On the mechanism of fructose 1,6-diphosphatase: Inhibition by methyl d-fructoside 1,6-diphosphate

Mechanism of action of fructose 1,6-diphosphatase. Inhibition by structural analogs of fructose 1,6-diphosphate

“…In an earlier paper (Benkovic et al, 1970) phosphate appeared hyperbolic rather than linear. However, the plot may indeed be linear as values at higher inhibitor concentrations are lowered by increased ionic strength which effects a decrease in enyzme activity.…”

“…Replacement of the 2-OH by OCH3 (II and IV) or (III and V) converts the sugar diphosphate from a substrate into an inhibitor. Other diphosphates, glucose 1,6, cA-2,5-bis-(hydroxymethyl)tetrahydrofuran, the unresolved mixture of D-mannitol and o-sorbitol 1,6- (Benkovic et al, 1970), and 1,6-hexanediol, act neither as substrates nor inhibitors. It now appears that the most reactive substrate for FDPase should contain two phosphoryl moieties (1-6) and a furanose configuration bearing hydroxyl groups at C-3 and C-4.…”

Fructose 2,6‐Bisphosphate

“…In contrast with the truly competitive inhibitor methylfructose 1,6-bisphosphate (Benkovic et al, 1970), Fru-2,6-P2 changes the shape of the saturation curve and acts synergistically with AMP (previously mentioned).…”

“…The conversion of Fru-l,6-P2 into Fru-6-P and Pi is catalyzed by a specific fructose 1,6-bisphosphatase (reviewed by Benkovic and de Maine, 1982;Tejwani, 1983). The abundance of this enzyme varies from organ to organ, being highest in the liver and in the kidney (8-10 U/g at 25"C), which are responsible for gluconeogenesis in animals.…”

“…Only 1 mol of Fru-2,6-P2 can bind per enzyme subunit and this binding is antagonized by methylfructose 1,6-bisphosphate (Mc Grane et al, 1983), a truly competitive inhibitor of FBPase 1 (Benkovic et al, 1970). However, the binding of Fru-2,6-P2 requires the presence of Mg2+ (Mc Grane et al, 1983; Van Schaftingen, unpublished results; see, however, , whereas that of Fru-1,6-P2 does not.…”