Carbohydrates. Classification, structure and chemical properties of mono-, di-, oligo- and polysaccharides.
Chemical properties of monosaccharides.
Introduction: Carbohydrates are the most abundant class of bioorganic molecules on planet Earth. Although their abundance in the human body is relatively low, carbohydrates constitute about 75% by mass of dry plant materials.
Green (chlorophyll-containing) plants produce carbohydrates via photosynthesis. In this process, carbon dioxide from the air and water from the soil are the reactants, and sunlight absorbed by chlorophyll is the energy source.
Plants have two main uses for the carbohydrates they produce. In the form of cellulose, carbohydrates serve as structural elements, and in the form of starch, they provide energy reserves for the plants.
Dietary intake of plant materials is the major carbohydrate source for humans and animals. The average human diet should ideally be about two-thirds carbohydrate by mass.
Carbohydrates have the following functions in humans:
1. Carbohydrate oxidation provides energy.
2. Carbohydrate storage, in the form of glycogen, provides а short- term energy reserve.
3. Carbohydrates supply carbon atoms for the synthesis of other biochemical substances (proteins, lipids, and nucleic acids).
4. Carbohydrates form part of the structural framework of DNA and RNA molecules.
5. Carbohydrate “markers” on cell surfaces play key roles in cell -cell recognition processes.
Carbohydrate classifications
Most simple carbohydrates have empirical formulas that fit the general formula СnН2nОn. An early observation by scientists that this general formula can also be written as Сn(Н2О)n is the basis for the term carbohydrate – that is, “hydrate of carbon.” It is now known that this hydrate viewpoint is not correct, but the term carbohydrate still persists. Today the term is used to refer to an entire family of compounds, only some of which have the formula СnН2nОn.
Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield such substances upon hydrolysis. The carbohydrate glucose is а polyhydroxy aldehyde, and the carbohydrate fructose is а polyhydroxy ketone.
А striking structural feature of carbohydrates is the large number of functional groups present. In glucose and fructose there is а functional group attached to each carbon atom. Carbohydrates are classified on the basis of molecular size as monosaccharides, oligosaccharides, and polysaccharides.
Monosaccharides are carbohydrates that contain a single polyhydroxy aldehyde or polyhydroxy ketone unit. Monosaccharides cannot be broken down into simpler units by hydrolysis reactions. Both glucose and fructose are monosaccharides. Naturally occurring monosaccharides have4rom three to seven carbon atoms; five- and six-carbon species are especially common. Pure monosaccharides are water-soluble, white, crystalline solids.
Oligosaccharides are carbohydrates that contain from two to ten monosaccharide units. Disaccharides are the most common type of oligosaccharide.Disaccharides are carbohydrates composed of two monosaccharide units covalently bonded to each other. Like monosaccharides, disaccharides are crystalline, water-soluble substances. Sucrose (table sugar) and lactose (milk sugar) are disaccharides.
Within the human body, oligosaccharides are often found associated with proteins and lipids in complexes that have both structural and regulatory functions. Free oligosaccharides, other than disaccharides, are seldom encountered in biological systems.
Complete hydrolysis of an oligosaccharide produces monosaccharides. Upon hydrolysis, а disaccharide produces two monosaccharides, а trisaccharide three monosaccharides, а hexasaccharide six monosaccharides, and so on.
Polysaccharides are carbohydrates made up of many monosaccharide units. Polysaccharides, which are polymers, often consist of tens of thousands of monosaccharide units. Both cellulose and starch are polysaccharides. We encounter these two substances everywhere. The paper on which this book is printed is mainly cellulose, as are the cotton in our clothes and the wood in our houses. Starch is а component of many types of foods including bread, pasta, potatoes, rice, corn, beans, and peas.
Chirality: handedness in molecules
Before considering structures for and reactions of specific carbohydrates, we will consider handedness, а biologically important structural property exhibited by most carbohydrates. Most carbohydrate molecules can exist in two forms – а left-handed form and а right-handed form. Significantly, these different forms often elicit different responses within the human body.
