Chapter 12 Carbohydrates

Carbohydrates Carbohydrate: A polyhydroxyaldehyde or polyhydroxyketone, or a substance that gives these compounds on hydrolysis. Monosaccharide: A carbohydrate that cannot be hydrolyzed to a simpler carbohydrate. Monosaccharides have the general formula CnH2nOn, where n varies from 3 to 8. Aldose: A monosaccharide containing an aldehyde group. Ketose: A monosaccharide containing a ketone group.

Monosaccharides The suffix -ose indicates that a molecule is a carbohydrate. The prefixes tri-, tetra, penta, and so forth indicate the number of carbon atoms in the chain. Those containing an aldehyde group are classified as aldoses. Those containing a ketone group are classified as ketoses. There are only two trioses:

Monosaccharides There are only two trioses: Often aldo- and keto- are omitted and these compounds are referred to simply as trioses. Although “triose” does not tell the nature of the carbonyl group, it at least tells the number of carbons.

Monosaccharide Monosaccharides with three carbons: trioses Five carbons: pentose Six carbons: hexose And so on …

Monosacharides Figure 12.1 Glyceraldehyde, the simplest aldose, contains one stereocenter and exists as a pair of enantiomers.

Enantiomers Enantiomers: a molecule has a nonsuperimposable mirror image Chiral molecule – has four different groups

Monosaccharides Fischer projection: A two-dimensional representation for showing the configuration of tetrahedral stereocenters. Horizontal lines represent bonds projecting forward from the stereocenter. Vertical lines represent bonds projecting to the rear. Only the stereocenter is in the plane. (R)-Glyceraldehyde (3-D representation) (R)-Glyceraldehyde (Fisher projection)

Monosacharides In 1891, Emil Fischer made the arbitrary assignments of D- and L- to the enantiomers of glyceraldehyde. D-monosaccharide: the –OH is attached to the bottom-most assymetric center (the carbon that is second from the bottom) is on the right in a Fischer projection.

Monosacharides L-monosaccharide: the -OH is on the left in a Fischer projection.

Table 12.1 Table 20-1 p532

Table 12.2 Table 20-2 p532

Examples Draw Fisher projections for all 2-ketopentoses. Which are D- 2-ketopentoses, which are L-2-ketopentoses? Prefer to table 12.2 (your textbook) to write their names

Amino Sugars Amino sugars contain an -NH2 group in place of an -OH group. Only three amino sugars are common in nature: D-glucosamine, D-mannosamine, and D-galactosamine. N-acetyl-D-glucosamine is an acetylated derivative of D-glucosamine.

Cyclic Structure Aldehydes and ketones react with alcohols to form hemiacetals Cyclic hemiacetals form readily when the hydroxyl and carbonyl groups are part of the same molecule and their interaction can form a five- or six-membered ring.

Epimers Diastereomers that differ in configuration at only on asymmetric center

Haworth Projections Figure 12.2 D-Glucose forms these two cyclic hemiacetals. Same side D-glucose Β-D-Glucopyranose β-D-Glucose -D-Glucopyranose -D-glucose

Haworth Projections A five- or six-membered cyclic hemiacetal is represented as a planar ring, lying roughly perpendicular to the plane of the paper. Groups bonded to the carbons of the ring then lie either above or below the plane of the ring. The new carbon stereocenter created in forming the cyclic structure is called the anomeric carbon. Stereoisomers that differ in configuration only at the anomeric carbon are called anomers. The anomeric carbon of an aldose is C-1; that of the most common ketose is C-2.

Haworth Projections In the terminology of carbohydrate chemistry, A six-membered hemiacetal ring is called a pyranose, and a five- membered hemiacetal ring is called a furanose because these ring sizes correspond to the heterocyclic compounds furan and pyran.

