
• Multiple regression revealed a significant correlation between cold ischemia time and posttransplant urinary FBPase excretion (multiple R = 0.65, p < 0.001) [5].
• Additional evidence was obtained for interaction of MDH2 with PCK1 using Hummel-Dreyer gel filtration chromatography, and for interactions of MDH2 with PCK1 and with FBP1 using surface plasmon resonance [34].
• On Northern blot analysis, this rearrangement was reflected in the enhanced expression (greater than 100-fold) of a FBP1-specific transcript which was 200 nucleotides shorter than the corresponding L1210 parental transcript [35].

References