Mirror Images. The concept of mirror images is the key to understanding molecular handedness. All objects, including all molecules, have mirror images. Themirror image of an object is the object’ reflection in а mirror. For example: human hands.
Chirality. Objects that cannot be superimposed upon their mirror image are said to be chiral objects. А chiral object is an object that is not identical to its mirror image. Your hands and feet are chiral objects, as are gloves and shoes. Objects that can be superimposed upon their mirror images are achiral. An achiral object is identical to its mirror image. Achiral objects include tube socks, solid-colored ties and Т-shirts.
Molecules, like larger objects, can be chiral or achiral. А simple example of а chiral molecule is the trisubstituted methane bromochloroiodomethane.
The simplest example of а chiral carbohydrate is the three-carbon molecule glyceraldehyde.
Trying to superimpose the mirror image of а molecule on that molecule visually, is one way to determine molecular chirality. Another method, which is much easier to apply, makes use of the observation that generally, whenever а carbon atom in а molecule is bonded to four different groups, the molecule as а whole is chiral.
Any organic molecule containing а single carbon atom with four different groups attached to it exhibits chirality. Such а carbon atom is called а chiral center. Аchiral center is an atom in а molecule that has four different groups tetrahedrally bonded to it.
Chiral centers within molecules are often denoted by а small asterisk. Note the chiral centers in the following molecules.
2-butanol 1-chloto-1-iodoethane 3-methylhexane
Organic molecules, especially carbohydrates, may contain more than one chiral center. For example, the following carbohydrate has two chiral centers.
Stereoisomers are isomers whose atoms are connected in the same way but differ in their arrangement in space. The two nonsuperimposable mirror-image forms of а chiral molecule are stereoisomers.
There are two major causes of stereoisomerism: (1) the presence of а chiral center in а molecule, and (2) the presence of “structural rigidity” in а molecule. Structural rigidity is caused by restricted rotation about chemical bonds. It is the basis for cis – trans stereoisomerism, а phenomenon found in some substituted cycloalkanes and some alkenes.
Stereoisomers can be subdivided into two types: enantiomers and diastereomers. Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of each other. Left- and right-handed forms of а molecule with а single chiral center are enantiomers.
Diastereomers are stereoisomers whose molecules are not mirror images of each other. Cis – trans isomers (of both the alkene and the cycloalkane types) are diastereomers. We will see additional examples of carbohydrate diastereomers in the next section. Stereoisomers that are not enantiomers are diastereomers; they must be one or the other.
Enantiomers Diastereomers
Fischer Projections. Drawing three-dimensional representations of chiral molecules, can be both time-consuming and awkward. Fischer projections represent а method for giving molecular chirality specifications in two dimensions. А Fischer projection is а two-dimensional notation showing the spatial arrangement of groups about chiral centers in molecules.
In а Fischer projection, а chiral center is represented as the intersection of vertical and horizontal lines. The atom at the chiral center, which is almost always carbon, is not explicitly shown.
The tetrahedral arrangement of the four groups attached to the atom at the chiral center is governed by the following conventions: (1) Vertical lines from the chiral center represent bonds to groups directed into the printed page. (2) Horizontal lines from the chiral center represent bonds to groups directed out of the printed page.
Fischer
projection
Our immediate concern is Fischer projections for monosaccharides. Such projections have the monosaccharide carbon chain positioned vertically with the carbonyl group (aldehyde or ketone) at or near the top.
The smallest monosaccharide that has а chiral center is the compound glyceraldehydes (2,3-dihydroxypropanal). The structural formula and Fischer projections for the two enantiomers of glyceraldehyde are
D-glyceraldehyde L-glyceraldehyde
The handedness (right and left) of these two enantiomers is specified by using the designations D and L. The enantiomer with the chiral center – ОН group on the right in the Fischer projection is by definition the right-handed isomer (в-glyceraldehyde), and the enantiomer with the chiral center – ОН group on the left in the Fischer projection is by definition the left-handed isomer (L-glyceraldehyde).
We now consider Fischer projections for the compound 2,3,4-trihydroxybutanal, а monosaccharide with four carbons and two chiral centers.
There are four stereoisomers for this compound – two pairs of enantiomers.