β-2-Deoxy-D-ribofuranose Haworth Projections Aldopentoses also form cyclic hemiacetals. The most prevalent forms of D-ribose and other pentoses in the biological world are furanoses. The prefix “deoxy” means “without oxygen.” at C2 -D-Ribofuranose -D-Ribose β-2-Deoxy-D-ribofuranose Β-2-Deoxy-D-ribose

Haworth Projections D-Fructose (a 2-ketohexose) also forms a five-membered cyclic hemiacetal. -D-Fructofuranose -D-Fructose D-Fructose β-D-Fructofuranose β-D-Fructose

Examples Give structure of the cyclic hemiacetal formed by 4-hydroxybutanal 5-hydroxypentanal

Chair Conformations For pyranoses, the six-membered ring is more accurately represented as a strain-free chair conformation. β-D-Glucopyranose -D-Glucopyranose D-Glucose

Chair Conformations In both Haworth projections and chair conformations, the orientations of groups on carbons 1- 5 of b-D-glucopyranose are up, down, up, down, and up.

Chair Conformations

Examples Which OH groups are in the axial position in β-D-mannopyranose β-D-idopyranose

Mutarotation Mutarotation: The change in specific rotation that accompanies the equilibration of a- and b-anomers in aqueous solution. Example: When either a-D-glucose or b-D-glucose is dissolved in water, the specific rotation of the solution gradually changes to an equilibrium value of +52.7°, which corresponds to 64% beta and 36% alpha forms. β-D-Glucopyranose D-Glucose β-D-Glucopyranose -D-Glucopyranose

Formation of Glycosides Treatment of a monosaccharide, all of which exist almost exclusively in cyclic hemiacetal forms, with an alcohol gives an acetal. Glycosidic bond Glycosidic bond β-D-Glucopyranose β-D-Glucose Methyl β-D-glucopyranoside Methyl β-D-glucoside Methyl -D-glucopyranoside Methyl -D-glucoside

Formation of Glycosides A cyclic acetal derived from a monosaccharide is called a glycoside. The bond from the anomeric carbon to the -OR group is called a glycosidic bond. Mutarotation is not possible for a glycoside because an acetal, unlike a hemiacetal, is not in equilibrium with the open-chain carbonyl-containing compound.

Formation of Glycosides Glycosides are stable in water and aqueous base, but like other acetals, are hydrolyzed in aqueous acid to an alcohol and a monosaccharide. Glycosides are named by listing the alkyl or aryl group bonded to oxygen followed by the name of the carbohydrate in which the ending -e is replaced by - ide.

Examples Draw a Haworth projection and a chair conformation for methyl -D-mannopyranoside. Label the anomeric carbon and glycosidic bond

Reduction to Alditols The carbonyl group of a monosaccharide can be reduced to an hydroxyl group by a variety of reducing agents, including NaBH4 and H2 in the presence of a transition metal catalyst. The reduction product is called an alditol. Alditols are named by changing the suffix -ose to -itol

Alditols The product formed when the CHO group of monosaccharide is reduced to CH2OH group Sorbitol is found in the plant world in many berries and in cherries, plums, pears, apples, seaweed, and algae. It is about 60 percent as sweet as sucrose (table sugar) and is used in the manufacture of candies and as a sugar substitute for diabetics.

Alditols These three alditols are also common in the biological world. Note that only one of these is chiral. Erythritol D-Mannitol Xylitol

Oxidation to Aldonic Acids The aldehyde group of an aldose is oxidized under basic conditions to a carboxylate anion. The oxidation product is called an aldonic acid. A carbohydrate that reacts with an oxidizing agent to form an aldonic acid is classified as a reducing sugar (it reduces the oxidizing agent). Itself is being oxidized

Oxidation to Aldonic Acids 2-Ketoses (e.g. D-fructose) are also reducing sugars.

Oxidation to Aldonic Acids β-D-Glucopyranose D-Glucose D-Gluconate an aldonic acid

Oxidation to Aldonic Acids The body uses glucuronic acid to detoxify foreign alcohols and phenols. These compounds are converted in the liver to glycosides of glucuronic acid and then excreted in the urine. The intravenous anesthetic propofol is converted to the following water-soluble glucuronide and excreted.

