Ketoses, interconversion with aldoses

D-xylose was converted into 2-furaldehyde in acidified, tritiated water, no carbon-bound isotope was detected. This suggested that the 1,2-enediol (2) reacted immediately, as otherwise, tritium would have been detected at the aldehydic carbon atom of 2-furaldehyde, as a result of aldose-ketose interconversion.An acidic dehydration performed with d-[2- H]xylose showed that an intramolecular C-2-C-1 hydrogen transfer had actually occurred. Thus, these data indicated that an intramolecular hydride shift is more probable than the previously accepted step involving a 1,2-enediol intermediate. 

The interconversion of aldoses and the respective 2-ketoses in alkaline solution may be somewhat more complex than originally supposed, as it has been reported that a partial transfer of hydrogen from C-2 of the aldose to C-l of the corresponding ketose occurs during the reaction.29 This observation is not inconsistent with isomerizations that involve 1,2-enediol intermediates. The transfer could occur as a result of a rapid conversion in which some of the protons originally at C-2 of the aldose molecules are retained by the solvent cage that surrounds the intermediate 1,2-enediol, and are, therefore, available for addition to C-l of the resulting ketose. It should be noted that other interpretations, such as hydride-transfer mechanisms, are also possible. 

The rearrangement is of interest because the corresponding enzymatic interconversion of aldoses and ketoses is an important part of the biosynthetic, photosynthetic, and metabolic pathways, as we shall see in Section 20-9. Although the biochemical rearrangement also may proceed by way of enediol intermediates, it is highly stereospecific and yields only one of two possible stereoisomeric aldoses. For example, glucose, but not mannose, can be enzymatically interconverted with fructose as the 6-phosphate ester derivative ... 

Non-enzymic aldose-ketose isomerisations that are acid catalysed appear to involve a 1,2-hydride shift. During acid-catalysed rearrangement of glucose to fructose, the label of [2- H]glucose substrate is retained in the [l- H]fructose product, distributed equally between the proR and proS positions." In the reverse sense retention of the label of tritiated fructose in the glucose and mannose products was not complete. Similar observations were made for the xylose-xylulose interconversion." With an appropriate sugar configuration (ribose), even the base-catalysed reaction proceeds partly with retention of label, presumably by the same mechanism as with trioses. 

The influence, on the reaction, of different substituents in the phenyl-hydrazine molecule and the specificity due to these molecular changes have been studied. The specificity in respect to certain aldose configurations was proved, and it was also shown that D-fructose and other 2-ketoses react with such weakly basic hydrazines as (p-bromo-, (p-carboxy-, (p-carbeth-oxy- and (p-nitro-phenyl)hydrazine. Correlations between the reaction rate and ease of interconversion between cyclic and acyclic forms were also determined. Studies with tritium-labeled D-fructose showed that the... 

Many of the mechanistic aspects of glucose isomerase catalysed aldose-ketose interconversion have been under discussion for some time and are still not fully understood. By comparison with triose phosphate isomerase (TIM, EC 5.3.1.1) and glucose 6-phosphate isomerase (EC 5.3.1.9), the base-catalysed formation of an 1,2-enediol was invoked as the key step of the epimerisation based on the work of Rose and co-workers with tritium-labelled substrates [26]. An unexplained featme of the epimerisation process was that in contrast to isomerisations with triose phosphate isomerase no proton exchange with the medium could be observed with D-xylose isomerase, a fact that was attributed to the phosphate group of the former as a mediator for the exchange process [26]. Subsequently, additional important differences between triose phosphate isomerase and xylose isomerase were recognised. For example, D-xylose isomerase is appar-endy a very slow enzyme catalysing about five molecules per second per active site with an absolute requirement for divalent cations, while TIM does not need co-factors and operates at nearly 1000-fold the speed of D-xylose isomerase at... 

L-Fucose isomerase catalyzes the interconversion of L-fucose to L-fuculose and o-arabinose to D-ribulose. It has neither sequence nor structural similarity with the other aldose-ketose isomerases. A crystal structure of the E. coli enzyme with an L-fucitol bound in the active site shows that the active site is located in a 20 A deep pocket, at the bottom of which is a single Mn ion. Mn is bound to Oi and O2 of L-fucitol the side chains of a monodentate Glu-337, a bidentate Asp-361 (with long bonds to both oxygens), His-528 and a water molecule. ... 

