Chapter 3:

CARBOHYDRATES

OUTLINE
I. Carbohydrates Overview II. Monosaccharides III. Cyclic Structures of Monosaccharides IV. Reactions of Monosaccharides V. Disaccharides VI. Oligosaccharides VII.Acidic Polysaccharides VIII.Structure and Roles of Polysaccharides IX. Chemical Connections

Chem 3 Intro to Biochemistry

Carbohydrates
the most abundant organic chemical in the plant world
Each year, photosynthesis converts more than 100 billion metric tons of CO2 and H2O into cellulose and other plant products. act as storehouses of chemical energy (glucose, starch, glycogen) components of supportive structures in plants (cellulose), crustacean shells (chitin), and connective tissues in animals (acidic polysaccharides) essential components of nucleic acids (D-ribose and 2deoxy-D-ribose)
Chem 3 Intro to Biochemistry

A. Structure and Nomenclature

Carbohydrates means hydrates of carbon
molecular formula (CH2O)n = (C . H2O)n where n 3 or Cn(H2O)m

ex.

Glucose (blood sugar): C6H12O6

can also be written as

C6(H2O)6

Sucrose (table sugar): C12H22O11

can also be written as

C12(H2O)11
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CARBOHYDRATES
are polyhydroxyaldehydes, polyhydroxyketones, and their derivatives all carbons attached to an oxygen

originate from solar-powered combination of CO2 + H2O in plants (photosynthesis)

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 saccharide derived from the Greek sakcharon; 6 Latin saccharum, meaning sugar.

MONOSACCHARIDES
have the general formula CnH2nOn one of the carbons being the carbonyl group of either an aldehyde or a ketone the suffix ose indicates that the molecule is a carbohydrates

Prefixes tri-, tetra-, pent, etc indicate the number of carbon atoms in the chain.
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 Name the each of the following monosaccharides as an aldose or a ketose, and name each according to the number of carbon atoms.

(a)

(b)

(c)

Draw the structures of an aldotetrose and a ketopentose.

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B. Fischer Projection Formulas

devised by Hermann Emil Fischer in 1891

is a two-dimensional representation of a threedimensional organic molecule by projection.

commonly designated using D,L system w/c is very common for sugars D,L designation refers to the configuration of the highest-numbered asymmetric center
D,L only refers the stereocenter of interest back to D- and L glyceraldehyde D,L do not specify the sign of rotation of planepolarized light (that is d and l) 11

FISCHER PROJECTIONS

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D-glyceraldehydes (hydroxyl group at the highest numbered asymmetric carbon atom is written to the right): L-glyceraldehydes (hydroxyl group at the highest numbered asymmetric carbon atom is written to the left): D-Erythrose is the mirror image of L-Erythrose.

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 Draw Fischer projections for the four aldotetroses. Which are D-monosaccharides, which are Lmonosaccharides, and which are enantiomers? Based on the structure below, write the name of each aldotetrose.

(a)

(b)

(c)

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Draw Fischer projections for all 2-ketopentoses. Which are d-2-ketopentoses, which are L-2-ketopentoses, and which are enantiomers?

Based on the structure below, write the write the name of each 2-ketopentose.

(a)

(b)

(c)

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C. D- and L- Monosaccharides
D-monosaccharide has the same configuration at its penultimate carbon as D-glyceraldehyde (its -OH group is on the right) in a Fischer projection

L-monosaccharide has the same configuration at its penultimate carbon as L-glyceraldehyde (its -OH group is on the left).
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Aldotriose

Aldotetrose

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Aldopentose

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Aldohexose

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Note C numbering

1 2 3 4

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THREE MOST ABUNDANT HEXOSES

1. D-glucose
Glucose, also known as dextrose, is found in large quantities throughout the living world. It is the primary fuel for living cells. In animals, glucose is the is the preferred energy source of brain cells and cell that have few or no mitochondria, such a erythrocytes. Cells that have a limited oxygen supply, such as those in the eyeball, also use large amounts of glucose to generate energy. Dietary sources include plant starch and the disaccharides lactose, maltose and sucrose.
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THREE MOST ABUNDANT HEXOSES

2. D-galactose
Galactose is neccesary to synthesize a variety of biomolecules. These include lactose (in lactating mammary glands), glycolipids, certain phospholipids, proteoglycans, and glycoproteins. Synthesis of these substance is not diminished by diets that lack galactose of the disaccharide
lactose .

