Chapter 7: Introduction to Carbohydrates

Intro

Contents

Overview

Carbohydrates are the most abundant organic molecules in nature. They have a wide range of functions, including providing a significant fraction of the dietary calories for most organisms, acting as a storage form of energy in the body, and serving as cell membrane components that mediate some forms of intercellular communication. Carbohydrates also serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. The empiric formula for many of the simpler carbohydrates is (CH2O)n, hence the name “hydrate of carbon.”

Classification and Structure of Carbohydrates

Monosaccharides (simple sugars) can be classified according to the number of carbon atoms they contain. Examples of some monosaccharides commonly found in humans are listed in Figure 7.1. Carbohydrates with an aldehyde as their most oxidized functional group are called aldoses, whereas those with a keto as their most oxidized functional group are called ketoses (Figure 7.2). For example, glyceraldehyde is an aldose, whereas dihydroxyacetone is a ketose.

Carbohydrates that have a free carbonyl group have the suffix –ose. [Note: Ketoses (with some exceptions, for example, fructose) have an additional two letters in their suffix: –ulose, for example, xylulose.] Monosaccharides can be linked by glycosidic bonds to create larger structures (Figure 7.3). Disaccharides contain two monosaccharide units, oligosaccharides contain from three to about ten monosaccharide units, whereas polysaccharides contain more than ten monosaccharide units, and can be hundreds of sugar units in length.

Figure 7.1.Examples of monosaccharides found in humans, classified according to the number of carbons they contain.

Examples of monosaccharides found in humans, classified according to the number of carbons they contain

Figure 7.2.Examples of an aldose (A) and a ketose (B) sugar.

Examples of an aldose (A) and a ketose (B) sugar

Figure 7.3.A glycosidic bond between two hexoses producing a disaccharide.

A glycosidic bond between two hexoses producing a disaccharide

A. Isomers and epimers

Compounds that have the same chemical formula but have different structures are called isomers. For example, fructose, glucose, mannose, and galactose are all isomers of each other, having the same chemical formula, C6H12O6. Carbohydrate isomers that differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon, see “anomers” below) are defined as epimers of each other.

For example, glucose and galactose are C-4 epimers—their structures differ only in the position of the –OH group at carbon 4. [Note: The carbons in sugars are numbered beginning at the end that contains the carbonyl carbon—that is, the aldehyde or keto group (Figure 7.4).] Glucose and mannose are C-2 epimers. However, galactose and mannose are NOT epimers—they differ in the position of –OH groups at two carbons (2 and 4) and are, therefore, defined only as isomers (see Figure 7.4).

Figure 7.4. C-2 and C-4 epimers and an isomer of glucose.

C-2 and C-4 epimers and an isomer of glucose

B. Enantiomers

A special type of isomerism is found in the pairs of structures that are mirror images of each other. These mirror images are called enantiomers, and the two members of the pair are designated as a d- and an l-sugar (Figure 7.5). The vast majority of the sugars in humans are d-sugars. In the d isomeric form, the –OH group on the asymmetric carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right, whereas in the l-isomer it is on the left. Enzymes known as racemases are able to interconvert d- and l-isomers.

Figure 7.5.Enantiomers (mirror images) of glucose.

Enantiomers (mirror images) of glucose

C. Cyclization of monosaccharides

Less than 1? of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form. Rather, they are predominantly found in a ring (cyclic) form, in which the aldehyde (or keto) group has reacted with an alcohol group on the same sugar, making the carbonyl carbon (carbon 1 for an aldose or carbon 2 for a ketose) asymmetric. [Note: Pyranose refers to a six-membered ring consisting of five carbons and one oxygen, for example, glucopyranose (Figure 7.6), whereas furanose denotes a five-membered ring with four carbons and one oxygen.]

Figure 7.6.

Figure 7.6

A The interconversion (mutarotation) of the ? and ? anomeric forms of glucose shown as modified Fischer projection formulas. B The interconversion shown as Haworth projection formulas. Carbon 1 is the anomeric carbon.[Note: Glucose is a reducing sugar.]

