Ribose-5-phosphate, ketose-aldose

Now, finally, sedoheptulose 7-phosphate undergoes a transketolase-catalyzed (EC 2.2.1.2) process (as in Scheme 11.7) to remove two carbon atoms using the enzyme cofactor thiamine diphosphate to yield ribose 5-phosphate and a two-carbon fragment that has remained attached to the thiamine cofactor of transketo-lase (EC 2.2.1.1, sedoheptulose 7-phosphate) (Scheme 11.11). When the two-carbon fragment is added to glyceraldehyde 3-phosphate, the material of Scheme 11.8 again is applied and xylulose 5-phosphate results. The xylulose 5-phosphate isomerizes to ribulose 5-phosphate as in Scheme 11.9 (with intervention of ribulose phosphate 3-epimerase (EC 5.1.3.1). And, the ribose 5-phosphate, an aldose, isomerizes (an aldose-ketose isomerase, EC 5.3.1.6, ribose 5-phosphate isomerase) to ribulose 5-phosphate. 

One isomerization from the ketose to aldose Turns ribulose-5-phosphate to the phosphate of ribose. 

A recurring intermediate. Phosphopentose isomerase interconverts the aldose ribose 5-phosphate and the ketose ribulose 5-phosphate. Propose a mechanism. 

In the presence of formaldehyde (0.5 mol equiv.), sugar phosphates were formed in up to 45% yield, with pentose-2,4-diphosphates dominating over hexose triphosphates by a ratio of 3 1 (Scheme 13.2, Route B). The major component was found to be D,L-ribose-2,4-diphosphate with the ratios of ribose-, arabinose-, lyxose-, and xylose-2,4-diphosphates being 52 14 23 11, respectively. The aldomerization of 2 in the presence of H2CO is a variant of the formose reaction. It avoids the formation of complex product mixtures as a consequence of the fact that aldoses, which are phosphorylated at the C(2) position, cannot undergo aldose-ketose tautomerization. The preference for ribose-2,4-diphosphate 5 and allose-2,4,6-triphosphate formation might be relevant to a discussion of the origin of ribonucleic acids. 

TPP is also the coenzyme in the transketo-lase reaction (Fig. 8.27) found in the pentose phosphate pathway that interconverts hex-oses, pentoses, tetroses, and trioses. This reaction removes carbons 1 and 2 of a ketose and transfers them to an acceptor aldose. Examples include TPP transferring carbons 1 and 2 of xylulose-5-P to ribose-5-P, producing glyc-eraldehyde-3-P (5 carbons minus 2 carbons) and sedoheptulose-7-P (5 carbons plus 2 carbons). This reaction is reversible. A second reversible reaction has TPP transferring carbons 1 and 2 of xylulose-5-P to erythrose-4-P, producing fructose-6-P (4 carbons plus 2 carbons) and glyceraldehyde-3-P (5 carbons minus 2 carbons). 

Thiamine pyrophosphate is also an important cofactor for the transketolase reactions in the pentose phosphate pathway of carbohydrate metabolism (Fignre 15-3). These reactions are important in the reversible transformation of pentoses into the glycolytic intermediates fructose 6-phosphate and glyc-eraldehyde 3-phosphate. Again, it is the reactive carbon on the thiazole ring of TPP that reacts with a ketose phosphate (xylnlose 5-phosphate) to canse the release of an aldose phosphate with two fewer carbons (glyceraldehyde 3-phosphate). The TPP-bonnd glycoaldehyde unit is then transferred to a different aldose phosphate (ribose 5-phosphate or erythrose 4-phosphate) to produce a ketose phosphate that has two carbons more (sedoheptulose 7-phosphate or fructose 6-phosphate). 

This enzyme catalyzes the reversible transfer of the hydroxyketo group of a ketose phosphate to an aldose phosphate. The cofactor thiamine pyrophosphate (TPP) is associated with the enzyme and activates the ketose (Scheme 7). Most known donor ketoses (xylulose 5-phosphate, sedoheptulose 7-phosphate, fructose 6-phosphate, L-erythrose) have a trans arrangement of hydroxy groups at C-3 and C-4 hydroxypyruvate is an exception. A range of aldehydes (such as o-glyceraldehyde 3-phosphate, D-ribose 5-phosphate, o-erythrose 4-phosphate, glycoaldehyde) are acceptors. Transketolase has been... 

To generate ribose 5-phosphate from the oxidative pathway, the ribulose 5-phos-phate formed from the action of the two oxidative steps is isomerized to prodnce ribose 5-phosphate (a ketose-to-aldose conversion, similar to fmctose 6-phos-phate being isomerized to glncose 6-phosphate see section III.B.l below). The ribose 5-phosphate can then enter the pathway for nucleotide synthesis, if needed, or can be converted to glycolytic intermediates, as described below for the nonox-idative phase of the pentose phosphate pathway. The pathway through which the ribose 5-phosphate travels is determined by the needs of the cell at the time of its synthesis. 

