Muscle-Type 6-Phosphofructo-1-kinase and Aldolase Associate Conferring Catalytic Advantages for Both Enzymes

Laboratório de Oncobiologia Molecular (LabOMol), Departamento de Fármacos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
International Union of Biochemistry and Molecular Biology Life (Impact Factor: 3.14). 06/2011; 63(6):435-45. DOI: 10.1002/iub.464
Source: PubMed


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.

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Available from: Mauro Sola-Penna, May 07, 2014
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    • "Skeletal muscle aldolase has also been shown to interact and decrease the inactivation of the enzyme phosphofructokinase [15,16]. This association not only alters the allosteric regulation of phosphofructokinase but also increases the activity of aldolase by approximately 2-fold [17], which may provide an advantage for channelling substrates through the glycolytic pathway. However, skeletal muscle and liver express different aldolase isoforms, aldolase B being preferentially expressed in liver and isoform A in the skeletal muscle [18]. "
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