Monosaccharides metabolism

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]. 

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. 

Freeze HH. Monosaccharide metabolism. In Varki A, Cummings R, Esko J, Freeze H, Hart G, Marth J, eds. Essentials of Glycobiology, New York Coldspring Harbor Laboratory Press, 1999 69-84. 

All of the structures shown in Figures 7.2 and 7.3 are D-configurations, and the D-forms of monosaccharides predominate in nature, just as L-amino acids do. These preferences, established in apparently random choices early in evolution, persist uniformly in nature because of the stereospecificity of the enzymes that synthesize and metabolize these small molecules. 

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). 

Besides water, the diet must provide metabolic fuels (mainly carbohydrates and lipids), protein (for growth and turnover of tissue proteins), fiber (for roughage), minerals (elements with specific metabolic functions), and vitamins and essential fatty acids (organic compounds needed in small amounts for essential metabolic and physiologic functions). The polysaccharides, tri-acylglycerols, and proteins that make up the bulk of the diet must be hydrolyzed to their constituent monosaccharides, fatty acids, and amino acids, respectively, before absorption and utilization. Minerals and vitamins must be released from the complex matrix of food before they can be absorbed and utifized. 

Carbohydrates are aldehydes or ketones of higher polyhydric alcohols or components that yield these derivatives on hydrolysis. They occur naturally in plants (where they are produced photosynthetically), animals and microorganisms and fulfil various structural and metabolic roles. Monosaccharides are the simplest carbohydrates and they often occur naturally as one of their chemical derivatives, usually as components of disaccharides or polysaccharides. 

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. 

Fructose is found in honey and fruit and as part of the disaccharide sucrose (common table sugar). Sucrose is hydrolyzed by intestinal brush border sucrase, and the resulting monosaccharides, glucose and fructose, are absorbed into the portal blood. The liver phosphorylates frurtose and cleaves it into glyceraldehyde and DHAP. Smaller amounts are metabolized in renal proximal tubules. The pathway is shown in Figure 1-12-7 important enzymes to remember are ... 

In terms of function, polysaccharides fall into one of two groups structural and nutritional. For example, cellulose is a principal structural component of plants. Glycogen and starch, in contrast, are nutritional reservoirs for animals and plants, respectively. Monosaccharides may be mobilized from storage reservoirs such as glycogen and starch and then be metabolized to generate energy. 

The sugars (monosaccharides) occur in the metabolism in many forms (derivatives). Only a few important conversion reactions are discussed here, using D-glucose as an example. 

Esterification. The hydroxyl groups of monosaccharides can form esters with acids. In metabolism, phosphoric acid esters such as glucose 6-phosphate and glucose 1-phosphate (6) are particularly important. 

Carbohydrate metabolism. The liver takes up glucose and other monosaccharides from the plasma. Glucose is then either stored in... 

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt s excellent account of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers [methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85] acetals and ketals, pp. 85-92 modifications at C-1 [reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108] modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134. 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

Another Arabidopsis mutant, murl, which lacks the ability to synthesize 1-fucose, possesses a defective gene encoding GDP-d-Man-4,6-dehydratase, a key enzyme in 1-fucose biosynthesis. Further analysis revealed that 1-Fuc is replaced by 1-Gal, a structurally similar monosaccharide, in the cell walls of this mutant with no adverse effects on plant physiology or metabolism (Rayon et al, 1999). Transgenic plants containing this mutation can also be used for foreign protein production. 

Monosaccharides These carbohydrates, commonly referred to as sugars , contain from three to nine carhon atoms. Most common monosaccharides in nature possess five (pentose, C5H10O5) or six (hexose, C6H12O6) carhon atoms. For example, glucose, a six-carhon-containing sugar, is the most common monosaccharide that is metabolized in our body to provide energy, and fructose is also a hexose found in many fruits. 

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