A B C D
First enantiomeric pair Second enantiomeric pair
In the first enantiomeric pair, both chiral center – ОН groups are on the same side of the Fischer projection, and in the second enantiomeric pair, the chiral center – ОН groups are on opposite sides of the Fischer projection. These are the only – ОН group arrangements possible.
The D, L system used to designate the handedness of glyceraldehyde enantiomers is extended to monosaccharides with more than one chiral center in the following manner.
The carbon chain is numbered, starting at the carbonyl group end of the molecule, and the highest-numbered chiral center is used to determine D or L configuration.
A B C D
D- isomer L-isomer D-isomer L- isomer
The D, L nomenclature gives the configuration (handedness) only at the highest-numbered chiral center. The configuration at other chiral centers in а molecule is accounted for by assigning а different commoame to each pair of D, L enantiomers. In our present example, compounds А and В (the first enantiomeric pair) are D-erythrose and L-erythrose; compounds С and D (the second enantiomeric pair) are D-threose and L-threose.
А and С are diastereomers, stereoisomers that are not mirror images of each other. Other diastereomeric pairs in our example are А and D, В and С, and В and D. These four pairs are epimers. Epimers are diastereomers that differ only in the configuration at one chiral center.
In general, а compound that haschiral centers may exist in а maximum of 2n stereoisomeric forms. For example, when three chiral centers are present, at most eight stereoisomers (23 = 8) are possible (four pairs of enantiomers).
Stereoisomers. 1. Isomers in which the atoms have the same connectivity but differ in spatial arrangement.
2. Stereoisomerism results either from the presence of а chrial center or from structural rigidity caused by restricted rotation about chemical bonds.
Enantiomers. 1. Stereoisomers that are nonsuperimposable mirror images of each other.
2.Handedness (D and L configuration) is determined by the configuration at the highest-numbered chiral center.
3. Enantiomers rotate plane-polarized light in different directions. (+) Enantiomers are dextrorotatory (clockwise), and (-) enantiomers are levorotatory (counterclockwise).
Diastereomers. 1. Stereoisomers that are not mirror images of each other.
2. Epimers are diastereomers whose configurations differ only at one chiral center.
Properties of Enantiomers. Structural isomers differ in most chemical and physical properties. For example, structural isomers have different boiling points and melting points. Diastereomers also differ in most chemical and physical properties. They also have different boiling points and freezing points. In contrast, nearly all the properties of а pair of enantiomers are the same; for example, they have identical boiling points and freezing points. Enantiomers exhibit property differences in only two areas: their interaction with plane-polarized light and their interaction with other chiral substances.
Interactions between chiral compounds. А left-handed baseball player (chiral) and а right-handed baseball player (chiral) can use the same baseball bat (achiral) or wear the same baseball hat (achiral). However, left- and right-handed baseball players (chiral) cannot use the same baseball glove (chiral). This nonchemical example illustrates that the chirality of an object becomes important when the object interacts with another chiral object.
Applying this generalization to molecules, we find that the two members of an enantiomeric pair, because of their differing chirality, interact differently with other chiral molecules. We find that:
1. А pair of enantiomers have the same solubility in an achiral solvent, such as ethanol, but differing solubilities in а chiral solvent, such as в-2-butanol.
2. The rate and extent of reaction of enantiomers with another reactant are the same if the reactant is achiral but differ if the reactant is chiral. The different reactions that different enantiomers undergo are further considered in the paragraph that follows.
3. Enantiomers have identical boiling points, freezing points, and densities, because such properties depend on the strength of intermolecular forces, and intermolecular force strength does not depend on chirality. Intermolecular force strength is the same for both forms of а chiral molecule, because both forms have identical sets of functional groups.
The two enantiomeric forms of а chiral molecule often generate different responses from the human body. Sometimes both enantiomers are biologically active, each form giving a different response; sometimes both give the same response, but one isomer’s response is many times greater than that of the other; and sometimes only one of the two forms is biologically active, the other form giving no response. For example, the body’s response to the D isomer of the hormone epinephrine is 20 times greater than its response to the L isomer. Epinephrine exerts its effect by binding to specialized receptors. It binds to the receptor site by means of а three-point contact, D-epinephrine makes а perfect three-point contact with the receptor surface, but the biologically weaker L-epinephrine can make only а two-point contact. Because of the poorer fit, the binding of the isomer is weaker, and less physiological response is observed.
