Monosaccharides are polyhydroxy aldehydes or ketones; that is, they are molecules with more than one hydroxyl group (-OH), and a carbonyl group (C=O) either at the terminal carbon atom (aldose) or at the second carbon atom (ketose). The carbonyl group combines in aqueous solution with one hydroxyl group to form a cyclic compound (hemi-acetal or hemi-ketal). Monosaccharides are classified by the number of carbon atoms in the molecule; trioses have three, tetroses four, pentoses five, hexoses six, and heptoses seven.
Most contain five or six. The most important pentoses include xylose, found combined as xylan in woody materials; arabinose from coniferous trees; ribose, a component of ribonucleic acids and several vitamins; and deoxyribose, a component of deoxyribonucleic acid. Among the most important aldohexoses are glucose, mannose, and galactose; fructose is a ketohexose. Several derivatives of monosaccharides are important. Ascorbic acid (vitamin C) is derived from glucose.
Important sugar alcohols (alditols), formed by the reduction of (i. e. , addition of hydrogen to) a monosaccharide, include sorbitol (glucitol) from glucose and mannitol from mannose; both are used as sweetening agents. Glycosides derived from monosaccharides are widespread in nature, especially in plants. Amino sugars (i. e. , sugars in which one or two hydroxyl groups are replaced with an amino group, -NH2) occur as components of glycolipids and in the chitin of arthropods.
The most common naturally occurring monosaccharides are D-glucose, D-mannose, D-fructose, and D-galactose among the hexoses, and D-xylose and L-arabinose among the pentoses. In a special sense, D-ribose and 2-deoxy-D-ribose are ubiquitous because they form the carbohydrate component of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), respectively; these sugars are present in all cells as components of nucleic acids. Sources of some of the naturally occurring monosaccharides are listed in Table 2.
D-xylose, found in most plants in the form of a polysaccharide called xylan, is prepared from corncobs, cottonseed hulls, or straw by chemical breakdown of xylan. D-galactose, a common constituent of both oligosaccharides and polysaccharides, also occurs in carbohydrate-containing lipids, called glycolipids, which are found in the brain and other nervous tissues of most animals. Galactose is generally prepared by acid hydrolysis (breakdown involving water) of lactose, which is composed of galactose and glucose.
Since the biosynthesis of galactose in animals occurs through intermediate compounds derived directly from glucose, animals do not require galactose in the diet. In fact, in most human populations (Caucasoid peoples being the major exception) the majority of people do not retain the ability to manufacture the enzyme necessary to metabolize galactose after they reach the age of four, and many individuals possess a hereditary defect known as galactosemia and never have the ability to metabolize galactose.
D-glucose (from the Greek word glykys, meaning “sweet”), the naturally occurring form, is found in fruits, honey, blood, and, under abnormal conditions, in urine. It is also a constituent of the two most common naturally found disaccharides, sucrose and lactose, as well as the exclusive structural unit of the polysaccharides cellulose, starch, and glycogen. Generally, D-glucose is prepared from either potato starch or cornstarch. D-fructose, a ketohexose, is one of the constituents of the disaccharide sucrose and is also found in uncombined form in honey, apples, and tomatoes.
Fructose, generally considered the sweetest monosaccharide, is prepared by sucrose hydrolysis and is metabolized by man. Chemical reactions The reactions of the monosaccharides can be conveniently subdivided into those associated with the aldehydo or keto group and those associated with the hydroxyl groups. The relative ease with which sugars containing a free or potentially free aldehydo or keto group can be oxidized to form products has been known for a considerable time and once was the basis for the detection of these so-called reducing sugars in a variety of sources.
For many years, analyses of blood glucose and urinary glucose were carried out by a procedure involving the use of an alkaline copper compound. Because the reaction has undesirable features–extensive destruction of carbohydrate structure occurs, and the reaction is not very specific (i. e. , sugars other than glucose give similar results) and does not result in the formation of readily identifiable products–blood and urinary glucose now are analyzed by using the enzyme glucose oxidase, which catalyzes the oxidation of glucose to products that include hydrogen peroxide.
The hydrogen peroxide then is used to oxidize a dye present in the reaction mixture; the intensity of the colour is directly proportional to the amount of glucose initially present. The enzyme, glucose oxidase, is highly specific for -D-glucose. In another reaction, the aldehydo group of glucose reacts with alkaline iodine to form a class of compounds called aldonic acids. One important aldonic acid is ascorbic acid (vitamin C, see structure), an essential dietary component for man and guinea pigs.
