The Structure of Glucose Can Be Represented in Three Ways
The straight-chain structural formula (aldohexose; Figure 15–1A) can account for some of the properties of glucose, but a cyclic structure (a hemiacetal formed by reaction between the aldehyde group and a hydroxyl group) is thermodynamically favored and accounts for other properties. The cyclic structure is normally drawn as shown in Figure 15–1B, the Haworth projection, in which the molecule is viewed from the side and above the plane of the ring; the bonds nearest to the viewer are bold and thickened, and the hydroxyl groups are above or below the plane of the ring. The hydrogen atoms attached to each carbon are not shown in this figure. The ring is actually in the form of a chair (Figure 15–1C).
d-Glucose. (A) Straight-chain form. (B) α-d-glucose; Haworth projection. (C) α-d-glucose; chair form.
Sugars Exhibit Various Forms of Isomerism
Glucose, with four asymmetric carbon atoms, can form 16 isomers. The more important types of isomerism found with glucose are as follows.
d and l isomerism: The designation of a sugar isomer as the d form or its mirror image as the l form is determined by its spatial relationship to the parent compound of the carbohydrates, the three-carbon sugar glycerose (glyceraldehyde). The l and d forms of this sugar, and of glucose, are shown in Figure 15–2. The orientation of the —H and —OH groups around the carbon atom adjacent to the terminal alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to the d or l series. When the —OH group on this carbon is on the right (as seen in Figure 15–2), the sugar is the d isomer; when it is on the left, it is the l isomer. Most of the naturally occurring monosaccharides are d sugars, and the enzymes responsible for their metabolism are specific for this configuration.
The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a solution of an optical isomer, it rotates either to the right, dextrorotatory (+), or to the left, levorotatory (−). The direction of rotation of polarized light is independent of the stereochemistry of the sugar, so it may be designated d(−), d(+), l(−), or l(+). For example, the naturally occurring form of fructose is the d(−) isomer. Confusingly, dextrorotatory (+) was at one time called d-, and levorotatory (−) l-. This nomenclature is obsolete, but may sometimes be found; it is unrelated to d- and l-isomerism. In solution, glucose is dextrorotatory, and glucose solutions are sometimes known as dextrose.
Pyranose and furanose ring structures: The ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring) (Figures 15–3 and 15–4). For glucose in solution, more than 99% is in the pyranose form.
Alpha and beta anomers: The ring structure of an aldose is a hemiacetal, since it is formed by reaction between an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal. Crystalline glucose is α-d-glucopyranose. The cyclic structure is retained in the solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of α-glucopyranose (38%) and β-glucopyranose (62%). Less than 0.3% is represented by α and β anomers of glucofuranose.
Epimers: Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose (epimerized at carbon 2) and galactose (epimerized at carbon 4) (Figure 15–5).
Aldose-ketose isomerism: Fructose has the same molecular formula as glucose but differs in that there is a potential keto group in position 2, the anomeric carbon of fructose, whereas in glucose there is a potential aldehyde group in position 1, the anomeric carbon. Examples of aldose and ketose sugars are shown in Figures 15–6 and 15–7. Chemically, aldoses are reducing compounds, and are sometimes known as reducing sugars. This provides the basis for a simple chemical test for glucose in urine in poorly controlled diabetes mellitus, by reduction of an alkaline copper solution (Chapter 48).
d- and l-isomerism of glycerose and glucose.
Pyranose and furanose forms of glucose.
Pyranose and furanose forms of fructose.
Examples of aldoses of physiological significance.
Examples of ketoses of physiological significance.
Many Monosaccharides Are Physiologically Important
Derivatives of trioses, tetroses, and pentoses and of the seven-carbon sugar sedoheptulose, are formed as metabolic intermediates in glycolysis (see Chapter 17) and the pentose phosphate pathway (see Chapter 20). Pentoses are important in nucleotides, nucleic acids, and several coenzymes (Table 15–2). Glucose, galactose, fructose, and mannose are physiologically the most important hexoses (Table 15–3). The biochemically important ketoses are shown in Figure 15–6, and aldoses in Figure 15–7.
TABLE 15–2Pentoses of Physiological Importance ||Download (.pdf) TABLE 15–2 Pentoses of Physiological Importance
|Sugar ||Source ||Biochemical and Clinical Importance |
|d-Ribose ||Nucleic acids and metabolic intermediate ||Structural component of nucleic acids and coenzymes, including ATP, NAD(P), and flavin coenzymes |
|d-Ribulose ||Metabolic intermediate ||Intermediate in the pentose phosphate pathway |
|d-Arabinose ||Plant gums ||Constituent of glycoproteins |
|d-Xylose ||Plant gums, proteoglycans, glycosaminoglycans ||Constituent of glycoproteins |
|l-Xylulose ||Metabolic intermediate ||Excreted in the urine in essential pentosuria |
TABLE 15–3Hexoses of Physiological Importance ||Download (.pdf) TABLE 15–3 Hexoses of Physiological Importance
|Sugar ||Source ||Biochemical Importance ||Clinical Significance |
|d-Glucose ||Fruit juices, hydrolysis of starch, cane or beet sugar, maltose and lactose ||The main metabolic fuel for tissues; “blood sugar” ||Excreted in the urine (glucosuria) in poorly controlled diabetes mellitus as a result of hyperglycemia |
|d-Fructose ||Fruit juices, honey, hydrolysis of cane or beet sugar and inulin, enzymic isomerization of glucose syrups for food manufacture ||Readily metabolized either via glucose or directly ||Hereditary fructose intolerance leads to fructose accumulation and hypoglycemia |
|d-Galactose ||Hydrolysis of lactose ||Readily metabolized to glucose; synthesized in the mammary gland for synthesis of lactose in milk. A constituent of glycolipids and glycoproteins ||Hereditary galactosemia as a result of failure to metabolize galactose leads to cataracts |
|d-Mannose ||Hydrolysis of plant mannan gums ||Constituent of glycoproteins || |
In addition, carboxylic acid derivatives of glucose are important, including d-glucuronate (for glucuronide formation and in glycosaminoglycans), its metabolic derivative, l-iduronate (in glycosaminoglycans, Figure 15–8) and l-gulonate (an intermediate in the uronic acid pathway; see Figure 20–4).
