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Bailliere's Best Practice & Research.... Mar 2000Phosphoglycerate kinase (PGK) deficiency is associated with hereditary haemolytic anaemia and often with central nervous system dysfunction and/or myopathy. Twenty-three... (Review)
Review
Phosphoglycerate kinase (PGK) deficiency is associated with hereditary haemolytic anaemia and often with central nervous system dysfunction and/or myopathy. Twenty-three families have been discovered with this condition. Nine have manifested both symptoms, six only haemolysis, and seven central nervous system dysfunction and/or myopathy without haemolysis; one case is asymptomatic. Among them, the structural abnormalities of 14 mutants, including 11 missense mutations, 1 gene deletion, 1 gene insertion, and 1 splicing mutation, have been identified. The correlation between the phenotypic and structural differences in PGK deficiency remains to be defined. Splenectomy obviates transfusion in most patients but does not correct the haemolytic disorder. Phosphofructokinase (PFK) deficiency is associated with myopathy and/or haemolysis. More than half reported had the typical features of glycogen storage disease type VII (Tarui disease). The other cases exhibited myopathy alone, haemolytic anaemia alone, or no clinical symptom at all. Eight missense, 1 nonsense, 1 frameshift and 5 splicing mutations have been determined in the PFK-M gene. In classic PFK-M deficiency, the avoidance of undue exertion is the key to prevent muscle symptoms.
Topics: Anemia, Hemolytic, Congenital; Animals; Erythrocytes; Humans; Models, Molecular; Molecular Structure; Mutation; Phosphofructokinase-1; Phosphoglycerate Kinase
PubMed: 10916683
DOI: 10.1053/beha.1999.0062 -
Analytical Biochemistry Feb 2014An assay was developed for phosphofructokinase-1 (PFK-1) using capillary electrophoresis (CE). In the glycolytic pathway, this enzyme catalyzes the rate-limiting step...
An assay was developed for phosphofructokinase-1 (PFK-1) using capillary electrophoresis (CE). In the glycolytic pathway, this enzyme catalyzes the rate-limiting step from fructose-6-phosphate and magnesium-bound adenosine triphosphate (Mg-ATP) to fructose-1,6-bisphosphate and magnesium-bound adenosine diphosphate (Mg-ADP). This enzyme has recently become a research target because of the importance of glycolysis in cancer and obesity. The CE assay for PFK-1 is based on the separation and detection by ultraviolet (UV) absorbance at 260 nm of Mg-ATP and Mg-ADP. The separation was enhanced by the addition of Mg²⁺ to the separation buffer. Inhibition studies of PFK-1 by aurintricarboxylic acid and palmitoyl coenzyme A were also performed. An IC₅₀ value was determined for aurintricarboxylic acid, and this value matched values in the literature obtained using coupled spectrophotometric assays. This assay for PFK-1 directly monitors the enzyme-catalyzed reaction, and the CE separation reduces the potential of spectral interference by inhibitors.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Electrophoresis, Capillary; Enzyme Assays; Enzyme Inhibitors; Phosphofructokinase-1; Rabbits
PubMed: 24444856
DOI: 10.1016/j.ab.2013.10.028 -
Experientia. Supplementum 1976
Comparative Study
Topics: Adenosine Triphosphate; Amino Acid Sequence; Amino Acids; Geobacillus stearothermophilus; Gram-Negative Aerobic Bacteria; Hot Temperature; Kinetics; Molecular Weight; Phosphofructokinase-1
PubMed: 133030
DOI: 10.1007/978-3-0348-7675-9_16 -
Methods in Enzymology 1975
Topics: Acetates; Acetone; Allosteric Regulation; Ammonium Sulfate; Autolysis; Chromatography; Dansyl Compounds; Electrophoresis, Polyacrylamide Gel; Escherichia coli; Fractional Precipitation; Hot Temperature; Hydrogen-Ion Concentration; Magnesium; Methods; Molecular Weight; Phosphofructokinase-1; Spectrophotometry
PubMed: 237208
DOI: 10.1016/0076-6879(75)42099-7 -
Methods in Enzymology 1975
Topics: Ammonium Sulfate; Animals; Chromatography, Affinity; Chromatography, Gel; Fractional Precipitation; Hot Temperature; Liver; Methods; Muscles; Phosphofructokinase-1; Rabbits
PubMed: 124386
DOI: 10.1016/0076-6879(75)42095-x -
Methods in Enzymology 1982
Topics: Bacillus; Drug Stability; Enzyme Activation; Kinetics; Macromolecular Substances; Molecular Weight; Phosphofructokinase-1
PubMed: 6218376
DOI: 10.1016/s0076-6879(82)90108-2 -
Methods in Enzymology 1982
Topics: Adenosine Diphosphate; Ammonia; Cations; Enzyme Activation; Hydrogen-Ion Concentration; Kinetics; Lactococcus lactis; NAD; Phosphofructokinase-1; Spectrophotometry, Ultraviolet
PubMed: 6218377
DOI: 10.1016/s0076-6879(82)90109-4 -
Methods in Enzymology 1975
Topics: Chemical Phenomena; Chemistry; Chromatography, Affinity; Chromatography, DEAE-Cellulose; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Hemolysis; Humans; Kinetics; Methods; Molecular Weight; Muscles; Phosphofructokinase-1; Spectrophotometry
PubMed: 124385
DOI: 10.1016/0076-6879(75)42101-2 -
Journal of Molecular and Cellular... Jan 2022Glucose metabolism comprises numerous amphibolic metabolites that provide precursors for not only the synthesis of cellular building blocks but also for ATP production....
