Disease relevance of Pfkl

• Increased phosphofructokinase activity, a result of gene dosage, is commonly found in erythrocytes and fibroblasts from Down's syndrome patients [1].
• Characteristic regulatory properties of ascites tumor PFK, i.e. insensitivity to fructose-1,6-P2 activation and inhibition by P-enolpyruvate, were also observed in the mammary gland isozyme [2].
• The effect of Mg2+ upon 6-phosphofructokinase activity in Ehrlich ascites tumor cells in vivo [3].
• Phosphofructokinase and pyruvate kinase in mouse embryonal carcinoma P19 cells in relation to growth and differentiation [4].
• Altered allosteric properties of cytoskeleton-bound phosphofructokinase in muscle from mice with X chromosome-linked muscular dystrophy (mdx) [5].

Psychiatry related information on Pfkl

• Time-response studies with Ca(2+)-ionophore A23187 have revealed dual effects on the distribution of phosphofructokinase (PFK) (EC 2.7.1.11), the rate-limiting enzyme of glycolysis, between the cytoskeletal and cytosolic (soluble) fractions of the cell [6].

High impact information on Pfkl

• Muscle phosphofructokinase deficiency. Biochemical and immunological studies of phosphofructokinase isozymes in muscle culture [7].
• Muscle cultures from three unrelated patients with muscle phosphofructokinase (PFK; EC 2.7.1.11) deficiency (Glycogenosis type VII; Tarui disease) had normal PFK activity and normal morphology [7].
• MDA-MB-231 cells isolated from tumors exhibited profound differences in their enzyme activity profiles compared with the parent cell line, including the dramatic posttranscriptional up-regulation of the serine proteases urokinase plasminogen activator and tissue plasminogen activator and down-regulation of the glycolytic enzyme phosphofructokinase [8].
• The decrease in 3H2O formation from [5-3H]glucose and the metabolite pattern that results from the addition of low concentrations (less than or equal to 0.25 mM) of 2,5-anhydromannitol indicate an inhibition at phosphofructokinase-1 that cannot be attributed to a decrease in the cellular content of fructose-2,6-P2 [9].
• Unlike mAkt-expressing cells, however, they did not consume more glucose, did not maintain prolonged phosphofructokinase-1 protein levels and activity, and did not maintain pentose phosphate shuttle activity in the absence of growth factor [10].

Chemical compound and disease context of Pfkl

• In this study, we investigated (a) the roles of fructose 2,6-bisphosphate (Fru-2,6-P2) and ribose 1,5-bisphosphate (Rib-1,5-P2), potent activators of phosphofructokinase, (b) the enzymes responsible for the synthesis of Rib-1,5-P2, and (c) the mechanisms of regulation of these enzymes in H36.12j macrophages during the initial phase of hypoxia [11].
• Pretreatment with 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine and calphostin C prevented the activation of ribose PRPP synthetase and PRPP pyrophosphatase as well as increase in Rib-1,5-P2 and activation of phosphofructokinase 30 s after hypoxia [11].
• The specific activities of pyruvate kinase and phosphofructokinase but not lactate dehydrogenase increase as P-815 mastocytoma cells approach the stationary phase [12].
• Taxol (paclitaxel) induces a detachment of phosphofructokinase from cytoskeleton of melanoma cells and decreases the levels of glucose 1,6-bisphosphate, fructose 1,6-bisphosphate and ATP [13].
• We report here that the local anesthetics, lidocaine and bupivacaine, induced a dose-dependent detachment of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13), from cytoskeleton of B16 melanoma cells [14].

