Interconversion of Sugar Nucleotides

Neufield, E.F., V. Ginsburg, E.W. Putman, and D. Fanshier Formation and interconversion of sugar nucleotide by plant extract Arch. Biochem. Biophys. (1957) 602-616. 

Figures 2.10-2.15 summarise the major interconversions of sugar nucleotides currently postulated. For detailed references see reviews cited at the end of this chapter.

Figure 7.9 Interconversion of sugar phosphates and sugar nucleotide phosphates. Adapted from "Biotechnology of microbial exopolysaccharides". IW Sutherland, Cambridge University Press, 1990.

At about this time, Hassid was joined by V. Ginsburg and E. F. Neufeld, and an active program evolved dealing with the role of sugar nucleotides (glycosyl esters of nucleoside pyrophosphates) in the interconversion of carbohydrates in higher plants. In the initial studies, they were joined by P. K. Stumpf, who had been ap-... 

From this brief survey, it is seen that there were few features of carbohydrate metabolism in plants that escaped Hassid s touch, and much that we now know about the role of sugar nucleotides in the interconversion of carbohydrates in plants is a direct result of his persistent effort. From the incorporation of labelled precursors into monosaccharides, to the conversion of the monosaccharides into their glycosyl phosphates, to the action of the pyrophosphorylases in the synthesis of glycosyl esters of nucleoside pyrophosphates, to the interconversion of the resulting sugar nucleotides, to the polymerization of the activated monosaccharides to yield disaccharides and the homopolysaccharides, and, finally, to the modification of the polysaccharides by methylation—in summary, to almost every aspect... 

The several known enzymic mechanisms for the synthesis of sugar nucleotides have been previously reviewed. It was pointed out that the mechanism of epimerization, whereby the glycosyl moiety of the glycosyl ester of a nucleotide is transformed into one having a different group-configuration, was obscure. This process may be exemplified by one of the first such enzymic interconversions to be discovered ... 

The role of soluble, cytoplasmic enzymes in saccharide assembly seems chiefly to be in the phosphorylation of sugars and the interconversion of sugar phosphates. The enzymes of sugar nucleotide interconversion are generally membrane-associated and must, in most cases, be firmly membrane-bound. They are, therefore, likely to be integral membrane proteins and must, for the most part, be constituents of the endoplasmic reticulum. 

I. Pathways of Sugar Nucleotide Interconversion Further Reading... 

Swama Latha Y, Yathindra N (1992) Stereochemical studies on nucleic acid analogs. I. Conformations of a-nucleosides and a-nucleotides interconversion of sugar puckers via 04 -exo. Biopolymers 32 249-269... 

The repair and replication of cells involves metabolism - interconversions of hundreds of low molecular weight metabolites that ultimately yield the precursors for much larger, more complex macromolecules such as phospholipids (based on phosphatidic. acids or long chain fatty acid esters of glycerol phosphate), polynucleotides such as RNA and DNA (polymers of nucleotide monomers), proteins (polypeptides or amino acid monomers linked by peptide bonds) and polysaccharides (polymers of simple sugars or monosaccharides). 

In the nonoxidative phase, the pathway catalyzes the interconversion of three-, four-, five-, six-, and seven-carbon sugars in a series of nonoxidative reactions that can result in the synthesis of five-carbon sugars for nucleotide biosynthesis or the conversion of excess five-carbon sugars into intermediates of the glycolytic pathway. All these reactions take place in the cytosol. These interconversions rely on the same reactions that lead to the regeneration of ribulose 1,5-bisphosphate in the Calvin cycle. 

In the non-oxidative portion of the Pentose Phosphate Pathway a series of sugar interconversions takes the RU-5-P to intermediates of other pathways Ribose-5-P for nucleotide biosynthesis, and F-6-P and Ga-3-P for glycolysis/ gluconeogenesis. All of these reactions are near equilibrium, with fluxes driven by supply and use of the three intermediates listed above. 

Sugar skeletons are interconverted by way of three classes of compound, sugar phosphates, sugar nucleotides and cyclitols and the major known pathways which interconnect them are summarised in the schemes later in this chapter. The sugar nucleotides are the main intermediates in these interconversions and it is their metabolism which forms the bulk of this chapter. The cyclitols provide an important and, sometimes, dominant route from hexose to uronic acid and, thence, pentoses in plants, but their role in animals is unclear. Sugar phosphates are of importance as the entry to the sugar nucleotide pathways, but of themselves contribute little to metabolic interconversion directly for anabolic purposes. 

Several epimeric pairs of monosaccharides are produced by epimerization of nucleotide sugars (Luckner, 1990). For example, UDP-D-glucose-4-epimerase converts UDP-D-glu-cose to UDP-D-galactose. Enzymes that produce the other epimers are also known. A C-2 epimerase may be involved in the interconversion of D-glucose and D-mannose (Karr, 1976). 

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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