[Fructose 1,6-diphosphate can be a substrate to accelerate glycolysis].
Fructose 1,6-diphosphate (F1, 6P) is a glycolytic intermediate which has already been used clinically to treat congestive heart failure. F1, 6P has been shown experimentally to improve glycolytic flux, although theoretical background is unclear. Since there is two possible mechanism of F1, 6P effect on acceleration of glycolysis, including pharmacological effect and substrate effect, we sought to determine the real mechanism of action of F1, 6P on glycolysis. Langendorff-perfused rabbit hearts were infused with F1, 6P (5 and 10 mM) in a first group, and in a second group, 30 minutes of perfusion with modified Krebs-Henselit (K-H) buffer with reduced glucose concentration (5 mM), plus 2-deoxy glucose (5 mM) and with or without 10 mM F1, 6P followed by 30 minutes of wash with normal K-H buffer. We measured contractile function, oxygen consumption, and high energy phosphate by 31p-NMR spectroscopy. In the first group of experiments, F1, 6P resulted in a dose dependent increase in high energy phosphate production and inorganic phosphate (Pi). There was also a marked decline in developed pressure (Dev P) due mostly to the ability of F1, 6P to chelate calcium. Intracellular Mg2+ which was also reduced during F1, 6P infusion might be related to intracellular Ca2+ and/or accelerated glycolysis. In the model of glycolysis inhibited by 2-DG, Dev P was consistently decreased during the infusion of 2-DG, and wash-out period along with the deterioration of high energy phosphate. However, F1, 6P could provide excellent recovery of contractile function after wash along with superior high energy potential during the 2-DG infusion and wash.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeuchi
K
K
Division of Cardiothoracic Surgery, University of Pittsburgh, School of Medicine.
Takashima
K
K
Suzuki
S
S
Fukui
K
K
del Nido
P J
PJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003847:Deoxyglucose / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D005635:Fructosediphosphates / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011817:Rabbits
D005635:Fructosediphosphates; D003847:Deoxyglucose; D008274:Magnesium; C029063:fructose-1,6-diphosphate; D002118:Calcium