Gluconeogenesis fructose 6-phosphate

Insufficient inorganic phosphate (especially in the liver cells of affected persons who ingest a large amount of fructose) impairs gluconeogenesis, protein synthesis, and energy production by oxidative phosphorylation. 

Fructose-2,6-bisphosphatase, a regulatory enzyme of gluconeogenesis (Chapter 19), catalyzes the hydrolytic release of the phosphate on carbon 2 of fructose 2,6-bisphosphate. Figure 7-8 illustrates the roles of seven active site residues. Catalysis involves a catalytic triad of one Glu and two His residues and a covalent phos-phohistidyl intermediate. 

Glucose 6-phosphate is an important compound at the junction of several metabolic pathways (glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogenosis, and glycogenolysis). In glycolysis, it is converted to fructose 6-phosphate by phosphohexose-isomerase, which involves an aldose-ketose isomerization. 

Fructose-1,6-bisphosphatase is an important rate-limiting step in gluconeogenesis. This gluconeogenic step antagonizes the opposite reaction that forms fructose-1, 6-bisphosphate from fmctose-6-phosphate and ATP... 

The interconversion of fructose-6-phosphate and fructose-1,6 bis phosphate is a control point in glycolysis and gluconeogenesis. Gluconeogenesis is a pathway which allows carbon atoms from substrates such as lactate, glycerol and some amino acids to be used for the synthesis of glucose, so it is in effect physiologically the opposite of... 

Two gluconeogenesis-specific phosphatases then successively cleave off the phosphate residues from fructose 1,6-bisphos-phate. In between these reactions lies the isomerization of fructose 6-phosphate to glucose 6-phosphate—another glycolytic reaction. 

Fructose 2,6-bisphosphate (Fru-2,6-bP) plays an important part in carbohydrate metabolism. This metabolite is formed in small quantities from fructose 6-phosphate and has purely regulatory functions. It stimulates glycolysis by allosteric activation of phosphofructokinase and inhibits gluconeogenesis by inhibition of fructose 1,6-bisphosphatase. 

The second glycolytic reaction that cannot participate in gluconeogenesis is the phosphorylation of fructose 6-phosphateby PFK-1 (Table 14-2, step ). Because this reaction is highly exergonic and therefore irreversible in intact cells, the generation of fructose 6-phosphate from fructose 1,6-bisphosphate (Fig. 14-16) is catalyzed by a different enzyme, Mg2+-dependent fructose 1,6-bisphosphatase (FBPase-1), which promotes the essentially irreversible hydrolysis of the C-l phosphate (not phosphoiyl group transfer to ADP) ... 

When fructose 2,6-bisphosphate binds to its allosteric site on PFK-1, it increases that enzyme s affinity for its substrate, fructose 6-phosphate, and reduces its affinity for the allosteric inhibitors ATP and citrate. At the physiological concentrations of its substrates ATP and fructose 6-phosphate and of its other positive and negative effectors (ATP, AMP, citrate), PFK-1 is virtually inactive in the absence of fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate activates PFK-1 and stimulates glycolysis in liver and, at the same time, inhibits FBPase-1, thereby slowing gluconeogenesis. 

Hydrolysis of fructose 1,6-bisphosphate by fructose 1,6-bispho -phatase bypasses the irreversible phosphofructokinase-1 reaction, and provides an energetically favorable pathway for the formation of fructose 6-phosphate (Figure 10.4). This reaction is an important regulatory site of gluconeogenesis. 

Gluconeogenesis Consumes ATP Conversion of Pyruvate to Phosphoenolpyruvate Requires Two High Energy Phosphates Conversion of Phosphoenolpyruvate to Fructose-1,6-bisphosphate Uses the Same Enzymes as Glycolysis... 

When fructose-6-phosphate is generated by gluconeogenesis or photosynthesis (see chapter 15), an equimolar amount of glucose-1-phosphate is usually removed from the hexose monophosphate pool by conversion to storage polysaccharide (glycogen in animals and many kinds of microorganisms starch in green plants). 

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