1. Anomeric carbon

Cyclization creates an anomeric carbon (the former carbonyl carbon), generating the ? and ? configurations of the sugar, for example, ?-d-glucopyranose and ?-d-glucopyranose (see Figure 7.6). These two sugars are both glucose but are anomers of each other. [Note: In the ? configuration, the OH on the anomeric C projects to the same side as the ring in a modified Fischer projection formula (Figure 7.6A), and is trans to the CH2OH group in a Haworth projection formula (Figure 7.6B).

Because the ? and ? forms are not mirror images, they are referred to as diastereomers.] Enzymes are able to distinguish between these two structures and use one or the other preferentially. For example, glycogen is synthesized from ?-d-glucopyranose, whereas cellulose is synthesized from ?-d-glucopyranose. The cyclic ? and ? anomers of a sugar in solution are in equilibrium with each other, and can be spontaneously interconverted (a process called mutarotation, see Figure 7.6).

2. Reducing sugars

If the hydroxyl group on the anomeric carbon of a cyclized sugar is not linked to another compound by a glycosidic bond, the ring can open. The sugar can act as a reducing agent, and is termed a reducing sugar. Such sugars can react with chromogenic agents (for example, Benedict’s reagent or Fehling’s solution) causing the reagent to be reduced and colored, with the aldehyde group of the acyclic sugar becoming oxidized. [Note: Only the state of the oxygen in the aldehyde group determines if the sugar is reducing or nonreducing.]

A colorimetric test can detect a reducing sugar in urine. A positive result is indicative of an underlying pathology because sugars are not normally present in urine, and can be followed up by more specific tests to identify the reducing sugar

D. Joining of monosaccharides

Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), and maltose (glucose + glucose). Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources); each is a polymer of glucose. The bonds that link sugars are called glycosidic bonds. These are formed by enzymes known as glycosyltransferases that use nucleotide sugars such as UDP-glucose as substrates.

1. Naming glycosidic bonds

Glycosidic bonds between sugars are named according to the numbers of the connected carbons, and with regard to the position of the anomeric hydroxyl group of the sugar involved in the bond. If this anomeric hydroxyl is in the ? configuration, the linkage is an ?-bond. If it is in the ? configuration, the linkage is a ?-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of ?-galactose and carbon 4 of glucose. The linkage is, therefore, a ?(1?4) glycosidic bond (see Figure 7.3). [Note: Because the anomeric end of the glucose residue is not involved in the glycosidic linkage it (and, therefore, lactose) remains a reducing sugar.]

E. Complex carbohydrates

Carbohydrates can be attached by glycosidic bonds to non-carbohydrate structures, including purine and pyrimidine bases (found in nucleic acids), aromatic rings (such as those found in steroids and bilirubin), proteins (found in glycoproteins and proteoglycans), and lipids (found in glycolipids).

1. N- and O-glycosides

If the group on the non-carbohydrate molecule to which the sugar is attached is an ?NH2 group, the structure is an N-glycoside and the bond is called an N-glycosidic link. If the group is an –OH, the structure is an O-glycoside, and the bond is an O-glycosidic link (Figure 7.7). [Note: All sugar–sugar glycosidic bonds are O-type linkages.]

Figure 7.7.Glycosides: examples of N- and O-glycosidic bonds.

Glycosides examples of N- and O-glycosidic bonds

Digestion of Dietary Carbohydrates

The principal sites of dietary carbohydrate digestion are the mouth and intestinal lumen. This digestion is rapid and is catalyzed by enzymes known as glycoside hydrolases (glycosidases) that hydrolyze glycosidic bonds. Because there is little monosaccharide present in diets of mixed animal and plant origin, the enzymes are primarily endoglycosidases that hydrolyze polysaccharides and oliosaccharides, and disaccharidases that hydrolyse tri– and disaccharides into their reducing sugar components (Figure 7.8).

Glycosidases are usually specific for the structure and configuration of the glycosyl residue to be removed, as well as for the type of bond to be broken. The final products of carbohydrate digestion are the monosaccharides, glucose, galactose and fructose, which are absorbed by cells of the small intestine.

