Activation of Mammalian Phosphofructokinases by Ribose
نویسندگان
چکیده
Ribose 1,5-bisphosphate (Rib-1,5-Pz), 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 Rib1,5-PZ was investigated. The order of decreasing potency for activation of rabbit muscle phosphofructokinase. was: fructose (Fru) 2,6-P2, Rib-1,5-Pz, Fru-1,6PZ, Glc-1,6-P*, phosphoribosylpyrophosphate, ribulose-1,5-Pz, sedoheptulose-1,7-Pz, and myoinositol1,4-PZ. The K0.6 values for activation by Rib-1,5-Pa 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 PM, respectively. The corresponding Ko.s values for Fru-2,6-Pz were 9, 8.6, 10, 7, and 65 nM, respectively. Rib-1,5-Pz was a competitive inhibitor of Fru-2,6-Pz, binding to the muscle enzyme with Ki of 26 MM. Citrate increased the KO.s for Rib-1,5-Pz without affecting the maximum activation, and AMP lowered the KO.s for Rib-1,5-Pz without affecting the maximum activation. These effects of citrate and AMP were similar to those observed with Fru-2,6-Pz and different from those with Fru1,6-PZ. Rib-1,5-Pz is the second most potent activator of phosphofructokinase thus far discovered. The Rib1,5Pz-activated conformation of the enzyme seems to be similar to that induced by Fru-2,6-P2, but different from that induced by Fru1 ,6-PZ.
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