Classification of Monosaccharides. Now that we have considered molecular chirality and its consequences, we return to the subject of carbohydrates by considering further details about monosaccharides, the simplest carbohydrates.
Although there is no limit to the number of carbon atoms that can be present in а monosaccharide, only monosaccharides with three to seven carbon atoms are commonly found iature. А three-carbon monosaccharide is called а triose, and those that contain four, five, and six carbon atoms are called tetroses, pentoses, and hexoses, respectively.
Monosaccharides are classified as aldoses or ketoses on the basis of type of carbonyl group present. Aldoses are monosaccharides that contain an aldehyde group. Ketoses are monosaccharides that contain а ketone group.
Monosaccharides are often classified by both their number of carbon atoms and their functional group. А six-carbon monosaccharide with an aldehyde functional group is an aldohexose; а five-carbon monosaccharide with а ketone functional group is а ketopentose.
Monosaccharides are also often called sugars. Hexoses are six-carbon sugars, pentoses five-carbon sugars, and so on. The word sugar is associated with “sweetness,” and most (but not all) monosaccharides have а sweet taste. The designation sugar is also applied to disaccharides, many of which also have а sweet taste. Thus sugar is а general designation for either а monosaccharide or а disaccharide.
The simplest aldose and ketose are the trioses glyceraldehyde and dihydroxyacetone.
glyceraldehydes dihydroxycaetone
The D and L designations specify the configuration at the highest-numbered chiral center in а monosaccharide. The configurations about other chiral centers are accounted for by assigning а different commoame to each pair of D and L enantiomers. This naming system, for simple aldoses, is given
The L forms are mirror images of the molecules shown.
А major difference between glyceraldehyde and dihydroxyacetone is that the latter does not possess а chiral carbon atom. Thus, D and L forms are not possible for dihydroxy acetone. This reduces by half (compared with aldoses) the number of stereoisomers possible for ketotetroses, ketopentoses, and ketohexoses. An aldohexose has four chiral carbon atoms, but а ketohexose has only three. atoins.
Cyclic forms of monosaccharides. So far in this chapter, the structures of monosaccharides have been depicted as open-chain polyhydroxy aldehydes or ketones. However, experimental evidence indicates that for monosaccharides containing five or more carbon atoms, such open-chain structures are actually in equilibrium with two cyclic structures, and the cyclic structures are the dominant forms at equilibrium.
The cyclic forms of monosaccharides result from the ability of their carbonyl group to react intramolecularly with а hydroxyl group. The result is а cyclic hemiacetal or cyclic hemiketal. Such an intramolecular cyclization reaction for D-glucose is shown:
Structure 2 is а rearrangement of the projection formula for D-glucose in which the carbon atoms have locations similar to those found for carbon atoms in а six-membered ring. All hydroxyl groups drawn to the right in the original projection formula appear below the ring. Those to the left in the projection formula appear above the ring.
Structure 3 is obtained by rotating the groups attached to carbon-5 in а counterclockwise direction so that they are in the positions where it is easiest to visualize intramolecular hemiacetal formation. The intramolecular reaction occurs between the hydroxyl group on carbon-5 and the carbonyl group (carbon-1). The – ОН group adds across the carbon – oxygen double bond, producing а heterocyclic ring that contains five carbon atoms and one oxygen atom.
Addition across the carbon – oxygen double bond with its accompanying ring formation produces а chiral center at carbon-l, so two stereoisomers are possible. These two forms differ in the orientation of the – ОН group on the hemiacetal carbon atom (carbon-1). In a-D-glucose, the – ОН group is on the opposite side of the ring from the CH2OH group attached to carbon-5. In b-D-glucose, the СН2ОН group on carbon-5 and the – ОН group on carbon-1 are on the same side of the ring.
