Disease relevance of Pfkl

• Fatty acid-induced beta cell hypersensitivity to glucose. Increased phosphofructokinase activity and lowered glucose-6-phosphate content [1].
• In order to determine the role of fructose (Fru) 2,6-P2 in stimulation of phosphofructokinase in ischemic liver, tissue contents of Fru-2,6-P2, hexose-Ps, adenine nucleotides, and Fru-6-P,2-kinase:Fru-2,6-bisphosphatase were investigated during the first few minutes of ischemia [2].
• Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes is associated with ATP depletion in rat cardiomyocytes [3].
• 1. The experiments with acidosis also suggest that persistent energy demands continue to stimulate phosphofructokinase despite the low pH so that glycolysis continues, with potential for injury [4].
• Hypothyroidism was associated with a drastic loss of phosphofructokinase-1 activity [5].

Psychiatry related information on Pfkl

• The marked inhibition of brain and muscles phosphofructokinase (the rate-limiting enzyme in glycolysis) induced by Li+, may play an important role in the mechanism of the therapeutic action of this agent in the manic state [6].
• The lower ATP inhibition of muscle phosphofructokinase may be partially explained by the action of potassium ions on the cooperative behavior of the enzyme [7].
• Memory facilitation and consolidation under PFK modifiers could also be demonstrated in avoidance and discrimination learning trials with honey bees and rats, which are consistent with the metabolic nature of the slow-wave rhythmicity in vertebrate microneurones thought to be the site of memory storage [8].
• Time-response curves revealed that erythrocyte hemolysis did not occur during the first 30 min of incubation with ionomycin, when the membrane skeleton-bound PFK was activated [9].

High impact information on Pfkl

• Adrenaline activation of phosphofructokinase in rat heart mediated by alpha-receptor mechanism independent of cyclic AMP [10].
• Triacsin C, an inhibitor of fatty acyl-CoA synthetase, prevented the increase in PFK activity and the lowered G6P content [1].
• These results suggest that long chain acyl-CoA mediates the rise in PFK activity, which in turn lowers the G6P level [1].
• Basal ATP content, both glucose-stimulated ATP content and ATP/ADP ratio, net lactic acid output, Vmax of phosphofructokinase-1, and Ca2+ ATPase of islets from CRF rats were lower (P less than 0.02-less than 0.01) than in normal or CRF-PTX animals [11].
• We have performed this analysis on two different K-type allosteric systems: the allosteric inhibition of rat liver phosphofructokinase by MgATP, and the allosteric activation of beef heart NAD+-dependent isocitrate dehydrogenase by ADP [12].

Chemical compound and disease context of Pfkl

• In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells [13].
• After prolonged hypothyroidism (a decrease in thyroxine of more than 10-fold), a 4-fold decrease in phosphofructokinase-1 activity was observed [5].
• It is suggested, therefore, that in addition to the increased activities of key gluconeogenic enzymes, reported earlier, a marked decrease in the activities of phosphofructokinase and pyruvate kinase and elevated level of citrate in the liver could account for the enhanced gluconeogenesis in hypervitaminosis A [14].
• It was shown that glycogen phosphorylase activity in rat heart decreased after short periods (30 min) of in vitro ischemia, whereas all other enzymes studied were not decreased up to 240 min, with the exception of lactate dehydrogenase and phosphofructokinase activities which were diminished only at 240 and 120 min of ischemia, respectively [15].
• After 8 h cold hypoxia levels of fructose-6-phosphate decreased and fructose-1,6-bisphosphate increased, thus reflecting an activation of glycolysis at the regulatory step catalysed by phosphofructokinase fructose-1,6-bisphosphatase [16].

Biological context of Pfkl

• The similarities of the rat liver-type phosphofructokinase mRNA to the human and mouse counterparts were 94% and 99% in their amino acid sequences and 88% and 94% in the nucleotide sequences of their coding regions, respectively [17].
• Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution and regulation [17].
• These results demonstrate that CAV-1 creates binding sites for PFK and ALD that may be of higher affinity than those binding sites localized in the cytoplasm [18].
• Phosphorylation contributed to the inhibition of pyruvate kinase, but several lines of evidence indicated that this reaction was not responsible for the inhibition of phosphofructokinase [19].
• Second, phosphorylation of phosphofructokinase induced by addition of cyclic AMP and Mg2+-ATP or by addition of Mg2+-ATP and the catalytic subunit of the cyclic AMP-dependent protein kinase to hepatocyte extracts had no effect on enzyme activity [19].

Anatomical context of Pfkl

• We conclude that CAV-1 functions as a scaffolding protein for PFK, ALD and perhaps other glycolytic enzymes, either through direct interaction or accessory proteins, thus contributing to compartmented metabolism in vascular smooth muscle [18].
• The localization of aldolase (ALD) was also shifted towards the plasma membrane (and colocalized with PFK) in CAV-1 over-expressing cells [18].
• Using this method to fractionate soluble tissue extracts, we identified the muscle isoform of phosphofructokinase (PFK-M) as a protein that binds to nNOS both in brain and skeletal muscle [20].
• Phosphofructokinase isozymes in pancreatic islets and clonal beta-cells (INS-1) [21].
• Rat thyroid phosphofructokinase. Comparison of the regulatory and molecular properties with those of rat muscle enzyme [22].

Associations of Pfkl with chemical compounds

• These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase [17].
• It is concluded that fructose 2,6-bisphosphate rather than fructose 1,6-bisphosphate controls, in association with other effectors, the activity of phosphofructokinase in the liver [23].
• The effect could be restored, however, by the addition of a phosphofructokinase-free extract from glucagon-treated cells to the ammonium sulfate-treated enzyme from either untreated or glucagon-treated cells [19].
• A factor that is removed from the enzyme during purification and can prevent the inhibition of phosphofructokinase by ATP has been isolated [24].
• Now, by using cells partially permeabilized to nucleotides and phosphorylated substrates, we provide evidence supporting the existence in hepatocytes of a partial control by adenosine triphosphate at phosphofructokinase, which is followed by the total control by adenosine triphosphate at pyruvate kinase [25].

Other interactions of Pfkl

• The PFK-C and PFK-A isozymes each comprised about half the total and only small amounts of the PFK-B isozyme were present in both regions [26].

Analytical, diagnostic and therapeutic context of Pfkl

• Confocal immunofluorescence microscopy was used to study the distribution of phosphofructokinase (PFK) and CAV-1 in the transfected cells [18].
• By DEAE- cellulose chromatography, PFK-L2 activity was estimated to be 2.4 units/g (41% of total phosphofructokinase activity) in fetal muscle, very low and not resolved from PFK-M in 7-day neonatal muscle, and not detectable in adult muscle [27].
• Similarly, centrifugation of [3H]oleate-treated enzyme revealed that all polymeric forms of phosphofructokinase bound approximately 6 to 8 mol of oleate/mol of enzyme [28].
• There were significant increases, over untreated diabetic rats, in phosphofructokinase activity accumulated at constrictions (p less than 0.01 for both proximal and distal) and in unconstricted nerve (p less than 0.05) [29].
• In spite of these indications of effective aldose reductase inhibition, the drug was without effect on the deficits in accumulation of activity at ligatures or unconstricted nerve levels of phosphofructokinase activity [29].

References