Glucose metabolism comprises numerous amphibolic metabolites that provide precursors for not only the synthesis of cellular building blocks but also for ATP production. In this study, we tested how phosphofructokinase-1 (PFK1) activity controls the fate of glucose-derived carbon in murine hearts in vivo. PFK1 activity was regulated by cardiac-specific overexpression of kinase- or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgenes in mice (termed Glyco or Glyco mice, respectively). Dietary delivery of C-glucose to these mice, followed by deep network metabolic tracing, revealed that low rates of PFK1 activity promote selective routing of glucose-derived carbon to the purine synthesis pathway to form 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Consistent with a mechanism of physical channeling, we found multimeric protein complexes that contained phosphoribosylaminoimidazole carboxylase (PAICS)-an enzyme important for AICAR biosynthesis, as well as chaperone proteins such as Hsp90 and other metabolic enzymes. We also observed that PFK1 influenced glucose-derived carbon deposition in glycogen, but did not affect hexosamine biosynthetic pathway activity. These studies demonstrate the utility of deep network tracing to identify metabolic channeling and changes in biosynthetic pathway activity in the heart in vivo and present new potential mechanisms by which metabolic branchpoint reactions modulate biosynthetic pathways.
Topics: Animals; Biosynthetic Pathways; Glucose; Glycolysis; Mice; Myocardium; Phosphofructokinase-1; Phosphofructokinase-2; Phosphofructokinases
PubMed: 34487754
DOI: 10.1016/j.yjmcc.2021.08.013 -
Archives of Biochemistry and Biophysics Jul 2023The phosphofructokinase (Pfk) reaction represents one of the key regulatory points in glycolysis. While most organisms encode for Pfks that use ATP as phosphoryl donor,...
The phosphofructokinase (Pfk) reaction represents one of the key regulatory points in glycolysis. While most organisms encode for Pfks that use ATP as phosphoryl donor, some organisms also encode for PP-dependent Pfks. Despite this central role, the biochemical characteristics as well as the physiological role of both Pfks is often not known. Clostridium thermocellum is an example of a microorganism that encodes for both Pfks, however, only PP-Pfk activity has been detected in cell-free extracts and little is known about the regulation and function of both enzymes. In this study, the ATP- and PP-Pfk of C. thermocellum were purified and biochemically characterized. No allosteric regulators were found for PP-Pfk amongst common effectors. With fructose-6-P, PP, fructose-1,6-bisP, and P PP-Pfk showed high specificity (K < 0.62 mM) and maximum activity (V > 156 U mg). In contrast, ATP-Pfk showed much lower affinity (K of 9.26 mM) and maximum activity (14.5 U mg) with fructose-6-P. In addition to ATP, also GTP, UTP and ITP could be used as phosphoryl donors. The catalytic efficiency with GTP was 7-fold higher than with ATP, suggesting that GTP is the preferred substrate. The enzyme was activated by NH, and pronounced inhibition was observed with GDP, FBP, PEP, and especially with PP (K of 0.007 mM). Characterization of purified ATP-Pfks originating from eleven different bacteria, encoding for only ATP-Pfk or for both ATP- and PP-Pfk, identified that PP inhibition of ATP-Pfks could be a common phenomenon for organisms with a PP-dependent glycolysis.
Topics: Phosphofructokinases; Clostridium thermocellum; Diphosphates; Amino Acid Sequence; Phosphofructokinase-1; Bacteria; Adenosine Triphosphate; Guanosine Triphosphate; Kinetics
PubMed: 37380119
DOI: 10.1016/j.abb.2023.109676