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The absence of fructokinase results in the inability to phosphorylate fructose to fructose-1-phosphate within the cell. As a result, fructose is neither trapped within the cell nor directed toward its metabolism. [11] Free fructose concentrations in the liver increase and fructose is free to leave the cell and enter plasma.
The glucose-6-phosphate so produced can enter glycolysis after the first control point. In the second regulated step (the third step of glycolysis), phosphofructokinase converts fructose-6-phosphate into fructose-1,6-bisphosphate, which then is converted into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
Fru-2,6-P 2 strongly activates glucose breakdown in glycolysis through allosteric modulation (activation) of phosphofructokinase 1 (PFK-1).Elevated expression of Fru-2,6-P 2 levels in the liver allosterically activates phosphofructokinase 1 by increasing the enzyme’s affinity for fructose 6-phosphate, while decreasing its affinity for inhibitory ATP and citrate.
Fructose must undergo certain extra steps in order to enter the glycolysis pathway. [2] Enzymes located in certain tissues can add a phosphate group to fructose. [12] This phosphorylation creates fructose-6-phosphate, an intermediate in the glycolysis pathway that can be broken down directly in those tissues. [12]
Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. [1]
In gluconeogenesis glyceraldehyde-3-phosphate is reduced to fructose 1,6-bisphosphate with aldolase. In glycolysis fructose 1,6-bisphosphate is made into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate through the use of aldolase. The aldolase used in gluconeogenesis and glycolysis is a cytoplasmic protein.
Metabolism of fructose thus essentially results in intermediates of glycolysis. This means that fructose has the same fate as glucose after it gets metabolised. The final product of glycolysis (pyruvate) may then undergo gluconeogenesis, enter the TCA cycle or be stored as fatty acids.
Glycolysis preparatory phase −2 Phosphorylation of glucose and fructose 6-phosphate uses two ATP from the cytoplasm. Glycolysis pay-off phase 4 Substrate-level phosphorylation 2 NADH 3 or 5 Oxidative phosphorylation: Each NADH produces net 1.5 ATP (instead of usual 2.5) due to NADH transport over the mitochondrial membrane