Fructoses gluconeogenesis

Glycogen breakdown Conversion of galactose and fructose Gluconeogenesis... 

As described in Chapter 19, Emile Van Schaftingen and Henri-Gery Hers demonstrated in 1980 that fructose-2,6-bisphosphate is a potent stimulator of phosphofructokinase. Cognizant of the reciprocal nature of regulation in glycolysis and gluconeogenesis. Van Schaftingen and Hers also considered the... 

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 2,6-Bisphosphate Plays a Unique Role in the Regulation of Glycolysis Gluconeogenesis in Liver... 

The free glucose produced by this reaction is supplied to the blood from the tissues. As exemplified by gluconeogenesis, one may easily envision the economical organization of these metabolic routes, since, apart from four special gluconeogenesis enzymes-pyruvate carboxylase, phosphopyruvate carboxylase, fructose bisphosphatase, and glucose 6-phosphatase-individual glycolytic enzymes are also used in the gluconeogenesis. 

In liver, cAMP activates gluconeogenesis, but in muscle, it activates glycolysis. Let s do liver first, and the muscle answer will just be the opposite. So, we want to activate gluconeogenesis in liver in response to increased phosphorylation (increased levels of cAMP). Phosphorylation of our enzyme (PFK-2) must have an effect that is consistent with the activation of gluconeogenesis. If gluconeogenesis is on and glycolysis is off, the level of fructose 2,6-bisphosphate (an activator of glycolysis) must fall. If fructose 2,6-bisphosphate is to fall, the PFK-2 that synthesizes it must be made inactive. So, in liver, phosphorylation of PFK-2 must inactivate the enzyme. 

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... 

Figure 6.22 Major precursors for gluconeogenesis. FBP is fructose 1,6-bisphosphate.

Fructose 2,6-bisphosphate is not a metabolic intermediate but an allosteric regulator. It has two important roles it increases the activity of PFK-1 but decreases the activity of fructose 1,6-bisphosphatase (FBPase). Consequently an increase in the concentration of fructose 2,6-bisphosphate favours glycolysis but restricts gluconeogenesis. 

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. 

The reaction catalyzed by fructose 1,6-bisphosphatase is an important regulation point in gluconeogenesis (see p. 158). 

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. 

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. 

The above-mentioned procedure for the synthesis of C-fructosides has been used to synthesize the bisphosphono analog of / -D-fructose 2,6-bisphos-phate [ 16], which is, as reported in Sect. 2.3, an important activator of glycolysis and inhibitor of gluconeogenesis. To prepare the target molecule we first attempted the conversion of the firee hy iroxyl group of 21 into an iodide which in turn can be easily converted into a phosphonate. However, this conversion... 

Fructose 1,6-biphosphatase Involved in gluconeogenesis inhibition by lithium of unknown relevance... 

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