α-d-Glucuronate (left) and β-l-iduronate (right).
Sugars Form Glycosides With Other Compounds & With Each Other
Glycosides are formed by condensation between the hydroxyl group of the anomeric carbon of a monosaccharide, and a second compound that may be another monosaccharide or, in the case of an aglycone, not a sugar. If the second group is also a hydroxyl, the O-glycosidic bond is an acetal link because it results from a reaction between a hemiacetal group (formed from an aldehyde and an —OH group) and another —OH group. If the hemiacetal portion is glucose, the resulting compound is a glucoside; if galactose, a galactoside; and so on. If the second group is an amine, an N-glycosidic bond is formed, for example, between adenine and ribose in nucleotides such as ATP (see Figure 11–4).
Glycosides are widely distributed in nature; the aglycone may be methanol, glycerol, a sterol, a phenol, or a base such as adenine. The glycosides that are important in medicine because of their action on the heart (cardiac glycosides) all contain steroids as the aglycone. These include derivatives of digitalis and strophanthus such as ouabain, an inhibitor of the Na+–K+-ATPase of cell membranes. Other glycosides include antibiotics such as streptomycin.
Deoxy Sugars Lack an Oxygen Atom
Deoxy sugars are those in which one hydroxyl group has been replaced by hydrogen. An example is deoxyribose (Figure 15–9) in DNA. The deoxy sugar l-fucose (Figure 15–15) occurs in glycoproteins; 2-deoxyglucose is used experimentally as an inhibitor of glucose metabolism.
2-Deoxy-d-ribofuranose (β form).
Amino Sugars (Hexosamines) Are Components of Glycoproteins, Gangliosides, & Glycosaminoglycans
The amino sugars include d-glucosamine, a constituent of hyaluronic acid (Figure 15–10), d-galactosamine (also known as chondrosamine), a constituent of chondroitin, and d-mannosamine. Several antibiotics (eg, erythromycin) contain amino sugars, which are important for their antibiotic activity.
Glucosamine (2-amino-d-glucopyranose) (α form). Galactosamine is 2-amino-d-galactopyranose. Both glucosamine and galactosamine occur as N-acetyl derivatives in complex carbohydrates, for example, glycoproteins.
Maltose, Sucrose, & Lactose Are Important Disaccharides
The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond (Figure 15–11). The physiologically important disaccharides are maltose, sucrose, and lactose (Table 15–4). Hydrolysis of sucrose yields a mixture of glucose and fructose called "invert sugar" because fructose is strongly levorotatory and changes (inverts) the weaker dextrorotatory action of sucrose.
Structures of nutritionally important disaccharides.
TABLE 15–4Disaccharides of Physiological Importance ||Download (.pdf) TABLE 15–4 Disaccharides of Physiological Importance
|Sugar ||Composition ||Source ||Clinical Significance |
|Sucrose ||O-α-d-glucopyranosyl-(1→2)-β-d-fructofuranoside ||Cane and beet sugar, sorghum and some fruits and vegetables ||Rare genetic lack of sucrase leads to sucrose intolerance—diarrhea and flatulence |
|Lactose ||O-α-d-galactopyranosyl-(1→4)-β-d-glucopyranose ||Milk (and many pharmaceutical preparations as a filler) ||Lack of lactase (alactasia) leads to lactose intolerance—diarrhea and flatulence; may be excreted in the urine in pregnancy |
|Maltose ||O-α-d-glucopyranosyl-(1→4)-α-d-glucopyranose ||Enzymic hydrolysis of starch (amylase); germinating cereals and malt || |
|Isomaltose ||O-α-d-glucopyranosyl-(1→6)-α-d-glucopyranose ||Enzymic hydrolysis of starch (the branch points in amylopectin) || |
|Lactulose ||O-α-d-galactopyranosyl-(1→4)-β-d-fructofuranose ||Heated milk (small amounts), mainly synthetic ||Not hydrolyzed by intestinal enzymes, but fermented by intestinal bacteria; used as a mild osmotic laxative |
|Trehalose ||O-α-d-glucopyranosyl-(1→1)-α-d-glucopyranoside ||Yeasts and fungi; the main sugar of insect hemolymph || |