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THREE MOST ABUNDANT HEXOSES

3. D-fructose
Fructose, or levulose, is often referred to as fruit sugar because of its high content in fruit. It is also found in some vegetables as well as in honey. This molecules is an important member of the ketose family of sugars. On a per gram basis, fructose is twice as sweet as sucrose. It can therefore be used in smaller amounts. For this reason, fructose is often used as sweetening agent in processed food products. Large amounts of fructose are used in the male reproductive tract. It is synthesized in the seminal vesicles and then incorporated into semen. Sperm use the sugar as an energy source.
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Two sugars that differ in configuration at only one chiral center are epimers

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D. Amino Sugars
are monosaccharides in which an OH group is replaced by an NH2 group

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D. Amino Sugars
Only three amino sugars are common in nature: D-glucosamine, D-mannosamine, and D-galactosamine. N- Acetyl-D-glucosamine, a derivative of Dglucosamine, is a component of many polysaccharides, including connective tissue such as cartilage. It is also a component of chitin, the hard, shelllike exoskeleton of lobsters, crabs, shrimp, and other shellfish.
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E. Physical Properties of Monosaccharides

Monosaccharides are colorless, crystalline solids. All monosaccharides are very soluble in water because hydrogen bonding is possible between their polar -OH groups and water. They are only slightly soluble in ethanol. Insoluble in nonpolar solvents such as diethyl ether, dichloromethane, and benzene.

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Cyclic Structures of Monossacharides

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Cyclic Structures of Monossacharides

Note cyclic hemiacetals form very readily when hydroxyl and carbonyl groups are part of the same molecule and that their interaction produces a ring. 4-hydroxypentanal contains one stereocenter and that hemiacetal formation generates a second stereocenter at 36 carbon 1.

A. Haworth Projections

common way of representing the cyclic structure of monosaccharide named after Sir Walter N. Haworth (1937)
in a Haworth projection, a five or six-membered cyclic hemiacetal is represented as a planar pentagon or hexagon, respectively, 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.

A. Haworth Projections

named after Sir Walter N. Haworth (1937)

A. Haworth Projections
Anomeric Carbon - the carbon atom which is involved in hemiacetal or acetal formation. The new carbon stereocenter created in forming the cyclic structure. Anomers - stereoisomers formed when ring is formed (, ).
Typically, Haworth projections are most commonly drawn with the anomeric carbon to the right and the hemiacetal oxygen to the back.

A. Haworth Projections
In the terminology of carbohydrate chemistry,
means that the -OH on the anomeric carbon of the cyclic hemiacetal lies on the same side of the ring as the terminal -CH2OH

means that the -OH on the anomeric carbon of the cyclic hemiacetal lies on the side of the ring opposite from the terminal -CH2OH. The and anomers of D-glucose interconvert in aqueous solution by a process called mutarotation.

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A. Haworth Projections
The terms furanose and pyranose are used because monosaccharide five- and six- membered rings correspond to the heterocyclic compounds furan and pyran.

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Aldopentoses Cyclic Conformation

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 Draw Haworth projections for the and anomers of D-galactopyranose.

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Draw Haworth projections for the and anomers of D-galactopyranose.

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 The open-chain form of D-altrose, an aldohexose isomer of glucose, has the following structure. Draw D-altrose in its cyclic hemiacetal form:

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 The cyclic structure of D-mannose, an aldohexose, is drawn below. Convert this to the straight-chain Fischer projection structure.

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Ketohexoses Cyclic Formation

Ketohexoses also occur in and anomeric forms. In these compounds the hydroxyl group at C-5 (or C-6) reacts with the keto group at C-2, forming a furanose (or pyranose) ring containing a hemiketal linkage

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B. Chair conformation

-D-glucopyranose each group including the anomeric OH group is equatorial. -D-glucopyranose - the anomeric OH group is axial.

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Comparing the relative orientations of groups on the D-glucopyranose ring in the Haworth projection and the chair conformation.

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 Given the Fischer projection of the D-galactose, draw chair conformations for -Dgalactopyranose and -D-galactopyranose. Label the anomeric carbon in each.

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 Given the Fischer projection of the D-galactose, draw chair conformations for -Dgalactopyranose and -D-galactopyranose. Label the anomeric carbon in each.

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C. Mutarotation
the change in specific rotation that accompanies the equilibration of and anomers in aqueous solution.

The equilibrium mixture consists of 64% -D-glucopyranose and 36% -D-glucopyranose, with only a trace (0.003%) of the open-chain form. Mutarotation is common to all carbohydrates that exist in hemiacetal forms. 57

The most stable form of glucose is -D glucose.

