title: Muscle-type 6-phosphofructo-1-kinase and aldolase associate conferring catalytic advantages for both enzymes.
abstract: 6-Phosphofructo-1-kinase (PFK) and aldolase are two sequential glycolytic enzymes that associate forming heterotetramers containing a dimer of each enzyme. Although free PFK dimers present a negligible activity, once associated to aldolase these dimers are as active as the fully active tetrameric conformation of the enzyme. Here we show that aldolase-associated PFK dimers are not inhibited by clotrimazole, an antifungal azole derivative proposed as an antineoplastic drug due to its inhibitory effects on PFK. In the presence of aldolase, PFK is not modulated by its allosteric activators, ADP and fructose-2,6-bisphosphate, but is still inhibited by citrate and lactate. The association between the two enzymes also results on the twofold stimulation of aldolase maximal velocity and affinity for its substrate. These results suggest that the association between PFK and aldolase confers catalytic advantage for both enzymes and may contribute to the channeling of the glycolytic metabolism.
authors.affiliation: Laboratório de Oncobiologia Molecular (LabOMol), Departamento de Fármacos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariah Celestino
authors.initials: MC
authors.lastname: Marcondes
authors.forename: Mauro
authors.initials: M
authors.lastname: Sola-Penna
authors.forename: Renan da Silva Gianoti
authors.initials: Rda S
authors.lastname: Torres
authors.forename: Patricia
authors.initials: P
authors.lastname: Zancan
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D002384:Catalysis; D003022:Clotrimazole / Q000378:metabolism; D019281:Dimerization; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006019:Glycolysis; D018482:Muscle, Skeletal / Q000201:enzymology; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011817:Rabbits; D013050:Spectrometry, Fluorescence
chemical_list: D000935:Antifungal Agents; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase; D003022:Clotrimazole