Formation of Phosphoric esters

What are Disaccharides and Oligosaccharides? Disaccharide: A carbohydrate containing two monosaccharide units joined by a glycosidic bond Oligosaccharide: A carbohydrate containing from six to ten monosaccharide units, each joined to the next by glycosidic bond Polysaccharide: A carbohydrate consisting of large numbers of monosaccharide units joined by glycosidic bonds.

Sucrose Table sugar, obtained from the juice of sugar cane and sugar beet. -1,2-Glycosidic bond Sucrose

Lactose The principle sugar present in milk. About 5 - 8% in human milk, 4 - 5% in cow’s milk. Has no sweetness β-1,4-Glycosidic bond β-1,4-Glycosidic bond Lactose

Maltose From malt, the juice of sprouted barley and other cereal grains. -1,4-Glycosidic bond Maltose

Polysaccharides Starch: A polymer of D-glucose. Starch can be separated into amylose and amylopectin. Amylose is composed of unbranched chains of up to 4000 D-glucose units joined by a-1,4-glycosidic bonds. Amylopectin contains chains up to 10,000 D-glucose units also joined by a-1,4-glycosidic bonds; at branch points, new chains of 24 to 30 units are started by a- 1,6-glycosidic bonds.

Polysaccharides Figure 12.3 Amylopectin is a branched polymer of D-glucose units joined by a-1,4-glycosidic bonds. Branches consist of D- glucose units that start with an a-1,6-glycosidic bond. -1,6-Glycosidic bond -1,4-Glycosidic bonds

Polysaccharides Glycogen is the energy-reserve carbohydrate for animals. Glycogen is a branched polysaccharide of approximately 106 glucose units joined by a-1,4- and a-1,6-glycosidic bonds. The total amount of glycogen in the body of a well-nourished adult human is about 350 g, divided almost equally between liver and muscle.

Polysaccharides Cellulose is a linear polysaccharide of D-glucose units joined by b-1,4-glycosidic bonds. It has an average molecular weight of 400,000 g/mol, corresponding to approximately 2200 glucose units per molecule. Cellulose molecules act like stiff rods and align themselves side by side into well-organized water-insoluble fibers in which the OH groups form numerous intermolecular hydrogen bonds. This arrangement of parallel chains in bundles gives cellulose fibers their high mechanical strength. It is also the reason why cellulose is insoluble in water.

Polysaccharides Figure 12.4 Cellulose is a linear polysaccharide of D-glucose units joined by b-1,4-glycosidic bonds. β-1,4-Glycosidic bonds

Polysaccharides Cellulose (cont’d) Humans and other animals can not digest cellulose because their digestive systems do not contain b-glycosidases, enzymes that catalyze the hydrolysis of b-glycosidic bonds. Termites have such bacteria in their intestines and can use wood as their principal food. Ruminants (cud-chewing animals) and horses can also digest grasses and hay. Humans have only a-glucosidases; hence, the polysaccharides we use as sources of glucose are starch and glycogen. Many bacteria and microorganisms have b-glucosidases.

Example Draw a chair conformation for a disaccharide in which two units of D-glucopyranose are joined by a β -1,3-glycosidic bond

Acidic Polysaccharides Acidic polysaccharides: a group of polysaccharides that contain carboxyl groups and/or sulfuric ester groups, and play important roles in the structure and function of connective tissues. There is no single general type of connective tissue. Rather, there are a large number of highly specialized forms, such as cartilage, bone, synovial fluid, skin, tendons, blood vessels, intervertebral disks, and cornea. Most connective tissues are made up of collagen, a structural protein, in combination with a variety of acidic polysaccharides.

Acidic Polysaccharides Heparin (cont’d) Heparin is synthesized and stored in mast cells of various tissues, particularly the liver, lungs, and gut. The best known and understood of its biological functions is its anticoagulant activity. It binds strongly to antithrombin III, a plasma protein involved in terminating the clotting process.

Heparin Figure 12.5 The repeating pentasaccharide unit of heparin.

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