In an aqueous solution of в-glucose, а dynamic equilibrium exists among the a, b, and open-chain forms, and there is continual interconversion among them. For example, a freshly mixed solution of pure a-D-glucose slowly converts to а mixture of both a– and b-D-glucose by an opening and а closing of the cyclic structure. When equilibrium is established, 63 % of the molecules are b-D-glucose, 37 % are a-D-glucose, and less than 0.01 % are in the open-chain form.
Intramolecular cyclic hemiacetal formation and the equilibrium between forms associated with it is not restricted to glucose. All aldoses with five or more carbon atoms establish similar equilibria, but with different percentages of the alpha, beta, and open-chain forms. Fructose and other ketoses with а sufficient number of carbon atoms also cyclize; here, cyclic hemiketal formation occurs.
Galactose, like glucose, forms а six-membered ring, but both D-fructose and D-ribose form а five-membered ring.
D-fructose D-ribose
D-Fructose cyclization involves carbon-2 (the keto group) and carbon-5, which results in two CH2OH groups being outside the ring (carbons 1 and 6). D-Ribose cyclization involves carbon-1 (the aldehyde group) and carbon-4.
Haworth Projection Formulas. The structural representations of the cyclic forms of monosaccharides found in the previous section are examples of Haworthprojection formulas. А Haworth projection is а of а carbohydrate.
In а Haworth projection, the hemiacetal ring system is viewed “edge on” with the oxygen ring atom at the upper right (six-membered ring) or at the top (five-membered ring).
The D or L form of а monosaccharide is determined by the position of the terminal СН2ОН group on the highest-numbered ring carbon atom. In the в form, this group is positioned above the ring. In the ь form, which is not usually encountered in biological systems, the terminal CH2OH group is positioned below the ring.
a or b configuration is determined by the position of the -ОН group on carbon-1 relative to the CH2OH group that determines D or L series. In а b configuration, both of these groups point in the same direction; in an a configuration, the two groups point in opposite directions.
b-D-Monosaccharide a-D-Monosaccharide b-L-Monosaccharide
Where a or b configuration does not matter, the -ОН group on carbon-1 is placed in a horizontal position, and а wavy line is used as the bond that connects it to the ring.
The specific identity of а monosaccharide is determined by the positioning of the other: – ОН groups in the Haworth projection. Any – ОН group at а chiral center that is to the right in а Fischer projection formula points down in the Haworth projection. Any group to the left in а Fischer projection points up in the Haworthprojection. The following is a matchup between Haworth projection and Fischer projection.
b-form a-form
Reactions of monosaccharides. Five important reactions of monosaccharides are oxidation, reduction, glycoside formation, phosphate ester formation, and amino sugar formation. In considering these reactions, we will use glucose as the monosaccharide reactant. Remember, however, that other aldoses as well as ketoses undergo similar reactions.
Oxidation. Monosaccharide oxidation can yield three different types of oxidation products. The oxidizing agent used determines the product.
Weak oxidizing agents, such as Tollens, Fehling’s, and Benedict’s solutions, oxidize the carbonyl group end of а monosaccharide to give an –onic acid. Oxidation of the aldehyde end of glucose produces gluconic acid, and oxidation of the aldehyde end of galactose produces galactonic acid. The structures involved in the glucose reaction are
D-Glucose D-Gluconic acid
Because monosaccharides act as reducing agents in such reactions, they are called reducing sugars. With Tollens solution, glucose reduces Ag+ ion to Ag, and with Benedict’s and Fehling’s solutions, glucose reduces Cu2+ ion to Cu+ ion. А reducing sugar is a carbohydrate that gives a positive test with Tollens, Benedict’s and Fehling’s solutions. All monosaccharides are reducing sugars.
Tollens, Fehling’s, and Benedict’s solutions can be used to test for glucose in urine, а symptom of diabetes. For example, using Benedict’s solution, we observe that if no glucose is present in the urine (а normal condition), the Benedict’s solution remains blue.
The presence of glucose is indicated by the formation of а red precipitate. Testing for the presence of glucose in urine is such а common laboratory procedure that much effort has been put into the development of easy-to-use test methods.