The formation of similar acid derivatives does not occur with the keto sugars. Either the aldehydo or the keto group of a sugar may be reduced (i. e. , hydrogen added) to form an alcohol; compounds formed in this way are called alditols, or sugar alcohols. The product formed as a result of the reduction of the aldehydo carbon of D-glucose is called sorbitol (D-glucitol). D-glucitol also is formed when L-sorbose is reduced. The reduction of mannose results in mannitol, that of galactose in dulcitol.
Sugar alcohols that are of commercial importance include sorbitol (D-glucitol), which is commonly used as a sweetening agent, and D-mannitol, which is also used as a sweetener, particularly in chewing gums, because it has a limited water solubility and remains powdery and granular on long storage. Formation of glycosides The hydroxyl group that is attached to the anomeric carbon atom (i. e. , the carbon containing the aldehydo or keto group) of carbohydrates in solution has unusual reactivity, and derivatives, called glycosides, can be formed; glycosides formed from glucose are called glucosides.
It is not possible for equilibration between the – and -anomers of a glycoside in solution (i. e. , mutarotation) to occur. The reaction by which a glycoside is formed (see below) involves the hydroxyl group (-OH) of the anomeric carbon atom (numbered 1) of both and forms of D-glucose– and forms of D-glucose are shown in equilibrium in the reaction sequence–and the hydroxyl group of an alcohol (methyl alcohol in the reaction sequence); methyl -D-glucosides and -D-glucosides are formed as products, as is water.
Among the wide variety of naturally occurring glycosides are a number of plant pigments, particularly those red, violet, and blue in colour; these pigments are found in flowers and consist of a pigment molecule attached to a sugar molecule, frequently glucose. Plant indican (from Indigofera species), composed of glucose and the pigment indoxyl, was important in the preparation of indigo dye before synthetic dyes became prevalent. Of a number of heart-muscle stimulants that occur as glycosides, digitalis is still used.
Other naturally occurring glycosides include vanillin, which is found in the vanilla bean, and amygdalin (oil of bitter almonds); a variety of glycosides found in mustard have a sulfur atom at position 1 rather than oxygen. A number of important antibiotics are glycosides; the best known are streptomycin and erythromycin. Glucosides–i. e. , glycosides formed from glucose–in which the anomeric carbon atom (at position 1) has phosphoric acid linked to it, are extremely important biological compounds.
For example, -D-glucose-1-phosphate (see formula), is an intermediate product in the biosynthesis of cellulose, starch, and glycogen; similar glycosidic phosphate derivatives of other monosaccharides participate in the formation of naturally occurring glycosides and polysaccharides. The hydroxyl groups other than the one at the anomeric carbon atom can undergo a variety of reactions, several of which deserve mention.
Esterification, which consists of reacting the hydroxyl groups with an appropriate acidic compound, results in the formation of a class of compounds called sugar esters. Among the common ones are the sugar acetates, in which the acid is acetic acid. Esters of phosphoric acid and sulfuric acid are important biological compounds; glucose-6-phosphate, for example, plays a central role in the energy metabolism of most living cells, and D-ribulose 1,5-diphosphate is important in photosynthesis.
Formation of methyl ethers Treatment of a carbohydrate with methyl iodide or similar agents under appropriate conditions results in the formation of compounds in which the hydroxyl groups are converted to methyl groups (-CH3). Called methyl ethers, these compounds are employed in structural studies of oligosaccharides and polysaccharides because their formation does not break the bonds, called glycosidic bonds, that link adjacent monosaccharide units.
In the reaction sequence shown, a segment of a starch molecule, consisting of three glucose units, is indicated; the Haworth formulation used to represent one of the glucose units shows the locations of the glycosidic bonds and the -OH groups. When complete etherification of the starch molecule is carried out, using methyl iodide, methyl groups become attached to the glucose molecules at the three positions shown in the methylated segment of the starch molecule; note that the glycosidic bonds have not been broken by the reaction with methyl iodide.
When the methylated starch molecule then is broken down (hydrolyzed), hydroxyl groups are located at the positions in the molecule previously involved in linking one sugar molecule to another, and a methylated glucose, in this case named 2,3,6 tri-O-methyl-D-glucose, forms. The linkage positions (in the example, at carbon atoms 1 and 4; the carbon atoms are numbered in the structure of the methylated glucose), which are not methylated, in a complex carbohydrate can be established by analyzing the locations (in the example, at carbon atoms 2, 3, and 6) of the methyl groups in the monosaccharides.
