The involvement of fructose 2,6-bisphosphate in substrate cycle control in the nonoxidative stage of the pentose phosphate pathway. A phosphorus magnetic resonance spectroscopy study

Abstract

The role of fructose 2,6-bisphosphate in the interconversion of sedoheptulose 7-phosphate and sedoheptulose 1,7-bisphosphate in rat liver cytosol fractions was studied by means of phosphorus magnetic resonance spectroscopy. When the activity of 6-phosphofructo-1-kinase was inhibited by a high concentration of ATP, the addition of fructose 2,6-bisphosphate led to a marked decrease in sedoheptulose 7-phosphate levels, accompanied by an increased concentration of ADP. Fructose 2,6-bisphosphate essentially inhibited both the decrease in sedoheptulose 1,7-bisphosphate concentration and the accumulation of Pi in the incubation mixture. The data provided evidence that fructose 2,6-bisphosphate can regulate the substrate cycle: sedoheptulose 7-phosphate<-->sedoheptulose 1,7-bisphosphate in the liver, and thus control the flux through the nonoxidative stage of the pentose phosphate pathway.

Sedoheptulose kinase regulates cellular carbohydrate metabolism by sedoheptulose 7-phosphate supply

“…These bisphosphates can be reconverted into their respective monophosphates by phosphofructose bisphophatases. A similar regulation pattern was reported for S7P and S1,7BP (see the text) [34][35][36][37][38][39][40][41]. Aldolase uses F1,6BP and S1,7BP as substrates to form DHAP and G3P or DHAP and E4P respectively.…”

“…Together, these results provide preliminary evidence for the coexistence of the hexose-and heptose-(bis)phosphate shunts ( Figure 3B). Notably, high glucose levels or incubation with F2,6BP augmented S1,7BP formation in perfused rat liver and in rat liver cytosol respectively [36,37]. Glucagon, in contrast with high glucose, favoured S1,7BP dephosphorylation and therefore S7P formation [36].…”

“…A third level of regulation is represented by generation and consumption of carbohydrate bisphosphates. Examples of carbohydrate bisphosphates found in mammals include G1,6BP (glucose 1,6-bisphosphate), F1,6BP (fructose 1,6bisphosphate), F2,6BP (fructose 2,6-bisphosphate) and the reported but rarely considered S1,7BP (sedoheptulose 1,7bisphosphate) [34][35][36][37]. The formation of S1,7BP can be partially explained by the reversible aldolase-driven condensation of E4P and DHAP [38].…”

“…The formation of S1,7BP can be partially explained by the reversible aldolase-driven condensation of E4P and DHAP [38]. It was also reported that rat and rabbit liver fractions, enriched for PFK (phosphofructokinase) activity, formed S1,7BP in the presence of S7P and ATP [37,39]. However, the kinase responsible has not been identified.…”

Cells overexpressing fructose‐2,6‐bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress

“…Inhibition of inducible PFK‐2 protein expression decreased the intracellular levels of PRPP, a product of the PPP and a precursor for nucleic acid biosynthesis. This observation suggested that the Fru‐2,6‐P 2 regulation of flux through PFK‐1 may affect the non‐oxidative PPP [11,12], which is the main source of ribose 5‐P in proliferating cells [13–15]. Moreover, the pentoses cycle contributes to the control of glucose metabolism and provides cells with NADPH for proliferation [16].…”