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 se quential glycolytic enzymes that associate forming heterote tramers 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 confor mation of the enzyme. Here we show that aldolase-associated PFK dimers are not inhibited by clotrimazole, an antifulgal az ole derivative proposed as an antineoplastic drug due to its in hibitory effects on PFK. In the presence of aldolase, PFK is not modulated by its allosteric activators, ADP and fructose-2,6-bis phosphate, but is still inhibited by citrate and lactate. The asso ciation between the two enzymes also results on the twofold stimulation of aldolase maximal velocity and affinity for its sub strate. 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 metabo lism.