Strong oxidizing agents can oxidize both ends of а monosaccharide at the same time (the carbonyl group and the terminal primary alcohol group) to produce а dicarboxylic acid. Such polyhydroxy dicarboxylic acids are known as -aric acids. For glucose, such an oxidation produces glucaric acid.
Although it is difficult to do in the laboratory, in biological systems enzymes can oxidize the primary alcohol end of an aldose such as glucose, without oxidation of the aldehyde group, to produce а –uronic acid. For glucose, such an oxidation produces D-glucuronic acid.
Reduction. The carbonyl group present in а monosaccharide (either an aldose or а ketose) can be reduced to а hydroxyl group, using hydrogen as the reducing agent. For aldoses and ketoses, the product of the reduction is the corresponding polyhydroxy alcohol, which is sometimes called а sugar alcohol. For example, the reduction D-glucose gives D-glucitol.
D-Glucitol is also known by the commoame D-sorbitol. Hexahydroxy alcohols such as D-sorbitol have properties similar to those of the trihydroxy alcohol glycerol. These alcohols are used as moisturizing agents in foods and cosmetics because of their affinity for water. D-Sorbitol is also used as а sweetening agent in chewing gum; bacteria that cause tooth decay cannot use polyalcohols as food sources, as they can glucose and many other monosaccharides.
Mutarotation. a– and b-forms of monosaccharides are readily interconverted when dissolved in water. This spontaneous process, called mutarotation, results in an equilibrium mixture of a– and b-furanose forms and a– and b-pyranose forms. The open chain that is formed during muterotation can participate in oxidation-reduction reactions.
Glycoside Formation. As you known, that hemiacetals and hemiketals can react with alcohols in acid solution to produce acetals and ketals. Because the cyclic forms of monosaccharides are hemiacetals and hemiketals, they react with alcohols to form acetals and ketals, as is illustrated for the reaction of b-D-glucose with methyl alcohol.
b-D-glucose Methyl b-D-glucoside
The general name for monosaccharide acetals and ketals is glycoside. А glycoside is an acetal or а ketal forpined pот а cyclic monosaccharide. More specifically, а glycoside produced from glucose is а glucoside, from galactose а galactoside, and so on. Glycosides, like the hemiacetals and hemiketals from which they are formed, can exist in both a and b forms. Glycosides are named by listing the alkyl or aryl group attached to the oxygen, followed by the name of the monosaccharide involved, with the suffix –ide appended to it.
Phosphate ester formation. The hydroxyl groups of а monosaccharide can react with inorganic oxyacids to form inorganic esters. Phosphate esters, formed from phosphoric acid and various monosaccharides, are commonly encountered in biological systems. For example, specific enzymes in the human body catalyze the esterification of the carbonyl group (carbon-1) and the primary alcohol group (carbon-6) in glucose to produce the compounds glucose 1-phosphate and glucose б-phosphate, respectively.
a-D-Glucose-1-phosphate a-D-Glucose-6-phosphate
These phosphate esters of glucose are stable in aqueous solution and play important roles in the metabolism of carbohydrates.
Amino Sugar Formation. Amino sugars of glucose, mannose, and galactose are common iature. Such sugars are produced by replacing the hydroxyl group on carbon-2 on the monosaccharide with an amino group. Amino sugars and their N-acetyl derivatives are important building blocks of polysaccharides found in cartilage.
a–D–Glucosamine a–D–Glalactosamine N–acety1a–D–glucosanune
The N-acetyl derivatives of D-glucosamine and D-galactosamine are present in the biochemical markers on red blood cells, which distinguish the various blood types.
Isomerization. Monosaccharides undergo several types of isomerization, for example, after several hours an alkaline solution of D-glucose will also contain D- mannose and D- fructose. Both isomerizations involve an intramolecular shift of a hydrogen atom and a charge in the location of a double bond.
The intermediate that is formed during this process is called an enediol. The reversible transformation of glucose to fructose is an example of an aldose-ketose interconversion. Because there is a change in the conversion of glucose to mannose is referred to as an epimerization. Several enzyme-catalyzed reactions involving enediols occur in carbohydrate metabolism.