Figure 7.8.Hydrolysis of a glycosidic bond.

Hydrolysis of a glycosidic bond

A. Digestion of carbohydrates begins in the mouth

The major dietary polysaccharides are of plant (starch, composed of amylose and amylopectin) and animal (glycogen) origin. During mastication, salivary ?-amylase acts briefly on dietary starch and glycogen, hydrolyzing random ?(1?4) bonds. [Note: There are both ?(1?4)- and ?(1?4)-endoglucosidases in nature, but humans do not produce the latter. Therefore, we are unable to digest cellulose—a carbohydrate of plant origin containing ?(1?4) glycosidic bonds between glucose residues.]

Because branched amylopectin and glycogen also contain ?(1?6) bonds, which ?-amylase cannot hydrolyze, the digest resulting from its action contains a mixture of short, branched and unbranched oligosaccharides known as dextrins (Figure 7.9) [Note: Disaccharides are also present as they, too, are resistant to amylase.] Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates salivary ?-amylase.

Figure 7.9.Degradation of dietary glycogen by salivary or pancreatic ?-amylase.

Degradation of dietary glycogen by salivary or pancreatic ?-amylase

B. Further digestion of carbohydrates by pancreatic enzymes occurs in the small intestine

When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic ?-amylase continues the process of starch digestion.

C. Final carbohydrate digestion by enzymes synthesized by the intestinal mucosal cells

The final digestive processes occur primarily at the mucosal lining of the upper jejunum, and include the action of several disaccharidases (Figure 7.10). For example, isomaltase cleaves the ?(1?6) bond in isomaltose and maltase cleaves maltose and maltotriose, each producing glucose, sucrase cleaves sucrose producing glucose and fructose, and lactase (?-galactosidase) cleaves lactose producing galactose and glucose.

Trehalose, an ?(1?1) disaccharide of glucose found in mushrooms and other fungi, is cleaved by trehalase. These enzymes are secreted through, and remain associated with, the luminal side of the brush border membranes of the intestinal mucosal cells. [Note: The substrates for isomaltase are broader than its name suggests, as it hydrolyzes the majority of maltose.]

Figure 7.10.Digestion of carbohydrates.

Digestion of carbohydrates

[Note: Indigestible cellulose enters the colon and is excreted.]

Sucrase and isomaltase are enzymic activities of a single protein which is cleaved into two functional subunits that remain associated in the cell membrane, forming the sucrase-isomaltase complex. Maltase forms a similar complex with an exoglucosidase (glucoamylase) that cleaves ?(1?4) glycosidic bonds in dextrins

D. Absorption of monosaccharides by intestinal mucosal cells

The duodenum and upper jejunum absorb the bulk of the dietary sugars. However, different sugars have different mechanisms of absorption. For example, galactose and glucose are transported into the mucosal cells by an active, energy-requiring process that requires a concurrent uptake of sodium ions; the transport protein is the sodium-dependent glucose cotransporter 1 (SGLT-1).

Fructose uptake requires a sodium-independent monosaccharide transporter (GLUT-5) for its absorption. All three monosaccharides are transported from the intestinal mucosal cell into the portal circulation by yet another transporter, GLUT-2. (See Specialized functions of GLUT isoforms for a discussion of these transporters.)

E. Abnormal degradation of disaccharides

The overall process of carbohydrate digestion and absorption is so efficient in healthy individuals that ordinarily all digestible dietary carbohydrate is absorbed by the time the ingested material reaches the lower jejunum. However, because it is monosaccharides that are absorbed, any defect in a specific disaccharidase activity of the intestinal mucosa causes the passage of undigested carbohydrate into the large intestine.

As a consequence of the presence of this osmotically active material, water is drawn from the mucosa into the large intestine, causing osmotic diarrhea. This is reinforced by the bacterial fermentation of the remaining carbohydrate to two– and three-carbon compounds (which are also osmotically active) plus large volumes of CO2 and H2 gas, causing abdominal cramps, diarrhea, and flatulence.