While DHAP aldolases produce ketose derivatives, access to biologically important and structurally more diverse aldose isomers is achievable by use of enzymatic ketol isomerase interconversions. For this purpose, we had previously shown that L-rhamnose isomerase (Rhal E.C. 5.3.1.14) and L-fucose isomerase (Fuel E.C. 5.3.1.3) from E. coli display a relaxed substrate tolerance. Both enzymes convert sugars and their derivatives with distinct stereopreference at C2 and common (3R)-OH configuration, but tolerate alterations in configuration or substitution pattern at subsequent positions of the chain (Scheme 2.2.5.5) [11, 12]. 

PMI from the fungus Candida albicans is a metalloenzyme of 48.7 kDa, which catalyzes the interconversion of phosphofructose and phosphomannose. The structure of this enzyme is different from that of rabbit PGI (with an a// -fold and not a metalloenzyme) and those of the few metallo-(phospho-)ketose/aldose isomerases discussed in... 

When an aldose or ketose is dissolved in water, a complex equilibrium may be established. The present article deals with the reactions involved and the rates of interconversion of the molecular species... 

An immediately applicable example was the interconversion of 2-ketoses and 2-C-(hydroxymethyl)aldoses predictable from the analysis of the mechanism of the primary process of the Bilik reaction (Scheme 4). However, the primary studies performed with hex-2-uloses [47] and pent-2-uloses [48] did not provide results consistent with those expected according to the mechanism revealed later, as no 2-C-(hydroxymethyl)aldose was detected in the reaction mixtures. Based on the results of the primary studies, as well as on the assumption that the thermodynamic equilibrium of a pertinent 2-ketose and 2-C-(hydroxyme-thyl)aldose might be shifted totally in favor of the former, the investigation of the interconversion was approached from the side of the latter sugar. Some inspiration might be provided also by the analytical studies of the transformation of 2-ketoses to the corresponding 2-C-(hydroxymethyl)aldoses catalyzed by nickel(II)-ethylenediamine complexes [49] (see Osanai,this voL). 

Based on the results of studies with isotopically substituted D-fructoses, and following the stereochemical rules of molybdate complexes, the mechanism of the molybdic acid catalyzed mutual interconversion of 2-ketoses and 2-C-(hydroxymethyl)aldoses (referred to as the primary process) [54,55] is shown in Scheme 11. 

In cases where a 2-C-(hydroxymethyl)aldose is easily available via base-catalyzed aldolization of a 2,3-0-alkylidene-aldofuranose with formaldehyde, the carbon-skeleton rearrangement operating in the Bilik reaction can also be conveniently exploited for preparation of 2-ketoses. The method is especially advantageous for synthesis of heptuloses and octuloses as (1) in special cases the 2-C-hydroxymethyl side chain construction is simpler than the classical aldose chain elongations, and (2) the equilibrium of a 2-C-(hydroxymethyl)aldose and its corresponding 2-ketose in the Bilik interconversion is much more favorably shifted to the side of the latter sugar (always > 85%) than the LdB-AvE transformation of the pertinent unbranched aldose. 

It is well known that aldoses are susceptible to epimerization along with isomerization under alkaline conditions. The equilibrium between glucose, mannose and fructose in an alkaline media is the best-known example of such a case. This results in the interconversion of two aldoses and the corresponding constitutionally isomeric ketose is an equilibrium mixture of the three [41]. An aldose is... 

The extension of the unique, stereospecific carbon-skeleton rearrangement of epimeric aldoses that occurs during the Bilik reaction to produce 2-ketoses and 2-C-(hydroxymethyl)aldoses has provided new, one-step preparative procedures of representatives of both these groups of reducing sugars by simple mutual interconversions. In accordance with the epimeric aldoses ratio representation of the Bilik reaction equilibria, the pertinent ratios of the interconverting sugars at their thermodynamic equilibria are as follows ... 

Tissues which are more active in the synthesis of lipids than nucleotides require NADPH rather than ribose moieties. In such tissues, e.g. adipose tissue, the ribose 5-phosphate enters a series of sugar interconversion reactions which connect the pentose phosphate pathway with glycolysis and gluconeogenesis. These interconversion reactions constitute the non-oxidative phase of the pathway (Figure 11.14) and since oxidation is not involved, NADPH is not produced. Two enzymes catalyse the important reactions transketolase which contains thiamin diphosphate (Figure 12.3a) as its prosthetic group and transaldolase. Both enzymes function in the transfer of carbon units transketolase transfers two-carbon units and transaldolase transfers three-carbon units. The transfer always occurs from a ketose donor to an aldose acceptor. The interconversion sequence requires the oxidative phase to operate three times, i.e. three molecules of glucose 6-phosphate yield three molecules of ribulose 5-phosphate. 

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