Ribulose-5-phosphate isomerization

Scheme 11.9. A cartoon representation of the isomerization of xylulose 5-phospate to ribulose 5-phosphate through the common enol and catalyzed by ribulose-phosphate epimerase (EC 5.1.3.1).

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. 

In the pentose plu phatc pathway for degrading sugars, ribulose 5-phosphate is converted to ribose 5-phosphale. Propose a mechanism for the isomerization. 

Ribulose 5-phosphate is capable of a reversible isomerization to other pentose phosphates-xylulose 5-phosphate and ribose 5-phosphate. These reactions are catalyzed by two respective enzymes, viz., pentose-phosphate epimerase and pentose-phosphate isomerase, according to the scheme below ... 

These enzymes vary widely in secondary and tertiary structure.1273 Mannose-6-phosphate isomerase is a 45 kDa Zn2+-containing monomer. The larger 65 kDa L-fucose isomerase, which also acts on D-arabinose, is a hexameric Mn2+-dependent enzyme.1273 L-Arabinose isomerase of E. coli, which interconverts arabinose and L-ribulose, is a hexamer of 60-kDa subunits128 while the D-xylose isomerase of Streptomyces is a tetramer of 43-kDa subunits.129 The nonenzymatic counterpart of the isomerization catalyzed by the enzyme is the base-catalyzed Lobry deBruyn-Alberda van Ekenstein transformation (Eq. 13-25).130... 

In bacteria, which lack formate dehydrogenase, formaldehyde can be oxidized to C02 to provide energy beginning with the reactions of Eq. 17-51. The resulting fructose 6-P is isomerized to glucose 6-P, which is then dehydrogenated via Eq. 17-12 to form C02 and the regenerating substrate ribulose 5-phosphate. 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

Both transaldolase and transketolase require a ketose phosphate as the donor molecule and an aldose phosphate as the acceptor. Furthermore, both enzymes require the same steric configuration at carbons 3 and 4 as is found in glucose and fructose. Ribulose-5-phosphate, the first pentose phosphate to be formed in the pentose phosphate pathway, does not have the correct configuration to serve as a substrate for either transaldolase or transketolase. However, both a suitable donor ketose and an acceptor aldose can be made by isomerizations of ribulose-5-phosphate, and enzymes that... 

Stage 2 - Isomerization of ribulose 5-phosphate to ribose 5-phosphate... 

The ribulose 5-phosphate is now converted to ribose 5-phosphate by isomerization, a reaction catalyzed by phosphopentose isomerase ... 

D-Ribulose 5-phosphate then undergoes an isomerization by ribose-5-phosphate isomerase to o-ribose 5-phosphate (Step 4) ... 

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

Intermediates formed from G3P are utilized (Fig. 1) via a series of isomerizations, condensations and rearrangements resulting in the conversion of five molecules of triose phosphate to three of pentose phosphate, eventually ribulose 5-phosphate (Rbu-5-P). Phosphorylation of Rbu-5-P with ATP regenerates the original carbon acceptor Rbu-1,5-P2, thus completing the cycle. 

A more recently discovered second pathway starts from ribulose 5-phosphate (49) that is condensed with ammonia and glyceraldehyde phosphate or its isomerization product dihydroxy-acetone phosphate (50), which affords pyridoxal 5 -phosphate in a single enzyme-catalyzed reaction step (Fig. 5B) (28, 29). This pathway seems to be widely distributed it is used in plants (30) and has also been shown to proceed in fungi, archaea, and most eubacteria. 

Another group of sugar epimerases, which uses a metal cofactor instead of NADH/NAD+, takes an entirely different approach to epimerization. L-ribulose 5-phosphate 4-epimerase, which is involved in the bacterial metabolism of arabinose, performs a retro-aldol cleavage of a C-C bond to yield a metal-stabilized enolate of dihydroxyacetone and glycoaldehyde phosphate, similar to the reaction catalyzed by class II aldolases [77-79]. The glycoaldehyde phosphate is thought to rotate, such that addition of the enolate generates the isomeric product. 

The second stage involves isomerization reactions that convert ribulose-5-phosphate into ribose-5-phosphate or xylulose-5-phosphate. The pathway s name reflects the production of these phosphorylated five-carbon sugars (pentose phosphates). 

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