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REACTIONS OF MONOSACCHARIDES
A. Formation of Glycosides (Acetals) B. Reduction to Alditols C. Oxidation to Aldonic Acids (Reducing Sugars) D. Oxidation to Uronic Acids E. Formation of Phosphoric Esters
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A. Formation of Glycosides (Acetals)

Review Treatment of aldehyde or ketone with one molecule of alcohol yields a hemiacetal.

Hemiacetal a molecule containing a carbon bonded to one OH group and one OR group.

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A. Formation of Glycosides (Acetals)

Review Hemiacetals can react further with alcohols to form acetals plus water.

Acetal a molecule containing two OR groups bonded to the same carbon.

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A. Formation of Glycosides (Acetals)

Treatment of a monosaccharide all forms of which exist almost exclusively as cyclic hemiacetals with an alcohol also yields an acetal.

Glycoside - a carbohydrate in which the --OH group on its anomeric carbon is replaced by an --OR group. Glycosidic bond - the bond from the anomeric carbon of a glycoside 62 to OR group.

A. Formation of Glycosides (Acetals)

Mutarotation is not possible in a glycoside because an acetalunlike a hemiacetalis no longer in equilibrium with the open-chain carbonyl containing compound. Glycosides are stable in water and aqueous base; like other acetals, however, they are hydrolyzed in aqueous acid to an alcohol and a monosaccharide.

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Example : Finding the Anomeric Carbon and Glycosidic Bond

Draw the structural formula for methyl -D-ribofuranoside (methyl -D-riboside). Label the anomeric carbon and the glycosidic bond.

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FOLLOW UP PROBLEM
Draw a Haworth projection and a chair conformation for methyl -D-mannopyranoside (methyl -D-mannoside). Label the anomeric carbon and the glycosidic bond.

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B. Reduction to Alditols
The carbonyl group of a monosaccharide can be reduced to a hydroxyl group by a variety of reducing agents, including hydrogen in the presence of a transition metal catalyst and sodium borohydride.

Alditols the product formed when the CHO group of a monosaccharide is reduced to a CH2OH group

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B. Reduction to Alditols
We name alditols by dropping the -ose from the name of the monosaccharide and adding -itol. Reduction of D-glucose gives Dglucitol, more commonly known as D-sorbitol. Sorbitol is found in the plant world in many berries and in cherries, plums, pears, apples, seaweed, and algae. It is about 60% as sweet as sucrose (table sugar) and is used in the manufacture of candies and as a sugar substitute for diabetics.

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B. Reduction to Alditols
Other alditols commonly found in the biological world

Xylitol is used as a sweetening agent in sugarless gum, candy, and sweet cereals.
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C. Oxidation to Aldonic Acids (Reducing Sugars)

Review Aldehydes (RCHO) are oxidized to carboxylic acids (RCOOH) by several agents, including oxygen, O2.

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C. Oxidation to Aldonic Acids (Reducing Sugars)

The aldehyde group of an aldose can be oxidized, under basic conditions, to a carboxylate group.

Any carbohydrate that reacts with an oxidizing agent to form an aldonic acid is classified as a reducing sugar (it reduces the oxidizing agent).
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C. Oxidation to Aldonic Acids (Reducing Sugars)

2-ketoses are also reducing sugars but carbon 1 (a CH2OH) of ketose is not oxidized directly. Instead, a 2-ketose exists in equilibrium with an aldose by way of an enediol intermediate.

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D. Oxidation to Uronic Acids

Enzyme-catalyzed oxidation of the primary alcohol at carbon 6 of a hexose yields a uronic acid.

D-glucuronic acid is widely distributed in both the plant and animal worlds.

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D. Oxidation to Uronic Acids

In humans, D-glucuronic acids serves as an important component of the acidic polysaccharides of connective tissues. The body also uses D-glucuronic acid to detoxify foreign phenols and alcohols. In the liver, these compounds are converted to glycosides of glucuronic acid (glucuronides) and excreted in the urine. The intravenous anesthetic propofol, for example, is converted to the following glucuronide and then excreted in urine:

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E. The Formation of Phosphoric Esters

In the synthesis and metabolism of carbohydrates, the intermediates are very often not the sugars themselves but their phosphorylated derivatives. Condensation of phosphoric acid with one of the hydroxyl groups of a sugar forms a phosphate ester, as in glucose 6phosphate. Sugar phosphates are relatively stable at neutral pH and bear a negative charge. One effect of sugar phosphorylation within cells is to trap the sugar inside the cell; most cells do not have plasma membrane transporters for phosphorylated sugars. Phosphorylation also activates sugars for subsequent chemical transformation.
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E. The Formation of Phosphoric Esters

Mono- and diphosphoric esters are important intermediates in the metabolism of monosaccharides.

