Fructose diphosphate monophosphate

Somewhat analogously, Lippich (1932) proposed to determine the amount of free aldehyde in solutions of sugars by measurements of extent of cyanhydrin formation, since this very rapid reaction should occur only between cyanide and free carbonyl it seems reasonable that a comparable factorial relationship exists here. Greater reactivity of glucose 6-phosphate with HCN than was experienced with glucose itself led Stepanov and Stepanenko (1937) to postulate the presence of more open chains in the derivative than in native glucose. These workers likewise explained (Stepanov and Stepanenko, 1940) the much more rapid reaction of fructose diphosphate than fructose monophosphate with HCN (30% vs. 13%) on the basis of a further shift to the open carbonyl. Underivatized fructose could not be induced to react under similar conditions. From their experi-... 

According to the conditions, hexose monophosphate and trehalose phosphate also accumulate in varying amounts. Separation of the fructose diphosphate from the monophosphate can be effected by precipitating the diphosphate with neutral lead acetate or barium ions, followed by precipitation of the monophosphate from the supernatant liquid with basic lead acetate or barium ions in 50% or stronger ethanol (199). The separation of the different monophosphates was carried out by fractional crystallization (200). Chromatographic methods have also been used (Chapter XI). 

This ester was first prepared 209) by partial hydrolysis of D-fructose diphosphate and later isolated by Robison 210) from the hexose monophosphate fraction obtained by yeast juice fermentation. 

The essentially nonreversible formation of D-fructose 1-phosphate in the muscle-aldolase system is probably attributable to thermodynamic stabilization. D-Fructose 1-phosphate can form a stable pyranose structure, whereas D-fructose 1,6-diphosphate can exist only in the less stable furanose or acyclic forms.72(,) Only when the cleavage products are removed is the monophosphate effectively split under the influence of aldolase. 

By the reaction of D-glyceraldehyde and 1,3-dihydroxypropane (both as monophosphate ester), D-fructose as the 1,6-diphosphate ester is formed. The process is readily reversible and is catalyzed by an enzyme known as aldolase. 

Figure 10.4 The abolition of positive cooperativity on the binding of allosteric effectors to some enzymes. Note the dramatic increases in activity at low substrate concentrations on the addition of adenosine monophosphate to isocitrate dehydrogenase, of deoxycytosine diphosphate to deoxythymidine kinase, and of fructose 1,6-diphosphate to pyruvate kinase this shows how the activity may be switched on by an allosteric effector (PEP = phosphoenolpyruvate). [From J. A. Hathaway and D. E. Atkinson, J. Biol. Chem. 238,2875 (1963) R. Okazaki and A. Kornbcrg, J. Biol. Chem. 239,275 (1964) R. Haeckel, B. Hess, W. Lauterhom, and K.-H. Wurster, Hoppe-Seyler s Z. Physiol. Chem. 349, 699 (1968).]...

A second phosphorylation reaction follows the isomerization step. Fructose 6-phosphate is phosphorylated by ATP to fructose 1,6-bisphosphate (F-1,6-BP). The prefix bis- in bisphosphate means that two separate monophosphate groups are present, whereas the prefix di- in diphosphate (as in adenosine diphosphate) means that two phosphate groups are present and are connected by an anhydride bond. 

Again in the first step of the reaction between 1,3-dihydroxyacetone monophosphate (5.41) and glyceraldehyde-3-phosphate catalysed by aldolase to form fructose-1,6-diphosphate or the reverse reaction, a ketimine (5.42) is formed between the substrate and the e-amino group of a Lys residue in the enzyme. The formation of this intermediate (5.42) can be demonstrated similarly by trapping it as a secondary amine using NaBH4 to reduce the ketimine. The glyceraldehyde-3-... 

The reaction is essentially irreversible under physiological conditions and is a major regulatory step of glycolysis. PFK-1 is an inducible, highly regulated, allosteric enzyme. In its active form, muscle PFK-1 is a homotetramer (M.W. 320,000) that requires K+ or NH4, the latter of which lowers Km for both substrates. When adenosine triphosphate (ATP) levels are low during very active muscle contraction, PFK activity is modulated positively despite low concentration of fructose-6-phosphate. Allosteric activators of muscle PFK-1 include adenosine monophosphate (AMP), adenosine diphosphate (ADP), fructose-6-phosphate, and inorganic phosphate (Pi) inactivators are citrate, fatty acids, and ATP. 

Glucose monophosphate has five possible isomeric forms with the -OPO3H groups being attached to C Cj, C3, C4 or Cg. Glucose diphosphate has 10 possible isomers with the phosphate groups attached to 1 2,1 3.1 4,1 6, 2 3, 2 4, 2 6, 3 4, 3 6 or 4 6 carbon atoms. Known fructose phosphates are 1 mono, 6 mono, 1 6 di and 2 6 di. 

A number of intermediates common to both the hexose monophosphate shunt and the glycolytic pathway are glucose-6-phosphate, fructose-6-phosphate, fructose-6,1-diphosphate, and triose phosphate. Thus, the two pathways can be expected to compete for intermediates, and, indeed, when a reconstituted glycolytic system made of purified enzymes is added to the reconstituted hexose monophosphate shunt, glucose oxidation by the shunt is inhibited by glycolysis. 

The erythrose 4-phosphate generated in the same step (Scheme 11.7) as the derivative of thiamine diphosphate is then available for enzyme-catalyzed aldol-type condensation with dihydroxyacetone monophosphate just as shown in Scheme 11.5 for the analogous reaction with glyceraldehyde 3-phosphate and using the same fructose-bisphosphate aldolase (EC 4.1.2.13). 

These reactions are catalyzed by kinases, some of viiich have already been discussed in this chapter. The reaction may be virtually irreversible as in phosphate ester formation. Here the phosphate acceptor may be a hydroi l group of a carbohydrate (glucose, ycerol, fructose, nucleotides, etc.), (Moline, or pantetheine. The terminal phosphate may also be transferred to an acceptor without loss of high chemical potential, such as to nucleoside mono- or diphosphate or to a nitro n atom. These reactions are freely reversible. Nucleotide diphosphate may also donate its terminal phosphate as in the nucleotide monophosphate kinase reaction. 

Fructose Monophosphate.— This ester has been obtained by Neuberg from the 1 6-diphosphate by partial hydrolysis. Unlike the diphosphate, it is fermented by yeast. Neuberg s ester is one of the two hexose phosphates found in muscle. 

---