Activation of mammalian phosphofructokinases by ribose 1,5-bisphosphate.
Ribose 1,5-bisphosphate (Rib-1,5-P2), a newly discovered activator of rat brain phosphofructokinase, forms rapidly during the initiation of glycolytic flux and disappears within 20 s (Ogushi, S., Lawson, J.W. R., Dobson, G.P., Veech, R.L., and Uyeda, K. (1990) J. Biol. Chem. 265, 10943-10949). Activation of various mammalian phosphofructokinases and plant pyrophosphate-dependent phosphofructokinases by Rib-1,5-P2 was investigated. The order of decreasing potency for activation of rabbit muscle phosphofructokinase was: fructose (Fru) 2,6-P2, Rib-1,5-P2, Fru-1,6-P2, Glc-1,6-P2, phosphoribosylpyrophosphate, ribulose-1,5-P2, sedoheptulose-1,7-P2, and myoinositol-1,4-P2. The K0.5 values for activation by Rib-1,5-P2 of rat brain, rat liver, and rabbit muscle phosphofructokinases and potato and mung bean pyrophosphate-dependent phosphofructokinases were 64 nM, 230 nM, 82 nM, 710 nM, and 80 microM, respectively. The corresponding K0.5 values for Fru-2,6-P2 were 9, 8.6, 10, 7, and 65 nM, respectively. Rib-1,5-P2 was a competitive inhibitor of Fru-2,6-P2, binding to the muscle enzyme with Ki of 26 microM. Citrate increased the K0.5 for Rib-1,5-P2 without affecting the maximum activation, and AMP lowered the K0.5 for Rib-1,5-P2 without affecting the maximum activation. These effects of citrate and AMP were similar to those observed with Fru-2,6-P2 and different from those with Fru-1,6-P2. Rib-1,5-P2 is the second most potent activator of phosphofructokinase thus far discovered. The Rib-1,5-P2-activated conformation of the enzyme seems to be similar to that induced by Fru-2,6-P2, but different from that induced by Fru-1,6-P2.
Ishikawa
E
E
Pre-clinical Science Unit, Department of Veterans Affairs Medical Center, Dallas, Texas.
Ogushi
S
S
Ishikawa
T
T
Uyeda
K
K
D000818:Animals; D001921:Brain / Q000201:enzymology; D004789:Enzyme Activation; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D010428:Pentosephosphates / Q000138:chemical synthesis / Q000494:pharmacology*; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010944:Plants / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D013403:Sugar Phosphates / Q000494:pharmacology
D010428:Pentosephosphates; D013403:Sugar Phosphates; C050562:ribose-1,5-bisphosphate; D010732:Phosphofructokinase-1