1. Digestive enzyme deficiencies

Genetic deficiencies of the individual disaccharidases result in disaccharide intolerance. Alterations in disaccharide degradation can also be caused by a variety of intestinal diseases, malnutrition, or drugs that injure the mucosa of the small intestine. For example, brush border enzymes are rapidly lost in normal individuals with severe diarrhea, causing a temporary, acquired enzyme deficiency. Thus, patients suffering or recovering from such a disorder cannot drink or eat significant amounts of dairy products or sucrose without exacerbating the diarrhea.

2. Lactose intolerance

More than three quarters of the world’s adults are lactose intolerant (Figure 7.11). This is particularly manifested in certain populations. For example, up to 90? are lactase-deficient and, therefore, are less able to metabolize lactose than individuals of Northern European origin. The age-dependent loss of lactase activity represents a reduction in the amount of enzyme rather than a modified inactive enzyme. It is thought to be caused by small variations in the DNA sequence of a region on chromosome 2 that controls expression of the gene for lactase, also on chromosome 2.

Treatment for this disorder is to reduce consumption of milk while eating yogurts and cheeses, as well as green vegetables such as broccoli, to ensure adequate calcium intake; to use lactase-treated products; or to take lactase in pill form prior to eating. [Note: Because the loss of lactase is the norm for most of the world’s adults, use of the term “adult hypolactasia” for lactose intolerance is becoming more common.]

Figure 7.11.Abnormal lactose metabolism.

Abnormal lactose metabolism

3. Sucrase-isomaltase complex deficiency

This deficiency results in an intolerance of ingested sucrose. The disorder is found in about 10? of the Inuit people of Greenland and Canada, whereas 2? of North Americans are heterozygous for the deficiency. Treatment includes the dietary restriction of sucrose, and enzyme replacement therapy.

4. Diagnosis

Identification of a specific enzyme deficiency can be obtained by performing oral tolerance tests with the individual disaccharides. Measurement of hydrogen gas in the breath is a reliable test for determining the amount of ingested carbohydrate not absorbed by the body, but which is metabolized instead by the intestinal flora (see Figure 7.11).

Chapter Summary

Monosaccharides (simple sugars, Figure 7.12) containing an aldehyde group are called aldoses and those with a keto group are called ketoses. Disaccharides, oligosaccharides, and polysaccharides consist of monosaccharides linked by glycosidic bonds. Compounds with the same chemical formula are called isomers. If two monosaccharide isomers differ in configuration around one specific carbon atom (with the exception of the carbonyl carbon), they are defined as epimers of each other.

If a pair of sugars are mirror images (enantiomers), the two members of the pair are designated as d- and l-sugars. When a sugar cyclizes, an anomeric carbon is created from the aldehyde group of an aldose or keto group of a ketose. This carbon can have two configurations, ? or ?. If the aldehyde group on an acyclic sugar gets oxidized as a chromogenic agent gets reduced, that sugar is a reducing sugar. A sugar with its anomeric carbon linked to another structure is called a glycosyl residue.

Sugars can be attached either to an ?NH2 or an –OH group, producing N- and O-glycosides. Salivary ?-amylase acts on dietary polysaccharides (glycogen, amylose, amylopectin), producing oligosaccharides. Pancreatic ?-amylase continues the process of polysaccharide digestion. The final digestive processes occur at the mucosal lining of the small intestine. Several disaccharidases [for example, lactase (?-galactosidase), sucrase, maltase, and isomaltase] produce monosaccharides (glucose, galactose, and fructose).

These enzymes are secreted by and remain associated with the luminal side of the brush border membranes of intestinal mucosal cells. Absorption of the monosaccharides requires specific transporters. If carbohydrate degradation is deficient (as a result of heredity, intestinal disease, malnutrition, or drugs that injure the mucosa of the small intestine), undigested carbohydrate will pass into the large intestine, where it can cause osmotic diarrhea.

Bacterial fermentation of the compounds produces large volumes of CO2 and H2 gas, causing abdominal cramps, diarrhea, and flatulence. Lactose intolerance, caused by a lack of lactase, is by far the most common of these deficiencies.

Figure 7.12.Key concept map for structure of monosaccharides.

Key concept map for structure of monosaccharides