Monosaccharides interconversions

We begin with an overview of the structures of glycoconjugates on cell surfaces (for more comprehensive reviews, see Refs. 2, 12-14, and 24). Next, the pathways of monosaccharide interconversions inside the cell are smnmarized, providing a framework for opportunities in unnatural monosaccharide metabolism. Specihc examples of modihed sugars and their effects on cells are then presented. Finally, the biosynthetic pathway of sialic acid is discussed with respect to its utility for cell surface oligosaccharide engineering. 

Figure 9 Monosaccharide interconversions in eukaryotic cells. Structures in squared boxes serve as exogenous substrates. Structures in rounded boxes are the activated monosaccharide donors. For simplicity, reactions are shown to progress in the forward direction.

Figure 5. The biosynthetic pathways of monosaccharide interconversions (printed with permission of Koch Light). 

Figure 13.1 Biosynthetic conversion of D-glucose into some of biologically important monosaccharides. The enzymes involved in these monosaccharide interconversions are transferases and isomerases. Nncleotide phosphoglycoses are synthesized as the glycose donors for biosynthesis of glycans. It is noted that 2-amino-2-deoxysugars (glycosamines) arise from D-fructose-6-phosphate and glutamine by the action of D-fmctose-6-phosphate L-glutamine transamidase with subsequent acetylation by acetyl coenzyme A...

The major pathways for sugar activation and monosaccharide interconversions are shown in Figure 1. 

The stmcture of monosaccharides is often written in the acycHc form although only very minor amounts of it ever occur in that form. Because the interconversions are rapid, the carbonyl groups of sugars can and do react both as if they are free and as if they are in a hemiacetal ring form. 

The phosphate esters and, to lesser extent, the sulphate esters of monosaccharides are very important naturally occurring derivatives. Metabolism of carbohydrates involves the formation and interconversion of a succession of monosaccharides and their phosphate esters of which glucose-1-phosphate and fruc-tose-6-phosphate are important examples. The sulphate esters of monosaccharides or their derivatives (usually esterified at carbon 6) are found in several polysaccharides, notably chondroitin sulphate, which is a constituent of connective tissues. 

The PPP has two chemical phases an initial irreversible oxidative phase when G6P is decarboxylated and oxidized to form ribulose-5-phosphate (Ru-5-P) followed by a more complicated but reversible non-oxidative phase involving interconversions of phosphorylated monosaccharides with four, five, six or seven carbon atoms. The... 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Monosaccharides have many structural variations that correspond to local minima that must be considered. Acyclic carbohydrates can rotate at each carbon, and each of the three staggered conformers is likely to correspond to a local minimum. The shapes of sugar rings also often vary. Furanose rings usually have two major local minima and a path of interconversion. Experimental evidence shows a clear preference for only one chair form for some pyranose rings, but others could exist in several conformers. For exanqple, the and conformers must all be considered as possible structures for L-iduronate, as discussed by Ragazzi et al. in this book. 

Figure 20-1 Some routes of interconversion of monosaccharides and of polymerization of the activated glycosyl units.

Several monosaccharides mentioned in this Section are present in polysaccharide chains not only as pyranoses but also as furanoses. From the biogenetic point of view, a furanosidic form of a monosaccharide must be considered to be an additional component, as no ready interconversions of cyclic forms may be expected for monosaccharide residues incorporated into oligosaccharide chains, or in the activated form used for their formation. 

In the mammal, complex polysaccharides which are susceptible to such treatment, are hydrolyzed by successive exposure to the amylase of the saliva, the acid of the stomach, and the disaccharidases (e.g., maltase, invertase, amylase, etc.) by exposure to juices of the small intestine. The last mechanism is very important. Absorption of the resulting monosaccharides occurs primarily in the upper part of the small intestine, from which the sugars are earned to the liver by the portal system. The absorption across die intestinal mucosa occurs by a combination of active transport and diffusion. For glucose, the aclive transport mechanism appears to involve phosphorylation The details are not yet fully understood. Agents which inhibit respiration (e.g., azide, fluoracetic acid, etc.) and phosphorylation (e.g., phlorizin), and those which uncouple oxidation from phosphorylation (e.g., dinitrophenol) interfere with the absorption of glucose. See also Phosphorylation (Oxidative). Once the various monosaccharides pass dirough the mucosa, interconversion of the other... 

Monosaccharides Are Related through a Network of Metabolic Interconversions... 

A selection of typical synthetic interconversions undergone by monosaccharides is contained in the following five sections (Sections 5.10.1 to 5.10.5). 

Gabriel O, van Lenten L (1978) The interconversion of monosaccharides. In Manners DJ (ed) International Review of Biochemistry Biochemistry of Carbohydrates II Vol 16. University Park Press, Baltimore, p 1... 

The present position with regard to the biological synthesis and interconversion of monosaccharides has been reviewed by L. Hough and J. K. N. Jones, Advances in Carbohydrate Chem., 11, 185 (1956). 

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). 

Alditols are often observed as the end-products of monosaccharide metabolism that are stored in various cellular and tissue compartments with low redox potentials. However, there are also examples of alditols as important metabolic intermediates allowing the interconversion of rare forms of certain monosaccharides. In enteric bacteria such as Escherichia coli the hexitol galactitol is taken up through enzyme II of the phosphoenol pyruvate-dependent phosphotransferase system and accumulated inside the cell as galactitol 1-phosphate. The genes involved in galactitol metabolism have been cloned on a 7.8 kb DNA fragment [201]. 

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