Carbohydrates: Monosaccharides

            Carbohydrates are major functional constituents of living systems. The primary source of energy in animal cells, carbohydrates are synthesized in green plants from carbon dioxide, water, and solar energy. They give the skeletal system to tissues and organs of the human body and serve as lubricants and support elements of connective tissue. Major energy needs of the human body are met by dietary carbohydrates. They confer biological specificity and supply recognition elements on cell membranes. In addition, they are components of nucleic acids and are covalently linked with lipids and proteins.

Classification:

            Carbohydrates consist of polyhydroxyketone or polyhydroxyaldehyde compounds and their on densation products. The term "carbohydrate" means hydrate of carbon, a compound with an empirical formula (CH2O)n. This formula applies to many carbohydrates, such as glucose, which is C6H12O6, or (CH2O)6. However, a large number of compounds are classified as carbohydrates even though they do not have this empirical formula; these compounds are derivatives of simple sugars (e.g., C5H10O4). 

            Carbohydrates might be classified as monosaccharides, oligosaccharides, and polysaccharides; the term saccharide is derived from the Greek word for sugar. Monosaccharides are single polyhydroxyaldehyde or polyhydroxyketone units (e.g., fructose), whereas oligosaccharides consist of two to ten monosaccharide units joined together by glycosidic linkages. Sucrose and lactose are disaccharides, since they are each made up of two monosaccharide units. Polysaccharides, also called as glycans, are polymers that might contain many hundreds of monosaccharide units. They are further divided into homopolysaccharides and heteropolysaccharides. The former contain only a single type of polysaccharide unit (e.g., starch and cellulose, both of which are polymers of glucose), whereas the latter contain two or more different monosaccharide units.

Monosaccharides:

