Fructose 6-phosphate tautomerism

Glucose 6-phosphate is isomerized to fructose 6-phosphate by ring opening followed by a keto-enol tautomerization. 

Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which undergoes tautomerization to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bis-phosphate also be present, as well as 2 equivalents of Mg2+. One Mg2+ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion. 

Both D-[l- C]xylose and D-[5- C]arabinose were exposed to a concentrated phosphate buffer solution (pH 6.7). 1-Hydroxy-2-propanone (ace-tol) was distilled from the heated solution. Radioassay indicated that similar labeling [3- C] occurred in the acetol from both pentoses, with loss of the configurational difference thus, a 3-ketopentose or its enediol was suggested as an intermediate. Further work with 3-0- and 6-0-methyl-D-glucose and with 1-0-methyl-D-fructose indicated that /3-elimination from a 3-ketose or, in the case of a hexose, from a 3-ketose or a 4-ketose, or both, tautomerization of the resulting a-diketone to a /3-diketone, and hydrolytic cleavage are essential steps in the formation of acetol. 

Both the aldol and reverse aldol reactions are encountered in carbohydrate metabolic pathways in biochemistry (see Chapter 15). In fact, one reversible transformation can be utilized in either carbohydrate biosynthesis or carbohydrate degradation, according to a cell s particular requirement. o-Fructose 1,6-diphosphate is produced during carbohydrate biosynthesis by an aldol reaction between dihydroxyacetone phosphate, which acts as the enolate anion nucleophile, and o-glyceraldehyde 3-phosphate, which acts as the carbonyl electrophile these two starting materials are also interconvertible through keto-enol tautomerism, as seen earlier (see Section 10.1). The biosynthetic reaction may be simplihed mechanistically as a standard mixed aldol reaction, where the nature of the substrates and their mode of coupling are dictated by the enzyme. The enzyme is actually called aldolase. 

Glucose 6-phosphate is then isomerized to fructose 6-phosphate. This conversion of an aldose sugar to a ketose sugar is easy to rationalize in terms of keto-enol tautomerism (see Box 10.1). 

This is achieved by two keto-enol tautomerism reactions and a common enol (see Box 10.1). Mechanistically, it is identical to the isomerization of glucose 6-phosphate to fructose 6-phosphate seen earlier in the sequence, so we can move on to the next step of the pathway. 

Nucleophilic acyl substitution and tautomerization lead to the formation of glucosamine 6-phosphate from fructose 6-phosphate. The mechanism of opening of the fructofuranose ring was shown in the previous problem. 

Step 2 is an isomerization, in which the pyranose ring of glucose 6-phosphate opens, tautomerism causes isomerization to fructose 6-phosphate, and a furanose ring is formed. 

Phosphorylation and isomerization. Glucose, produced by the digestion of dietary carbohydrate., is first phosphorylated at the hydroxyl group on C6 by reaction with ATP in a process catalyzed by the enzyme hexokinase. The glucose 6-phosphate that results is isomerized by glucose 6-phosphate isomerase to fructose 6-phosphate. As the open-chain structures in Figure 29.4 show, this isomerization reaction takes place by keto-enol tautomerism (Section 22.1), since both glucose and fructose share a common enol ... 

One keto-enol tautomerism forms an enediol a second then forms the ketone carbonyl group in fructose 6-phosphate. (See Section 12.8A and Problems 12.34 and 12.35.) The conversion of the aldose to a ketose is necessary to facilitate the chemistry in Reaction 4. 

One pathway for the metabolism of D-glucose 6-phosphate is its enzyme-catalyzed conversion to D-fructose 6-phosphate. Show that this transformation can be accomplished as two enzyme-catalyzed keto-enol tautomerisms. 

Scheme 11.5. A cartoon representation of the catalyzed (fructose-bisphosphate aldolase, EC 4.1.2.13) aldol-type condensation between glyceraldehyde 3-phosphate and dihydroxyacetone monophosphate to produce the six-carbon ketosugar fructose-1,6-bisphosphate. An active site lysine Lys-NH2 [" H3NCH2CH2CH2CH2CH(NH3 )C02 ] apparently serves as the catalyst through addition at the carbonyl followed by proton tautomerization.

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