Monosaccharides phosphate esters

Monosaccharides also form phosphate esters with phosphoric acid. Monosaccharide phosphate esters are important molecules in biological system. For example, in the DNA and RNA nucleotides, phosphate esters of 2-deoxyribose and ribose are present, respectively. Adenosine triphosphate (ATP), the triphosphate ester at C-5 of ribose in adenosine, is found extensively in living systems. 

This probably explains the absence of anhydrides in the hydrolysis products of monosaccharide phosphate esters. 

Phosphate esters of glucose, fructose, and other monosaccharides are important metabolic intermediates, and the ribose moiety of nucleotides such as ATP and GTP is phosphorylated at the 5 -position (Figure 7.13). 

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. 

Many monosaccharides and their derivatives occur naturally in a form in which one or more of the hydroxyl groups has been substituted by a phosphate or a sulfate group. These are known as esters. In general, the phosphate esters are found as components of metabolic pathways within cells, whereas the sulfate esters are found in oligosaccharides and polysaccharides occurring outside cells. 

Two phosphate esters and two sulfate esters of monosaccharides that occur naturally are fructose 1,6-bisphosphate and 6-phosphogluconate (for both, see Chap. 11) and D-galactose 4-sulfate and N-acetylgalactosamine 4-sulfate. 

Phosphate Esters. An ester is formed by elimination of H20 and formation of a linkage between an acid and an alcohol (or phenol) (Fig. III-22). Phosphomonoesters, especially of monosaccharides, are very common (Fig. ffl-23). Because phosphoric acid is a tribasic acid, it can also form di- and triesters (Fig. III-24). Phosphotriesters are rarely found in nature, but diesters are extremely important, particularly as the fundamental linkage of the nucleic acid polymers, which are sequences of ri-bose (or deoxyribose) units linked by 3 —> 5 phos-phodiester bonds (see Fig. III-25). Like phosphoric acid, which has three dissociable protons (Fig. III-26), phosphomono- and phosphodiesters are acidic and typically ionize as shown in Fig. HI-27. Note the similarities between the pvalues for... 

Other Biological Phosphate Compounds. Elimination of water between phosphoric acid and certain other types of compounds results in formation of a variety of phosphate compounds that have properties that are different from simple phosphomonoesters. A phosphate ester of a monosaccharide in which phosphate is linked to the anomeric hydroxyl is called a phosphoacetal. An example is a-D-glucopyranosyl-1 -phosphate (glucose-1-phosphate) (Fig. III-28). A related group of compounds... 

Pathways in the formation of NDP-sugars. A seiection of monosaccharide conversions occurring at the phosphate ester and nucieotide-monosaccharide ievei in animais, piants and bacteria are shown all pathways radiate from fructose-6-phosphate, indicating the central role of this metabolite. The dTDP, GDP and UDP-yV-acetylmu-ramic pathways are peculiar to bacteria, whereas ADP-o-glucose, UDP-o-apiose and UDP-L-arabinose are found in plants. For reasons of simplicity, other pathways, e. g., to UDP-L-rhamnose in plants, GDP-o-rhamnose in Pseudomonas aeroginosa and GDP-o-arabinose in trypanosomatids are not included. The figure is reproduced from Chap. 6.4 of the first edition of this book... 

Lower monosaccharides, i.e., aldo- and keto-bioses, -trioses, and -tetroses, do not exist naturally in a free state. Glyceroaldehyde and hydroxyacetone in phospho-rylated forms are the products of alcoholic fermentation and glycolytic sequence. Erythrose and erythrulose also appear in phosphorylated forms in the pentose cycle of glucose, while ketopentose-ribulose can be found as its phosphate ester (Table 5.1). 

In contrast to other monosaccharides, activated sialic acid donors are biosynthesized from A -acetylmannosamine (ManNAc) or directly from sialic acids (Sia), including A-acetylneuraminic acid (NeuAc), via a more complex pathway (21). ManNAc is phosphorylated at the at the 6-hydroxyl group and condensed with phosphoenolpyruvate to give A -acetylneuraminic acid-9-phosphate (NeuAc-9-P). Phosphate ester hydrolysis is followed by direct condensation with CTP to give CMP-NeuAc (Figure 3). Sialic acids can intercept this pathway directly via enzymatic reaction with CTP. 

Phosphate esters of monosaccharides are important intermediates in the metabolism of carbohydrates and in the formation of nucleic acids. 

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. 

The central portion of the nucleotide is the monosaccharide, and it is always present as a five-membered ring, that is, as a furanoside. The heterocyclic base of a nucleotide is attached through an A -glycosidic linkage to Cl of the ribose or deoxyribose unit, and this linkage is always (3. The phosphate group of a nucleotide is present as a phosphate ester and may be attached at C5 or C3. (In nucleotides, the carbon atoms of the monosaccharide portion are designated with primed numbers, i.e., T, 2, 3, etc.)... 

The monosaccharides found in living systems are mostly mono- and di-phosphate esters. Of greatest importance in animal metabolism are the three esters (10.11), which also occur in plant life, particularly fruit (Chapter 12.3). They have high water solubilities and high acid strengths (Table 5.26). Individual glucose phosphates vary greatly in their hydrolytic behaviour (Chapter 5.6). 

Phosphate esters of monosaccharides are found in all hving cells, where they are intermediates in carbohydrate metabolism. Some common sugar phosphates are the following ... 

Several heterocyclic compounds, including purines and pyrimidines, can be coupled to monosaccharides at the anomeric carbon to form a ribonucleoside (or simply a nucleoside). The most common nucleosides are ribose and 2-deoxyribose derivatives containing adenine, guanine, cytosine, thymine, or uracil. The phosphate ester of a nucleoside is called a nucleotide 30, 31, 34, 51, 59,64,66. 

An example of a positively charged receptor that binds to phosphate esters of monosaccharides is 18 (Scheme 12). This compound contains three guanidiniocarbonyl pyrrole-derived substituents around the aromatic core, a building block introduced by the Schmuck group as a binding site for... 

The hydroxy groups of monosaccharides can behave as alcohols and react with acids to form esters. Esters formed from phosphoric acid and various monosaccharides are found in all cells, and some serve as important intermediates in carbohydrate metabolism. The structures of two representative phosphate esters are shown below ... 

Considerable attention is given to phosphate ester and related chemistry in Chapter 20. The aldolase-catalysed synthesis of monosaccharides by way of phosphate intermediates is covered in Chapter 2. 

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