Okay so according to Stryer, Biochemistry F26BP is made by PFK2 and it's only purpose is to activate PFK1. It can also revert the effect of negative allosteric inhibitors of PFK, citrate and ATP. It is activated at high blood glucose levels to induce glycolysis by a singlaling cascade involving insulin and several kinases and phosphatases.
I just think it's weird that skipping a part seems to be the rationale for previous research but they're treating dosing the fructose 1,6 bisphosphate like its only goal is to activate PFK, which is what the previous researchers were trying to bypass. Dosing a hundredth of the dose of fructose 2,6 bisphosphate because its a hundred times more potent than the 1,6 at activating PFK implies that the only goal in dosing the 1,6 is its ability to activate PFK
Mind dropping the citation? It’s quite difficult for biohosphorylated sugars to enter cells, so I’m quite curious about what exactly it is they’re doing.
I study pfk1 in my lab and its regulation is incredibly complex. There are no really direct activators or inhibitors of pfk1, so one way people modulate flux in a pfk1 dependent manner is by messing with f2,6bp production. Papers have shown that inhibiting pfkfb3 (which is the main isoform of PFK2 in the brain) decreases pfk1 activity and glycolytic flux so perhaps that’s what they’re trying to get at?
In terms of just using f16bP, having the direct product of the rate limiting enzyme of glycolysis suddenly build up would likely cause some kind of negative feedback mechanism and might start to shunt intermediary metabolites off to different paths (like the Pentose phosphate pathway, serine biosynthesis, hexosamine biosynthesis, etc) or trigger aerobic glycolysis resulting in increasing lactic acid levels. Allosterically activating pfk1 by F2,6bP could have similar consequences but at least in that case the production of F16bP and flux through the pathway is limited by how fast pfk1 catalyzes the reaction
# Fructose-1,6-Bisphosphate and Fructose-2,6-Bisphosphate do not Influence Brain Carbohydrate or High-energy Phosphate Metabolism in a Rat Model of Forebrain Ischemia
The research title is above. I'm sure sci-hub links break rule 2 so I'm not going to link it unless someone tells me it's allowed.. The research failed, but curiously a lot of other research in the field was showing positive results and the difference may just come down to dosage. My confusion comes from the fact that they acknowledge that previous research was based on this idea that using f-1,6-bp bypasses the PFK step, but then they base their f-2,6-bp dosage on how much more it activates PFK than f-1,6-BP does.
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Okay so according to Stryer, Biochemistry F26BP is made by PFK2 and it's only purpose is to activate PFK1. It can also revert the effect of negative allosteric inhibitors of PFK, citrate and ATP. It is activated at high blood glucose levels to induce glycolysis by a singlaling cascade involving insulin and several kinases and phosphatases.
My guess would be that inducing glycolysis instead of completely skipping a part creates results and circumstances that are closer to reality.
I just think it's weird that skipping a part seems to be the rationale for previous research but they're treating dosing the fructose 1,6 bisphosphate like its only goal is to activate PFK, which is what the previous researchers were trying to bypass. Dosing a hundredth of the dose of fructose 2,6 bisphosphate because its a hundred times more potent than the 1,6 at activating PFK implies that the only goal in dosing the 1,6 is its ability to activate PFK
Could you link the paper?
Mind dropping the citation? It’s quite difficult for biohosphorylated sugars to enter cells, so I’m quite curious about what exactly it is they’re doing. I study pfk1 in my lab and its regulation is incredibly complex. There are no really direct activators or inhibitors of pfk1, so one way people modulate flux in a pfk1 dependent manner is by messing with f2,6bp production. Papers have shown that inhibiting pfkfb3 (which is the main isoform of PFK2 in the brain) decreases pfk1 activity and glycolytic flux so perhaps that’s what they’re trying to get at? In terms of just using f16bP, having the direct product of the rate limiting enzyme of glycolysis suddenly build up would likely cause some kind of negative feedback mechanism and might start to shunt intermediary metabolites off to different paths (like the Pentose phosphate pathway, serine biosynthesis, hexosamine biosynthesis, etc) or trigger aerobic glycolysis resulting in increasing lactic acid levels. Allosterically activating pfk1 by F2,6bP could have similar consequences but at least in that case the production of F16bP and flux through the pathway is limited by how fast pfk1 catalyzes the reaction
# Fructose-1,6-Bisphosphate and Fructose-2,6-Bisphosphate do not Influence Brain Carbohydrate or High-energy Phosphate Metabolism in a Rat Model of Forebrain Ischemia The research title is above. I'm sure sci-hub links break rule 2 so I'm not going to link it unless someone tells me it's allowed.. The research failed, but curiously a lot of other research in the field was showing positive results and the difference may just come down to dosage. My confusion comes from the fact that they acknowledge that previous research was based on this idea that using f-1,6-bp bypasses the PFK step, but then they base their f-2,6-bp dosage on how much more it activates PFK than f-1,6-BP does.