D-glucuronic acid is widely distributed in both the plant and animal worlds.

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DISACCHARIDES and OLIGOSACCHARIDES

Most carbohydrates in nature contain more than one monosaccharide unit.

Disaccharides

a carbohydrate containing monosaccharide units joined by a glycosidic bond.

two

Oligosaccharides - a carbohydrate containing from six to

ten monossacharide units, each joined to the next by a glycosidic bond

Polysaccharide - a carbohydrate containing a large number

of monosaccharide units, each joined to the next by one or more glycosidic bonds
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DISACCHARIDES
are carbohydrates containing 2 monossacharide units joined together by glycosidic bond with the loss of water.

Disaccharides
Maltose Lactose Sucrose

Sources
Germinating grains, starch hydrolysis Milk, yogurt, ice cream Sugar cane, sugar beets

Monosaccharides
Glucose + glucose Glucose + galactose Glucose + fructose

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A. Sucrose

DISACCHARIDES

Sucrose (table sugar) is the most abundant disaccharide in the biological world. It is obtained principally from the juice of sugar cane and sugar beets.
In sucrose, carbon 1 of -D-glucopyranose bonds to carbon 2 of D-fructofuranose by an -1,2-glycosidic bond. Because the anomeric carbons of both the glucopyranose and fructofuranose units are involved in formation of the glycosidic bond, neither monosaccharide unit is in equilibrium with its open-chain form. Thus sucrose is a nonreducing sugar. In the production of sucrose, sugar cane or sugar beet is boiled with water, and the resulting solution is cooled. Sucrose crystals separate and are collected. Subsequent boiling to concentrate the solution followed by cooling yields a dark, thick 78 syrup known as molasses.

A. Sucrose

DISACCHARIDES

Monossacharide: GLUCOSE-FRUCTOSE
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B. Lactose

DISACCHARIDES

Lactose is the principal sugar present in milk. It accounts for 5 to 8% of human milk and 4 to 6% of cows milk. This disaccharide consists of D-galactopyranose bonded by a -1,4-glycosidic bond to carbon 4 of Dglucopyranose. Lactose is a reducing sugar, because the cyclic hemiacetal of the D-glucopyranose unit is in equilibrium with its open-chain form and can be oxidized to a carboxyl group.

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B. Lactose

DISACCHARIDES

Monossacharide: GALACTOSE-GLUCOSE
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C. Maltose

DISACCHARIDES

Maltose derives its name from its presence in malt, the juice from sprouted barley and other cereal grains. It consists of two units of D-glucopyranose joined by a glycosidic bond between carbon 1 (the anomeric carbon) of one unit and carbon 4 of the other unit.
Because the oxygen atom on the anomeric carbon of the first glucopyranose unit is alpha, the bond joining the two units is an a-1,4-glycosidic bond. Following are a Haworth projection and a chair conformation for -maltose, so named because the -OH groups on the anomeric carbon of the glucose unit on the right are beta. 82

C. Maltose

DISACCHARIDES

Monossacharide: GLUCOSE-GLUCOSE
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D. Relative Sweetness

DISACCHARIDES

The sweet taste of honey is due largely to D-fructose and D-glucose. Lactose has almost no sweetness and is sometimes added to foods as a filler. Some people cannot tolerate lactose well, however, and should avoid these foods. 84

Example: Drawing Chair Conformations for a Disaccharide

Draw a chair conformation for the anomer of a disaccharide in which two units of D-glucopyranose are joined by an -1,6-glycosidic bond.

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FOLLOW UP PROBLEM
Draw a chair conformation for the a form of a

disaccharide in which two units of D-glucopyranose are joined by a -1,3-glycosidic bond.

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POLYSACCHARIDES
Most carbohydrates found in nature occur as polysaccharides, polymers of medium to high molecular weight. Polysaccharides, also called glycans, differ from each other in the identity of their:
recurring monosaccharide units, in the length of their chains, in the types of bonds linking the units, and in the degree of branching.
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POLYSACCHARIDES
are long-chain polymers that contain large numbers of monosaccharides (usually glucose units) joined together by glycosidic bonds. Polysaccharides Starch (amylose, amylopectin
Glycogen

Sources Rice, wheat, grains, cereals

Muscle, liver

Monosaccharides Glucose
Glucose

Cellulose

wood, plants,
paper, cotton

Glucose
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POLYSACCHARIDES

A. Starch: Amylose and Amylopectin

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POLYSACCHARIDES

A. Starch: Amylose and Amylopectin

Starch is used for energy storage in plants. It is found in all plant seeds and tubers and is the form in which glucose is stored for later use. Most starches contain 20 to 25% amylose and 75 to 80% amylopectin. Complete hydrolysis of both amylose and mylopectin yields only D-glucose.