• Monosaccharides are recognized by their carbonyl functional group (aldehyde or ketone) and by the number of carbon atoms they contain. 
• The simplest monosaccharides are the two trioses, 3 carbon sugar: glyceraldehyde (an aldotriose); and dihydroxyacetone (a ketotriose). 
• Four, five, six, and seven-carbon-containing monosaccharides are called tetroses, pentoses, hexoses, and heptoses, respectively. 
• All monosaccharides, with the exception of dihydroxyacetone, contain at least one asymmetrical or chiral carbon atom, and therefore two or more stereoisomers are possible for each monosaccharide depending on the number of asymmetrical centers it contains. 
• Glyceraldehyde, with one asymmetrical center, has two possible stereoisomers, designated D and L forms. A method for representing the O and L forms is the Fischer projection formula. The D and L forms are used for all monosaccharides. 
• The designation of D or L, given to a monosaccharide with two or more asymmetrical centers, is based on the configuration of the asymmetrical carbon atom located farthest from the carbonyl functional group. 
• Thus, if the configuration at that carbon is the same as that of D-glyceraldehyde (with the hydroxyl group on the right-hand side), it belongs to the D series. 
• A similar relationship exists between L-glyceraldehyde (with the hydroxyl group on the left-hand side) and the L series of monosaccharides. 
• The optical rotation of a monosaccharide with numerous asymmetrical centers is the net result of contributions from the rotations of each optically active center. 
• Thus, the prefix D or L do not provide information with regard to optical rotation; it indicates only the configuration around the asymmetrical carbon atom located farthest from the carbonyl carbon. 
• The numbering system for monosaccharides depends on the location of the carbonyl carbon (or potential carbonyl carbon), which is assigned the lowest possible number. 
• For glucose (an aldohexose), carbon C1 bears the carbonyl group and the farthest asymmetrical carbon atom is C5 (the penultimate carbon), the configuration around which determines the O and L series. For fructose (a ketohexose), C2, bears the carbonyl group and C5 is the highest numbered asymmetrical carbon atom. 
• Glucose and fructose have identical configurations around C3 to C6. The structure of glucose, written in straight-chain form, shows four asymmetrical centers. 
• In general, the total number of possible isomers with a compound of n asymmetrical centers is 2". Thus, for aldohexoses having four asymmetrical centers, 16 isomers are possible, 8 of which are mirror images of the other 8 (enantiomers). 
• These two groups contains members of the D and L series of aldohexoses. Most of the physiologically important isomers belong to the D series, although a few L-isomers are also found. The designation of D and L is omitted, and it is assumed that a monosaccharide belongs to the D series unless it is specifically designated an L-isomer. 
• Of the D-series of aldohexoses, three are physiologically important: D-glucose, D-galactose, and D-mannose. Structurally, D-glucose and D-galactose differ only in the configuration around C4; D-glucose and D-mannose differ only in the configuration around C2. 
• Pairs of sugars (e.g., glucose and galactose, glucose and mannose), which differ only in the configuration around a single carbon, are known as epimers. 
• D-Galactose and D-mannose are not epimers, since they differ in configurations around both C2 and C4. 
• D-Fructose, one of eight 2-ketohexoses, is the physiologically important ketohexose.
• Monosaccharides with five or more carbons occur mostly in cyclic forms owing to a reaction between the carbonyl group (aldehyde or ketone) and an alcohol group. 
• Formation of the cyclic forms of monosaccharides is favored because these structures have lower energies than the straight-chain forms. 
• Cyclic forms of D-glucose are formed by the hemiacetal linkage between the C1 aldehyde group and the C4 or C5 alcohol group. If the ring structure is formed between C1 and C4, the resulting five-membered ring structure is named D-glucofuranose because it resembles the compound furan. If the ring structure is formed between C1 and C5, the resulting six-membered ring is named D-glucopyranose because it resembles the compound pyran.
• Aldohexoses exist in solutions mainly in six-membered pyranose ring forms, since these forms are thermodynamically more stable than furanose ring forms. 
• Cyclization of a monosaccharide leads in the occurance of an additional asymmetrical center, known as the anomeric carbon, when the carbon of the carbonyl  group reacts with the C5 hydroxyl group. The two possible stereoisomers resulting from the cyclization are called α- and β-anomers. 
• Aldohexoses in their cyclic forms contain five asymmetrical centers and therefore 32 stereoisomers. It can be explained, each of the 16 isomers that belong to the D or L series has two anomeric forms. 
• The systematic names for these two anomers are α-D-glucopyranose and β-D-glucopyranose. Three-dimensional representations of ring structures are frequently shown as Haworth projection formulas, in which the lower edge of the ring is presented as a thick line, to indicate that this part of the structure projects out toward the observer, and the upper edge as a thin line that projects behind the plane of the paper. 
• Carbon atoms of the ring are not clearly shown but occur at junctions of lines representing bonds. Sometimes the hydrogen atoms are also omitted and are presumed to exist wherever a bond line ends without a specified group. 
• The pyranose ring is not planar, being similar to structure of cyclohexane. The bond angles in cyclohexane are similar to those between the bonds of a tetrahedral carbon (i.e.,109 degrees).  
• In the pyranose ring, all bond angles are similar to those of cyclohexane, including the hemiacetal C-O-C bond angle, which is 111 degrees.  
• Most pyranoses occur in the chair conformation, in which most of the substituents can assume equatorial positions (i.e., lie approximately in the same plane as the ring) instead of axial positions (i.e., lie approximately vertically above or below the plane of the ring). 
• In the equatorial positions, the bulky substituent groups (-OH,-CH2OH) can more easily be accommodated than in the axial positions, and the preferred conformation is usually the chair conformation. 
• However, two chair forms can be drawn for each of the two anomers of D-glucopyranose for β-D-glucopyranose. The structure on top is designated the 4C1 form because it contains carbon 4 and carbon 1 above and below the plane of the molecule, respectively. 
• The designation of 1C4 for the structure on the bottom conveys the opposite sense. In the 4C1 conformation, all the large substituent groups are in equatorial positions, whereas in the 1C4 conformation, they are in axial positions. 4C1 is the more stable and therefore the preferred chair conformation.
• In aqueous solutions, the β-anomer of glucose is better solvated, more stable, and therefore the predominant form. However, for other aldohexoses (e.g., mannose and galactose), the α-anomer is more stable than the β-anomer because of the dipole effect. 
• The dipole effect involves the C 1-hydroxyl group and the ring oxygen. In the α-anomer, the dipoles of the axial C 1-hydroxyl group and the ring oxygen are nearly antiparallel, whereas in the β -anomer, the dipoles of the equatorial C 1-hydroxyl group and the ring oxygen are nearly parallel. 
• The dipoles impart stability to a structure when they are antiparallel. Although the dipole effect is also applicable to α- and β-anomers of glucose, the solvation effect overrides the dipole effect. 
• Inter conversion of α- and β-forms can be followed in a polarimeter by measuring the optical rotation. Crystallization of D-glucose from water yields α -D-glucopyranose, a form which is least soluble and has a specific rotation of +112.2 degrees. 
• Ordinary crystalline glucose is in the α-form, but if the crystallization of D-glucose takes place in pyridine, β-D-glucopyranose, which has a specific rotation of + 18.7 degrees is obtained. Freshly prepared solutions of the α- and β-forms show specific rotations of .1.112.2 degrees and +18.7 degrees respectively. 
• However, over a period of a few hours at room temperature, the specific rotation of both forms in aqueous solution changes and attains a stable value of .1.52.7 degrees. This change in optical rotation, mutarotation, is characteristic of sugars that form cyclic structures.
• D-Fructose, a ketohexose, can potentially form either a five-membered (furanose) or a six-membered (pyranose) ring involving formation of an internal hemiketal linkage between C2 (the anomeric carbon atom) and the C5 or C6 hydroxyl group, respectively. 
• The hemiketal linkage introduces a new asymmetrical center at the C2 position. Thus, two anomeric forms of each of the fructofuranose and fructopyranose ring structures are possible. In aqueous solution at equilibrium, fructose is present predominantly in the β -fructopyranose form. 
• Fructose 1,6-bisphosphate is present in the β-fructofuranose form, with a 4:1 ratio of β- to α –anomeric forms. Fructose is a major constituent (38%) of honey; the other constituents are glucose (31%), water (17%), maltose (a glucose disaccharide, 7%), sucrose (a glucose-fructose disaccharide, 1%), and polysaccharide (1%). The difference of these sugars in honey from different sources is quite large.

