Berg J.M., Tymoczko J.L., Stryer L. Biochemistry

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Figure 11.3.

d -Ketoses containing three- four, five, and six carbon atoms. The keto group is shown in blue. The

asymmetric center farthest from the keto group, which determines the d designation, is shown in red.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.4. Pyranose Formation. The open-chain form of glucose cyclizes when the C-5 hydroxyl group attacks the

oxygen atom of the C-1 aldehyde group to form an intramolecular hemiacetal. Two anomeric forms, designated α and β ,

can result.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.5. Furanose Formation. The open-chain form of fructose cyclizes to a five-membered ring when the C-5

hydroxyl group attacks the C-2 ketone to form an intramolecular hemiketal. Two anomers are possible, but only the α

anomer is shown.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.6. Ring Structures of Fructose. Fructose can form both five-membered furanose and six-membered pyranose

rings. In each case, both α and β anomers are possible.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.7. Chair and Boat Forms of β -

d -glucopyranose. The chair form is more stable because of less steric

hindrance as the axial positions are occupied by hydrogen atoms.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.8. Envelope Conformations of β - d -ribose. The C

-endo and C

-endo forms of β -d-ribose are shown. The

color indicates the four atoms that lie approximately in a plane.

I. The Molecular Design of Life 11. Carbohydrates 11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Figure 11.9. Modified Monosaccharides. Carbohydrates can be modified by the addition of substituents (shown in red)

other than hydroxyl groups. Such modified carbohydrates are often expressed on cell surfaces.

I. The Molecular Design of Life 11. Carbohydrates

11.2. Complex Carbohydrates Are Formed by Linkage of Monosaccharides

Because sugars contain many hydroxyl groups, glycosidic bonds can join one monosaccharide to another.

Oligosaccharides are built by the linkage of two or more monosaccharides by O-glycosidic bonds (Figure 11.10). In

maltose, for example, two d-glucose residues are joined by a glycosidic linkage between the α -anomeric form of C-1 on

one sugar and the hydroxyl oxygen atom on C-4 of the adjacent sugar. Such a linkage is called an α -1,4-glycosidic

bond. The fact that monosaccharides have multiple hydroxyl groups means that various glycosidic linkages are possible.

Indeed, the wide array of these linkages in concert with the wide variety of monosaccharides and their many isomeric

forms makes complex carbohydrates information-rich molecules.

11.2.1. Sucrose, Lactose, and Maltose Are the Common Disaccharides

A disaccharide consists of two sugars joined by an O-glycosidic bond. Three abundant disaccharides are sucrose,

lactose, and maltose (Figure 11.11). Sucrose (common table sugar) is obtained commercially from cane or beet. The

anomeric carbon atoms of a glucose unit and a fructose unit are joined in this disaccharide; the configuration of this

glycosidic linkage is α for glucose and β for fructose. Sucrose can be cleaved into its component monosaccharides by the

enzyme sucrase.

Lactose, the disaccharide of milk, consists of galactose joined to glucose by a β-1,4-glycosidic linkage. Lactose is

hydrolyzed to these monosaccharides by lactase in human beings (Section 16.1.12) and by β-galactosidase in bacteria.

In maltose, two glucose units are joined by an α -1,4 glycosidic linkage, as stated earlier. Maltose comes from the

hydrolysis of starch and is in turn hydrolyzed to glucose by maltase. Sucrase, lactase, and maltase are located on the

outer surfaces of epithelial cells lining the small intestine (Figure 11.12).

11.2.2. Glycogen and Starch Are Mobilizable Stores of Glucose

Large polymeric oligosaccharides, formed by the linkage of multiple monosaccharides, are called polysaccharides.

Polysaccharides play vital roles in energy storage and in maintaining the structural integrity of an organism. If all of the

monosaccharides are the same, these polymers are called homopolymers. The most common homopolymer in animal

cells is glycogen, the storage form of glucose. As will be considered in detail in Chapter 21, glycogen is a very large,

branched polymer of glucose residues. Most of the glucose units in glycogen are linked by α -1,4-glycosidic bonds. The

branches are formed by α -1,6-glycosidic bonds, present about once in 10 units (Figure 11.13).

The nutritional reservoir in plants is starch, of which there are two forms. Amylose, the unbranched type of starch,

consists of glucose residues in α -1,4 linkage. Amylopectin, the branched form, has about 1 α -1,6 linkage per 30 α -1,4

linkages, in similar fashion to glycogen except for its lower degree of branching. More than half the carbohydrate

ingested by human beings is starch. Both amylopectin and amylose are rapidly hydrolyzed by α-amylase, an enzyme

secreted by the salivary glands and the pancreas.

11.2.3. Cellulose, the Major Structural Polymer of Plants, Consists of Linear Chains of

Glucose Units

Cellulose, the other major polysaccharide of glucose found in plants, serves a structural rather than a nutritional role.