This technique is useful in determining the structural details of polysaccharides, particularly since the various methylated sugars are easily separated by techniques involving gas chromatography, in which a moving gas stream carries a mixture through a column of a stationary liquid or solid, the components thus being resolved. When the terminal group (CH2OH) of a monosaccharide is oxidized chemically or biologically, a product called a uronic acid is formed.
Glycosides that are derived from D-glucuronic acid (the uronic acid formed from D-glucose) and fatty substances called steroids appear in the urine of animals as normal metabolic products; in addition, foreign toxic substances are frequently converted in the liver to glucuronides before excretion in the urine. D-glucuronic acid also is a major component of connective tissue polysaccharides, and D-galacturonic acid and D-mannuronic acid, formed from D-galactose and D-mannose, respectively, are found in several plant sources.
Other compounds formed from monosaccharides include those in which one hydroxyl group, usually at the carbon at position 2 (see formulas for D-glucosamine and D-galactosamine), is replaced by an amino group (-NH2); these compounds, called amino sugars, are widely distributed in nature. The two most important ones are glucosamine (2-amino-2-deoxy-D-glucose) and galactosamine (2-amino-2-deoxy-D-galactose). Neither amino sugar is found in the uncombined form. Both occur in animals as components of glycolipids or polysaccharides; e. g. , the primary structural polysaccharide (chitin) of insect outer skeletons and various blood-group substances.
In a number of naturally occurring sugars, known as deoxy sugars, the hydroxyl group at a particular position is replaced by a hydrogen atom. By far the most important representative is 2-deoxy-D-ribose (see formula), the pentose sugar found in deoxyribonucleic acid (DNA); the hydroxyl group at the carbon atom at position 2 has been replaced by a hydrogen atom. Other naturally occurring deoxy sugars are hexoses, of which L-rhamnose (6-deoxy-L-mannose) and L-fucose (6-deoxy-L-galactose) are the most common; the latter, for example, is present in the carbohydrate portion of blood-group substances and in red-blood-cell membranes.
Disaccharides and oligosaccharides Disaccharides are a specialized type of glycoside in which the anomeric hydroxyl group of one sugar has combined with the hydroxyl group of a second sugar with the elimination of the elements of water. Although an enormous number of disaccharide structures are possible, only a limited number are of commercial or biological significance. Sucrose and trehalose Sucrose, or common table sugar, has a world production amounting to well over 10,000,000 tons annually.
The unusual type of linkage between the two anomeric hydroxyl groups of glucose and fructose (see formula, in which the asterisk indicates anomeric carbon atom) means that neither a free aldehydo group (on the glucose moiety) nor a free keto group (on the fructose moiety) is available to react unless the linkage between the monosaccharides is destroyed; for this reason, sucrose is known as a nonreducing sugar. Sucrose solutions do not exhibit mutarotation, which involves formation of an asymmetrical centre at the aldehydo or keto group.
If the linkage between the monosaccharides composing sucrose is broken, the optical rotation value of sucrose changes from positive to negative; the new value reflects the composite rotation values for D-glucose, which is dextrorotatory (+52), and D-fructose, which is levorotatory (-92). The change in the sign of optical rotation from positive to negative is the reason sucrose is sometimes called invert sugar. The commercial preparation of sucrose takes advantage of the alkaline stability of the sugar, and a variety of impurities are removed from crude sugarcane extracts by treatment with alkali.
After this step, syrup preparations are crystallized to form table sugar. Successive “crops” of sucrose crystals are “harvested,” and the later ones are known as brown sugar. The residual syrupy material is called either cane final molasses or blackstrap molasses; both are used in the preparation of antibiotics, as sweetening agents, and in the production of alcohol by yeast fermentation. Sucrose is formed following photosynthesis in plants by a reaction in which sucrose phosphate first is formed. The disaccharide trehalose is similar in many respects to sucrose but is much less widely distributed.
It is composed of two molecules of -D-glucose and is also a nonreducing sugar. Trehalose is present in young mushrooms and in the resurrection plant (Selaginella); it is of considerable biological interest because it is also found in the circulating fluid (hemolymph) of many insects. Since trehalose can be converted to a glucose phosphate compound by an enzyme-catalyzed reaction that does not require energy, its function in hemolymph may be to provide an immediate energy source, a role similar to that of the carbohydrate storage forms (i. e. , glycogen) found in higher animals.