Fructose 2,6-bisphosphate glycolysis, regulatory

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. 

Phosphofructokinase-1 is a regulatory enzyme (Chapter 6), one of the most complex known. It is the major point of regulation in glycolysis. The activity of PFK-1 is increased whenever the cell s ATP supply is depleted or when the ATP breakdown products, ADP and AMP (particularly the latter), are in excess. The enzyme is inhibited whenever the cell has ample ATP and is well supplied by other fuels such as fatty acids. In some organisms, fructose 2,6-bisphosphate (not to be confused with the PFK-1 reaction product, fructose 1,6-bisphosphate) is a potent allosteric activator of PFK-1. The regulation of this step in glycolysis is discussed in greater detail in Chapter 15. 

This enzyme catalyses the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate (FBP) and is the key regulatory enzyme of glycolysis. The properties of phosphofructokinase (PFK) have been investigated in some detail in adult Moniezia expansa (60) and in plerocercoids of S. solidus (65), where its activity is modulated by a number of compounds, including ATP, AMP, fructose-6-phos-phate, Mg2 +, Mn2 +, K + and NH. In general, the PFKs from both species exhibit properties similar to those of the enzymes from mammalian sources and they probably regulate glycolysis in the same manner as their mammalian counterparts. The inhibitory effects of ATP on the PFK from Schistocephalus solidus and the relief of this inhibition by AMP are shown in Fig. 5.2. 

Other reciprocal regulators of glycolysis and gluconeogenesis are fructose-2,6-bisphosphate and acetyl-CoA. See Figure 16.7 for additional details about the reciprocal regulatory mechanisms of action of fructose-2,6-bisphophate. 

Oscillations were only observed when the initial substrate was a hexose, such as glucose 6-phosphate or fructose 6-phosphate, not fructose 1,6-bisphosphate or subsequent metabolites in the pathway. This indicates that that the enzyme responsible for the periodic behaviour is phosphofructokinase (PFK), which is the key regulatory enzyme for glycolysis. It catalyzes the irreversible transfer of a phosphate from ATP... 

EXAMPLE 13.10 Both the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate and the reverse-bypass of this reaction in gluconeogenesis are sensitive to the regulatory metabolite fructose 2,6-bisphosphate. This is not an intermediate in either glycolysis or gluconeogenesis but is formed by a separate ATP-dependent kinase, phosphofructokinase-2. 

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