The PFKL mRNA sequence includes 55nucleotides at the5' and 515 nucleotides at the3'noncoding regions, as well as 2,337 nucleotides in the coding region, encoding 779amino acids. This coding region only shares a 68% similarity between PFKL and the muscle-typePFKM.[6]
This 80-kDa protein is one of three subunit types that comprise the five tetrameric PFKisozymes. The liver PFK (PFK-5) contains solely PFKL, while theerythrocyte PFK includes five isozymes composed of different combinations of PFKL and the second subunit type, PFKM.[7][8] The muscle isozyme (PFK-1) is composed solely of PFKM.[7][9][10] These subunits evolved from a commonprokaryotic ancestor viagene duplication and mutation events. Generally, theN-terminal of the subunits carries out their catalytic activity while theC-terminal containsallostericligand binding sites[11]
This gene encodes one of three protein subunits of PFK, which are expressed and combined to form the tetrameric PFK in a tissue-specific manner. As a PFK subunit, PFKL is involved in catalyzing thephosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. This irreversible reaction serves as the majorrate-limiting step of glycolysis.[7][10][11][12] Notably,knockdown ofPFKL has been shown to impair glycolysis and promote metabolism via thepentose phosphate pathway. Moreover, PFKL regulatesNADPH oxidase activity through the pentose phosphate pathway and according toNADPH levels.[12]
As the erythrocyte PFK is composed of both PFKL and PFKM, thisheterogeneic composition is attributed with the differential PFK activity and organ involvement observed in some inherited PFK deficiency states in whichmyopathy orhemolysis or both can occur, such asglycogenosis type VII (Tarui disease).[7][8]
Overexpression of PFKL has been associated withDown's syndrome (DS) erythrocytes andfibroblasts and attributed withbiochemical changes in PFK that enhance its glycolytic function. Moreover, thePFKL gene maps to the triplicated region of chromosome 21 responsible for DS, indicating that this gene, too, has been triplicated.[13]
^Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y (December 1989). "The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK".DNA.8 (10):733–43.doi:10.1089/dna.1989.8.733.PMID2533063.
^abKoster JF, Slee RG, Van Berkel TJ (April 1980). "Isoenzymes of human phosphofructokinase".Clinica Chimica Acta; International Journal of Clinical Chemistry.103 (2):169–73.doi:10.1016/0009-8981(80)90210-7.PMID6445244.
^abMusumeci O, Bruno C, Mongini T, Rodolico C, Aguennouz M, Barca E, Amati A, Cassandrini D, Serlenga L, Vita G, Toscano A (April 2012). "Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII)".Neuromuscular Disorders.22 (4):325–30.doi:10.1016/j.nmd.2011.10.022.PMID22133655.S2CID20133199.
^Elson A, Bernstein Y, Degani H, Levanon D, Ben-Hur H, Groner Y (March 1992). "Gene dosage and Down's syndrome: metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase".Somatic Cell and Molecular Genetics.18 (2):143–61.doi:10.1007/bf01233161.PMID1533471.S2CID38259672.
Kahn A, Meienhofer MC, Cottreau D, Lagrange JL, Dreyfus JC (April 1979). "Phosphofructokinase (PFK) isozymes in man. I. Studies of adult human tissues".Human Genetics.48 (1):93–108.doi:10.1007/bf00273280.PMID156693.S2CID23300861.
Kristensen T, Lopez R, Prydz H (1992). "An estimate of the sequencing error frequency in the DNA sequence databases".DNA Sequence.2 (6):343–6.doi:10.3109/10425179209020815.PMID1446073.
Elson A, Levanon D, Brandeis M, Dafni N, Bernstein Y, Danciger E, Groner Y (May 1990). "The structure of the human liver-type phosphofructokinase gene".Genomics.7 (1):47–56.doi:10.1016/0888-7543(90)90517-X.PMID2139864.
Levanon D, Danciger E, Dafni N, Bernstein Y, Elson A, Moens W, Brandeis M, Groner Y (December 1989). "The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK".DNA.8 (10):733–43.doi:10.1089/dna.1989.8.733.PMID2533063.
Van Keuren M, Drabkin H, Hart I, Harker D, Patterson D, Vora S (September 1986). "Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody".Human Genetics.74 (1):34–40.doi:10.1007/bf00278782.PMID2944814.S2CID26346007.
Koster JF, Slee RG, Van Berkel TJ (April 1980). "Isoenzymes of human phosphofructokinase".Clinica Chimica Acta; International Journal of Clinical Chemistry.103 (2):169–73.doi:10.1016/0009-8981(80)90210-7.PMID6445244.
Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides".Nature Biotechnology.21 (5):566–9.doi:10.1038/nbt810.PMID12665801.S2CID23783563.
Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells".Nature Biotechnology.23 (1):94–101.doi:10.1038/nbt1046.PMID15592455.S2CID7200157.