Sugar Alcohols:

• Sugar alcohols are polyhydric alcohols formed when the carbonyl group of the sugar (monosaccharide) is reduced to a hydroxyl group. 
• For example, reduction of glyceraldehyde or dihydroxyacetone yields glycerol, a component of triacylglycerols and of phospholipids. D-Sorbitol is formed when D-glucose is reduced. 
• Keto sugars of more than three carbons can give more than one sugar alcohol. Sorbitol, which has about 35-60% of the sweetness of sucrose, is used as a sweetener and flavoring agent. 
• It absorbs moisture from the air and therefore is used as a humectant. Sorbitol can gather in tissues such as the lens, sciatic nerve, and renal papillae in certain disorders like diabetes mellitus and galactosemia and can lead to pathological changes. 
• In these cases, the intracellular accumulation of sugar alcohols is due to the high levels of precursor sugars in the plasma, which are converted enzymatically to the sugar alcohols in the cytoplasm. 
• Sugar alcohols are not degraded or synthesized as rapidly as their precursors, and reconversion to the precursor is also slow. 
• Mannitol is widely occured in nature and occurs in the exudates of many plants. It possess about half the sweetness of sucrose. 
• Clinically, mannitol is administered intravenously to the patients with renal failure as an osmotic diuretic. It is not metabolized properly, is filtered by the glomerulus, and is not reabsorbed by the tubules; hence, it is excreted in urine. 
• The non reabsorbable solute holds water, limits back-diffusion, and thus maintains urine volume in the presence of decreased glomerular activity. 
• Intravenous mannitol is also used to reduce an increase in pressure and in volume of cerebrospinal fluid. Xylitol, a five-carbon compound, is widely distributed in the plant kingdom. 
• Xylitol has more than twice the sweetness of sucrose. A potential benefit of xylitol and other sugar alcohols used as sucrose substitutes might be the prevention of dental caries. The beneficial effect might be due to the inability of the oral microorganisms to utilize the sugar alcohols. 
• Sugar alcohols, though formed from reducing monosaccharides, are not reducing agents and exist only in the straight-chain form, since they cannot form cyclic hemiacetal or hemiketal linkages. However, cyclic compounds related to sugar alcohols do exist like myo-inositol, a component of some phospholipids.

Sugar Acids:

• The sugar acids are formed when a carbonyl group or a -OH group is oxidized to a carboxylic acid group. The biologically important sugar acids are aldonic and uronic acids. 
• An aldonic acid is obtained when the aldehyde group in an aldo sugar is oxidized; thus, oxidation of D-glucose at C1 gives D-gluconic acid. Aldonic acids cannot stay in hemiacetal ring structures but can form cyclic structures via an ester linkage between the carboxylic group and one of the hydroxyl groups of the same molecule. 
• This kind of cyclic ester is known as a lactone. Uronic acids, in which the highest numbered carbon atom possesses the carboxyl group, can form cyclic hemiacetal ring structures because they possess an accessible carbonyl group. 
• They can form glycosidic bonds with other uronic acids or monosaccharides to give polysaccharides. At physiological pH, uronic acids occur in the ionized form. Vitamin C is derivative of D-glucronate.