Cellulose is one of the most abundant organic compounds in the biosphere. Some 10

kg of cellulose is synthesized and

degraded on Earth each year. It is an unbranched polymer of glucose residues joined by β-1,4 linkages. The β

configuration allows cellulose to form very long, straight chains. Fibrils are formed by parallel chains that interact with

one another through hydrogen bonds. The α-1,4 linkages in glycogen and starch produce a very different molecular

architecture from that of cellulose. A hollow helix is formed instead of a straight chain (Figure 11.14). These differing

consequences of the α and β linkages are biologically important. The straight chain formed by β linkages is optimal for

the construction of fibers having a high tensile strength. In contrast, the open helix formed by α linkages is well suited to

forming an accessible store of sugar. Mammals lack cellulases and therefore cannot digest wood and vegetable fibers.

11.2.4. Glycosaminoglycans Are Anionic Polysaccharide Chains Made of Repeating

Disaccharide Units

A different kind of repeating polysaccharide is present on the animal cell surface and in the extracellular matrix. Many

glycosaminoglycans are made of disaccharide repeating units containing a derivative of an amino sugar, either

glucosamine or galactosamine (Figure 11.15). At least one of the sugars in the repeating unit has a negatively charged

carboxylate or sulfate group. Chondroitin sulfate, keratan sulfate, heparin, heparan sulfate, dermatan sulfate, and

hyaluronate are the major glycosaminoglycans.

Glycosaminoglycans are usually attached to proteins to form proteoglycans. Heparin is synthesized in a nonsulfated

form, which is then deacet-ylated and sulfated. Incomplete modification leads to a mixture of variously sulfated

sequences. Some of them act as anticoagulants by binding specifically to antithrombin, which accelerates its

sequestration of thrombin (Section 10.5.6). Heparan sulfate is like heparin except that it has fewer N- and O-sulfate

groups and more acetyl groups.

Proteoglycans resemble polysaccharides more than proteins in as much as the carbohydrate makes up as much as 95% of

the biomolecule by weight. Proteoglycans function as lubricants and structural components in connective tissue, mediate

adhesion of cells to the extracellular matrix, and bind factors that stimulate cell proliferation.

11.2.5. Specific Enzymes Are Responsible for Oligosaccharide Assembly

Oligosaccharides are synthesized through the action of specific enzymes, glycosyltransferases, which catalyze the

formation of glycosidic bonds. Each enzyme must be specific, to a greater or lesser extent, to the sugars being linked.

Given the diversity of known glycosidic linkages, many different enzymes are required. Note that this mode of assembly

stands in contrast with those used for the other biological polymers heretofore discussed that is, polypeptides and

oligonucleotides. As these polymers are assembled, information about monomer sequence is transferred from a template,

and a single catalytic apparatus is responsible for all bond formation.

The general form of the reaction catalyzed by a glycosyltransferase is shown in Figure 11.16. The sugar to be added

comes in the form of an activated sugar nucleotide. Sugar nucleotides are important intermediates in many processes,

and we will encounter these intermediates again in Chapters 16 and 21. Note that such reactions can proceed with either

retention or inversion of configuration at the glycosidic carbon atom at which the new bond is formed; a given enzyme

proceeds by one stereochemical path or the other.

The human ABO blood groups illustrate the effects of glycosyl- transferases. Carbohydrates are attached to

glycoproteins and glycolipids on the surfaces of red blood cells. For one type of blood group, one of the three

different structures, termed A, B, and O, may be present (Figure 11.17). These structures have in common an

oligosaccharide foundation called the O (or sometimes H) antigen. The A and B antigens differ from the O antigen by

the addition of one extra monosaccharide, either N-acetylgalactosamine (for A) or galactose (for B) through an α -1,3

linkage to a galactose moiety of the O antigen.

Specific glycosyltransferases add the extra monosaccharide to the O antigen. Each person inherits the gene for one

glycosyltransferase of this type from each parent. The type A transferase specifically adds N-acetylgalactosamine,

whereas the type B transferase adds galactose. These enzymes are identical in all but 4 of 354 positions. The O

phenotype is the result of a mutation that leads to premature termination of translation and, hence, to the production of

no active glycosyltransferase.

These structures have important implications for blood transfusions and other transplantation procedures. If an antigen

not normally present in a person is introduced, the person's immune system recognizes it as foreign. Adverse reactions

can ensue, initiated by the intravascular destruction of the incompatible red blood cells.

Why are different blood types present in the human population? Suppose that a pathogenic organism such as a

parasite expresses on its cell surface a carbohydrate antigen similar to one of the blood-group antigens. This

antigen may not be readily detected as foreign in a person with the blood type that matches the parasite antigen, and the

parasite will flourish. However, other people with different blood types will be protected. Hence, there will be selective

pressure on human beings to vary blood type to prevent parasitic mimicry and a corresponding selective pressure on

parasites to enhance mimicry. The constant "arms race" between pathogenic microorganisms and human beings drives

the evolution of diversity of surface antigens within the human population.