Monosaccharides. M. are linear polyhydroxyalde-hydes (aldoses) or polyhydroxyketones (ketoses). Most important among M. are the pentoses (CjHiqO,) and hexoses (C6H,20 ). Important aldopentoses include, e.g., D- ribose, D- xylose, and L- arabinose. Important aldohexoses include D- glucose, D- man-nose, and D- galactose the major ketohexoses are D- fructose and sorbose. The 6- deoxy sugars L- fu-cose and L- L-rhamnose are also widely distributed hexoses. M. with more carbon atoms (heptoses 7 carbon atoms, octoses, etc.) or less carbon atoms (trioses 3 carbon atoms) do not occur in the free form in organisms but do play a role in carbohydrate metabolism as phosphate esters tetroses (4 carbon atoms) erythrose, threose are relatively rate. 

Transaldolation a reaction of carbohydrate metabolism, in which a C3-unit (equivalent to a dihy-droxyacetone unit) is transferred from a ketose to an aldose. T. is catalysed by transaldolase (EC 2.2.1.2). The C3-unit does not exist in the free state, but remains bound to the e-group of a lysine residue in the enzyme (Fig ). Only fructose 6-phosphate and sedoheptulose 7-phosphate are cleaved by transaldolase. Acceptors for the C3-unit are the aldose phosphates, o-glyceraldehyde 3-phosphate, D-erythrose 4-phosphate and more rarely ribose 5-phosphate. There is no coenzyme and the mechanism of reaction is similar to that of aldolase (EC 4.1.2.13). 

Transketolase (TK) is involved in anaerobic carbohydrate metabolisms such as the nonoxidative phase of the pentose phosphate pathway. In plants and photosynthetic bacteria, TK is involved in the Calvin-Benson cycle. TK catalyses the transfer of a 2-carbon dihydroxyethyl group from a ketose phosphate (donor substrate such as D-xylulose 5-phosphate) to the Cl position of an aldose phosphate (acceptor substrate such as o-ribose 5-phosphate) (Figure 4.3) (Schneider and Lindqvist 1998). The first product is an aldose phosphate released from the donor (such as glyceraldehyde 3-phosphate) and the second is a ketose phosphate (such as sedoheptulose 7-phosphate), in which the 2-carbon fragment is attached to the acceptor. Examples of the substrates and the products mentioned above are for the first reaction of the pentose phosphate pathway. In the second reaction of the same pathway, the acceptor is D-ery-throse 4-phosphate and the second product is o-fructose 6-phosphate. A snapshot X-ray crystallographic study revealed that an ot-carbanion/enamine a,p-dihydroxyethyl ThDP is formed as a key intermediate (Fiedler et al. 2002). Then, a nucleophilic attack of the a-carbanion intermediate on the acceptor substrate occurs. 

Several rare ketose 1-phosphates have been obtained by use of L-rhamnulose kinase on the corresponding ketoses which were, in turn, available by isomerization of the appropriate 2R- or 25-aldoses (D-ribose, L-lyxose, L-mannose, L-talose, D-glucose, D-allose, L-rhamnose, L-fucose) with L-rhamnose- or L-fucose-isomerase, respectively. P-L-Fucose 1-phosphate and the thermodynamically less stable p-anomer of GDP-fucose were accessible by use of enzymatic processes. A new, simple, chemical preparation of rhamnulose 1-phosphate from L-rhamnose is outlined in Scheme 5. ... 

Fig. 15.4 Reaction of transketolase. (a) Typical transketolase reaction. TPP is thiamine pyrophosphate bound in the enzyme. C-2 unit from fructose 6-phosphate (C6) is transferred to aldose phosphate (ribose 5-phosphate in the figure, C5) via TPP to produce shorto ketose (erythulose 4-phosphate, C4) and longer chain length ketose product (sedoheptulose 7-phosphate, C7). (b) Proposed reaction with 5KGA. C2 unit of 5KGA might be transferred to TPP in the enzyme as described in a. The remaining part of 5KGA is tartaric semialdehyde, which is oxidized by a certain enzyme in acetic acid bacteria to become L-tartaric acid. C2 unit attached on TPP might be transferred to aldose phosphate as in a, or released to form glycol aldehyde, which is oxidized to become glycolic acid...

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. 

The rate of hydrolysis is typical for each ester and has found use in analysis. Some esters such as those with the phosphate at the primary alcohol group and the polyalcohol phosphates are not appreciably hydrolyzed in i N acid at 100 in 7-10 min. These are usually classed as stable esters. Other phosphates such as the aldose i-phosphates are completely hydrolyzed under the above mentioned conditions. Ketose i-phosphates are partially hydrolyzed. Some phosphates such as the ribose and deox5nibose i-phosphates are so labile that their phosphate reacts as inoi anic phosphate in the usual methods of estimation. A review on the subject is available . 

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