Amino Sugar:

• Amino sugars are formed by replacing a -OH group of a monosaccharide by an amino group. The most common amino sugars are the 2-aminoaldohexoses, namely, D-glucosamine and D-galactosamine. 
• The amino groups usually present as the N-acetyl derivatives. Amino sugars are components of structural polysaccharides and of membrane's glycosphingolipids. 
• N-Acetylmuramic acid is  a part of a bacterial cell wall polysaccharide and has a lactyl side chain linked to C3 of glucosamine via an ether linkage. 
• The polysaccharide is a polymer of alternating N-acetylmuramic acid and N-acetylglucosamine residues linked in a β (1-->4) glycosidic bond. 
• Lysozyme catalyzes the cleavage of these bonds. The polysaccharide chains are cross-linked through short peptides and the entire structure is called as a peptidoglycan. 
• N-Acetylneuraminic acid, known as sialic acid, is a derivative of a ketonanose. It occurs in the oligosaccharide side chains of some glycoproteins and in gangliosides, both of which are parts of cell membranes.

Sugar Phosphates:

• Sugar phosphates are phosphoric acid esters of monosaccharides, obtain as intermediates in carbohydrate metabolism. 
• Two of these compounds, ribose phosphate and deoxyribose phosphate, are constituents of nucleic acids (DNA and RNA) and it's monomers (nucleotides).
• Glucose can be phosphorylated either at the C6 primary hydroxyl group to yield glucose 6-phosphate or at the C1 anomeric hydroxyl group to yield glucose 1-phosphate. In glucose 1-phosphate, the phosphate group can occur in either the α- or β-position. 
• These two forms are not interconverted in solution because the substitution of the anomeric hydroxyl group by any other group prevents the ring opening which is key factor for the equilibration of anomers. 
• The reducing property is also lost. Another kind of sugar phosphates consists of nucleoside diphosphate sugars, in which a monosaccharide is attached via anomeric -OH group to a nucleoside diphosphate. 
• A nucleoside contains D-ribose, an aldopentose, attached to a purine or a pyrimidine base, as in uridine diphosphate glucose. Such compounds are essential in the synthesis of polysaccharides, the interconversion of sugars, and the synthesis of glycosides.

Deoxy Sugars:

• In deoxy sugars, one or more -OH groups of the pyranose or furanose ring is substituted by hydrogen atom 
• A well-known example is 2-deoxyribose, which is a component of deoxyribonucleotides, the monomeric units of deoxyribonucleic acids. 
• Another example is L-fucose (6-deoxyl-L-galactose), a constituent of cell membrane glycoproteins and glycolipids and one ofthe few monosaccharides that exist in the L-configuration. 
• L-Fucose exists either at terminal or preterminal positions of numerous cell surface oligosaccharide ligands. These fucosylated oligosaccharides help in cell-cell recognition and adhesion-signaling pathways. 
• The cell-cell adhesion guided by fucosylated oligosaccharide involves cell surface Ca-dependent binding proteins known as selectins.

Glycosides:

• Glycosides are obtained when the anomeric hydroxyl group of a monosaccharide undergoes condensation with the hydroxyl group of a second molecule, with the removal of water. 
• Formation of glycosides is an example of acetal formation, which is a result of reaction between a hemiacetal group and another -OH group. 
• The linkage occuring from such a reaction is known as a glycosidic bond. 
• If glucose provides the hemiacetal group, the obtained molecule is a glucoside; if galactose provides the hemiacetal group, the molecule obtained is a galactoside.  
• When glucose reacts with methanol at an increased temperature in the presence of an acid catalyst, a mixture of α- and β-methyl glucopyranosides is formeed. 
• Once the anomeric hydroxyl group is replaced, properties associated with the anomeric carbon atom, such as, mutarotation, reduction, and ring size are permanently lost. 
• The noncarbohydrate moiety of a glycoside is known as the aglycone. Methanol, glycerol, phenols, and sterols might act as aglycones. 
• Adenosine, a major constituent of nucleotides and genetic material, is an N-glycoside.