Regulation of mammalian muscle type 6-phosphofructo-1-kinase and its implication for the control of the metabolism.
Phosphofructokinase (PFK) is a major regulatory glycolytic enzyme and is considered to be the pacemaker of glycolysis. This enzyme presents a puzzling regulatory mechanism that is modulated by a large variety of metabolites, drugs, and intracellular proteins. To date, the mammalian enzyme structure has not yet been resolved. However, it is known that PFK undergoes an intricate oligomerization process, shifting among monomers, dimers, tetramers, and more complex oligomeric structures. The equilibrium between PFK dimers and tetramers is directly correlated with the enzyme regulation, because the dimer exhibits very low catalytic activity, whereas the tetramer is fully active. Several PFK ligands modulate the enzyme, favoring the formation of its dimers or tetramers. The present review integrates recent findings regarding the regulatory aspects of muscle type PFK and discusses their relation to the control of metabolism.
Laboratorio de Enzimologia e Controle do Metabolismo (LabECoM) and Laboratório de Oncobiologia Molecular (LabOMol), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. maurosp@ufrj.br
Mauro
M
Sola-Penna
Daniel
D
Da Silva
Wagner S
WS
Coelho
Monica M
MM
Marinho-Carvalho
Patricia
P
Zancan
D000199:Actins / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D025203:Phosphofructokinase-1, Muscle Type / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
D000199:Actins; D001457:Anion Exchange Protein 1, Erythrocyte; D002147:Calmodulin; D005635:Fructosediphosphates; C027652:fructose 2,6-diphosphate; D025203:Phosphofructokinase-1, Muscle Type; D002118:Calcium