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A. Starch: Amylose

POLYSACCHARIDES

Amylose is composed of continuous, unbranched chains of as many as 4000 D-glucose units joined by -1,4glycosidic bonds.

A short segment of amylose, a linear polymer of D-glucose residues in (14) linkage. A single chain can contain several thousand glucose residues 91 to more than a million.

POLYSACCHARIDES

A. Starch: Amylopectin

Amylopectin has a high molecular weight (up to 100 million) but unlike amylose is highly branched. The glycosidic linkages joining successive glucose residues in amylopectin chains are (14); the branch points (occurring every 24 to 30 residues) are ( 1 6) linkages. 92

POLYSACCHARIDES

B. Glycogen

Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass Glycogen is a polymer of glucose; similar to starch; also contains (14) and (16) glycosidic bond Only difference from starch: number of branches; it is more extensively branched 93 (16) branches every 8-12 residues

POLYSACCHARIDES

C. Cellulose
Cellulose is the most abundant natural polymer on earth The most widely distributed plant skeletal polysaccharide, constitutes almost half of the cellwall material of wood. The principal strength and support for trees and plants Can also be soft and fuzzy (Ex. cotton is almost pure cellulose)
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POLYSACCHARIDES

C. Cellulose
Cellulose molecules act much like stiff rods, a characteristic that enables them to 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 also explains why cellulose is insoluble in water. When a piece of cellulose-containing material is placed in water, there are not enough -OH groups on the surface of the fiber to pull individual cellulose molecules away from the strongly hydrogen-bonded fiber.
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POLYSACCHARIDES

C. Cellulose
(14) linkages make a big difference

Interchain H-bonding and intrasheet H-bonding produce supramolecular fiber of great tensile strength

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C. Cellulose

POLYSACCHARIDES

Humans and other animals cannot use cellulose as food because our digestive systems do not contain glucosidases, enzymes that catalyze the hydrolysis of -glucosidic bonds. Instead, we have only -glucosidases; hence, we use the polysaccharides starch and glycogen as sources of glucose. Glycogen and starch ingested in the diet are hydrolyzed by -amylases, enzymes in saliva and intestinal secretions that break (14) glycosidic bonds between glucose units.
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C. Cellulose

POLYSACCHARIDES

Many bacteria and microorganisms do contain glucosidases and so can digest cellulose. Termites (much to our regret) 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 because glucosidase-containing microorganisms are present in their alimentary systems.

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Acidic Polysaccharides
Acidic polysaccharides are a group of polysaccharides that contain carboxyl groups and/or sulfuric ester groups. Acidic polysaccharides play important roles in the structure and function of connective tissues. Because they contain amino sugars, a more current name for these substances is glycosaminoglycans. Most connective tissues consist of collagen, a structural protein, combined with a variety of acidic polysaccharides (glycosaminoglycans) that interact with collagen to form tight or loose networks.
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A. Hyaluronic Acid
Hyaluronic acid is the simplest acidic polysaccharide present in connective tissue. It has a molecular weight of between 105 and 107 g/mol and contains from 300 to 100,000 repeating units, depending on the organ in which it occurs. It is most abundant in embryonic tissues and in specialized connective tissues such as synovial fluid, the lubricant of joints in the body, and the vitreous of the eye, where it provides a clear, elastic gel that holds the retina in its proper position. Hyaluronic acid is also a common ingredient in lotions, moisturizers, and cosmetics. 101

A. Hyaluronic Acid
Hyaluronic acid is composed of D-glucuronic acid joined by a b-1,3- glycosidic bond to N-acetyl-D-glucosamine, which is in turn linked to D-glucuronic acid by a b-1,4-glycosidic bond.

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B. Heparin
Heparin is a heterogeneous mixture of variably sulfonated polysaccharide chains, ranging in molecular weight from 6000 to 30,000 g/mol.
This acidic polysaccharide is synthesized and stored in mast cells (cells that are part of the immune system and that occur in several types of tissues) of various tissuesparticularly the liver, lungs, and gut. Heparin has many biological functions, the best known and fully understood of which is its anticoagulant activity. It binds strongly to antithrombin III, a plasma protein involved in terminating the clotting process.
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B. Heparin
A heparin preparation with good anticoagulant activity contains a minimum of eight repeating units. The larger the molecule, the greater its anticoagulant activity. Because of this anticoagulant activity, it is widely used in medicine.

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- a linear homopolysaccharide composed of N-acetylglucosamine residues in 105 linkage

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