Biological context of Pfkl

• The specific chromosome complements of the hybrid cell lines and the presence or absence of hybridizing mouse sequences in their DNAs allow us to assign all five sequences to mouse Chromosome 10, with the assignment of Pfkl reported here for the first time [15].
• We have mapped mouse Aire to mouse chromosome 10 by FISH, to the same region as Pwp2 and Pfkl, confirming synteny to the corresponding region of human chromosome 21 [16].
• Isozyme expression of phosphofructokinase (PFK), the key regulatory enzyme for glycolysis, was studied during differentiation of mouse C2 myoblasts to myotubes [17].
• The total PFK activity increased 20-fold during in vitro myogenesis [17].
• These results indicate isozyme-specific control of muscle PFK gene expression during C2 myoblast differentiation [17].

Anatomical context of Pfkl

• Phosphofructokinase isozyme expression during myoblast differentiation [17].
• Mouse liver mRNA enriched in sequences coding for liver phosphofructokinase by polysome immunoadsorption was used as a template for the synthesis of cDNA [18].
• Analysis of phosphofructokinase subunits and isozymes in ascites tumor cells and its original tissue, murine mammary gland [2].
• Fibroblast growth factor-1 induces phosphofructokinase, fatty acid synthase and Ca(2+)-ATPase mRNA expression in NIH 3T3 cells [19].
• The findings that cytoskeletal PFK in mdx muscle, although altered, remains bound to cytoskeleton may play a role in muscle structure and function and the mild clinical symptoms in mdx mice [5].

Associations of Pfkl with chemical compounds

• Conceivably, a selective overexpression of the PFKL isoform in Tg-PFKL mice altered the enzymatic properties of the tetrameric PFK and thereby affected glucose metabolism [20].
• The N-half of the liver phosphofructokinase has conserved substrate binding sites for ATP and fructose-6-P [18].
• The induction of liver phosphofructokinase mRNA by fasting/refeeding was also diminished in streptozotocin diabetic mice [18].
• The strong enhancement of FDP/G6P ratio is taken as evidence for in vivo stimulation of phosphofructokinase 1 (PFK) (ATP:D-fructose-6-phosphate 1-phosphotransferase; EC 2.7.1.11) [3].
• It is concluded that the two inhibitors, ATP and citrate, of mammalian PFK interact with sites that have evolved from the duplicated phosphoenolpyruvate/ADP allosteric site of the ancestral PFK [21].

Regulatory relationships of Pfkl

• PFK-A mRNA was more abundantly expressed in all tissues than were the PFK-B and PFK-C genes [22].

Other interactions of Pfkl

• The mouse PFK-C gene organization is similar to that of the human and rabbit PFK-A and human and mouse PFK-B genes [22].
• Compared with the muscle (A-type) phosphofructokinase gene, the sizes of the introns are different although exon lengths are highly conserved [23].
• The glycolytic enzymes phosphofructokinase, pyruvate kinase, aldolase and lactic acid dehydrogenase showed increased activities in leukaemic conditions [24].
• Chronic treatment of C57Bl/6 ob/ob mice with the thermogenic beta-adrenoceptor agonist BRL 26830 increased the maximal activities of hexokinase and phosphofructokinase 2- and 3-fold respectively in interscapular brown adipose tissue [25].
• Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio [26].

Analytical, diagnostic and therapeutic context of Pfkl

• Subsequently, by selecting antibodies specific to fusion proteins expressed by putative clones and by reacting with Western blots of mouse liver proteins several clones were positively identified as containing liver phosphofructokinase sequences [18].
• The liver phosphofructokinase mRNA level increased 4-fold when previously starved mice were refed a high carbohydrate, fat-free diet [18].
• Here, site-directed mutagenesis of two arginine residues (Arg-433 and Arg-429) of mouse phosphofructokinase is used to identify the ATP inhibitory site, and, by inference, the AMP/ADP site [21].
• Sera from mice that were acutely or chronically infected or multiply exposed to irradiated cercariae did not recognize recombinant schistosome PFK in either Western blotting or ELISA [27].
• A polyclonal antibody against purified PFK from Fasciola hepatica was affinity purified using recombinant PFK and used in combination with immunogold labelling to identify PFK by transmission electron microscopy in cryosections [27].

References