Chapter 14 Biomolecules: Carbohydrates Suggested Problems: 27,31-4,36-7,43,46-7

Importance of Carbohydrates Distributed widely in nature Key intermediates of metabolism (sugars) Structural components of plants (cellulose) Central to materials of industrial products: paper, lumber, fibers Key component of food sources: sugars, flour, vegetable fiber Contain OH groups on most carbons in linear chains or in rings

Chemical Formula and Name Carbohydrates have roughly as many O’s as C’s (highly oxidized) The empirical formulas are roughly (C(H2O))n Appears to be “carbon hydrate” from formula

Sources Glucose is produced in plants through photosynthesis from CO2 and H2O Glucose is converted in plants to other small sugars and polymers (cellulose, starch) Dietary carbohydrates provide the major source of energy required by organisms

14.1 Classification of Carbohydrates Simple sugars (monosaccharides) can't be converted into smaller sugars by hydrolysis. Complex carbohydrates are made of two or more simple sugars connected as acetals (aldehyde and alcohol), oligosaccharides, and polysaccharides Sucrose (table sugar): disaccharide from two monosaccharides (glucose linked to fructose), Cellulose is a polysaccharide of several thousand glucose units connected by acetal linkages (aldehyde and alcohol) Disaccharides: lactose galactose and glucose; sucrose fructose and glucose; maltose glucose and glucose Enzyme linked hydrolysis converts polysaccharides into their constituent monosaccharides

Aldoses and Ketoses aldo- and keto- prefixes identify the nature of the carbonyl group -ose suffix designates a carbohydrate Number of C’s in the monosaccharide indicated by root (tri-, tet-, pent-, hex-)

14.2 Depicting Carbohydrate Stereochemistry: Fischer Projections Carbohydrates have multiple chirality centers A chirality center C is projected into the plane of the paper and other groups are on horizontal or vertical lines Groups forward from paper are always in a horizontal line. Groups back from the paper are always in a vertical line. The oxidized end of the molecule is always higher on the page (“up”) Fischer projections are a good way to represent molecules with numerous chirality centers.

Stereochemical Reference Stereochemistry reference compounds are the two enantiomers of glyceraldehyde, C3H6O3 A compound is “D” if the hydroxyl group at the chirality center farthest from the oxidized end of the sugar is on the right or “L” if it is on the left. D-glyceraldehyde is (R)-2,3-dihydroxypropanal L-glyceraldehyde is (S)-2,3-dihydroxypropanal The OH above the CH2OH group points to the right – D configuration

Stereochemical Reference Carbohydrates with more than one stereocenters are shown in Fischer projection by stacking one center on top of the other The molecules true three-dimensional conformation is one that is curled around itself like a bracelet The bracelet sets the molecule up for form a hemiacetal. D-

Working With Fischer Projections In determining R, S designations place the lowest priority group on the vertical axis (to the back) With the lowest priority group to the back, prioritize the 3 highest groups – clockwise is R; counterclockwise is S Switching any two groups changes R to S and vice versa Switching any two groups again returns the original configuration.

Naturally Occurring D Sugars Most have the —OH group at the bottom chirality center pointing to the right Have an R configuration at the lowest chirality center D sugars are typically what is found in nature. They have the R configuration at the lowest chiral center. While glyceraldehyde rotates light in a positive direction, there is no correlation between between D and L and (+) and (-). The D configuration designation comes because Glyceraldehyde was the first sugar to have its rotation measured. The D refers to the configuration at the bottommost chiral center.

L Sugars Most have the —OH group at the bottom chirality center pointing to the left An L sugar is the mirror image (enantiomer) of the corresponding D sugar Have an S configuration at the lowest chirality center There are four chiral centers in this molecule and thus 16 possible stereoisomers of which only one occurs naturally.

14.5 Cyclic Structures of Monosaccharides: Hemiacetal Formation Alcohols add reversibly to aldehydes and ketones, forming hemiacetals

Internal Hemiacetals of Sugars Intramolecular nucleophilic addition creates cyclic hemiacetals in sugars Five- and six-membered cyclic hemiacetals are particularly stable Five-membered rings are furanoses. Six-membered are pyanoses Many carbohydrates exist in an equilibrium between open-chain and cyclic forms

Formation cyclic structures Like cyclohexane rings, there are axial and equatorial positions By convention the hemiacetal oxygen is place in the rear of the ring An OH group on the right in a Fischer projection is on the bottom face of the pyranose ring when drawn with the acetal oxygen in the back right. For D sugars the CH2OH group is on the top of the ring.

Formation cyclic structures Note the pyranose and furanose forms depending on which hydroxyl group forms the hemiacetal.

Monosaccharide Anomers: Mutarotation Formation of the cyclic hemiacetal creates an additional chirality center giving two diasteromeric forms, designated  and b These diastereomers are called anomers In the alpha (a) anomer the C1 —OH group is trans to the —CH2OH substituent at C5 In the beta (b) anomer the C1 —OH group is cis to the —CH2OH substituent at C5 a anomer – OH down; b anomer – OH up

Monosaccharide Anomers: Mutarotation Mutarotation refers to the interconversion of alpha and beta isomers. Note the nomenclature indicating these forms for glucopyranose. a anomer – OH down; b anomer – OH up

Monosaccharide Anomers: Mutarotation Mutarotation is reversible Slow at neutral pH Catalyzed by acid and base These forms can be isolated in pure form but in water they interconvert.

14.7 Reactions of Monosaccharides –OH groups can be converted into esters and ethers, which are often easier to work with than the free sugars and are soluble in organic solvents. Esterification by treating with an acid chloride or acid anhydride in the presence of a base All –OH groups react

Ethers Treatment with an alkyl halide in the presence of base—the Williamson ether synthesis Use silver oxide as a catalyst with base-sensitive compounds

Glycoside Formation Treatment of a monosaccharide hemiacetal with an alcohol and an acid catalyst yields an acetal in which the anomeric –OH has been replaced by an –OR group b-D-glucopyranose with methanol and acid gives a mixture of  and b methyl D-glucopyranosides Structures like those on the lower right are called glycosides. Glycosides are stable in water; they are not in equilibrium with an open chain form and thus they do not mutarotate. They can be hydrolyzed back to the hemiacetal on treatment with acid, however. Glycosides are abundant in nature.

Phosphorylation of Monosaccharides In living organisms carbohydrates are often linked through their anomeric center to other biological molecules (called glycoconjugates) Proceeds through a phosphorylation step to activate the anomeric —OH and make it a better leaving group Blood types result from carbohydrates attached to cell surfaces. (polysaccharides)

The Eight Essential Monosaccharides (Continued)

14.9 Disaccharides A disaccharide combines a hydroxyl of one monosaccharide in an acetal linkage with another A glycosidic bond between C1 of the first sugar ( or ) and the –OH at C4 of the second sugar is particularly common (a 1→4 link)

Sucrose “Table Sugar” is pure sucrose, a disaccharide that hydrolyzes to glucose and fructose Connected as an acetal from both anomeric carbons (aldehyde to ketone) Draw maltose with an alpha (down) glycosidic linkage. Leave up on board for two slides.

14.10 Polysaccharides Complex carbohydrates in which very many simple sugars are linked Cellulose and starch are the two most widely occurring polysaccharides

Cellulose Consists of thousands of D-glucopyranosyl 1→4--glucopyranosides as in cellobiose Cellulose molecules form a large aggregate structures held together by hydrogen bonds Cellulose is the main component of wood and plant fiber Cellulose is glucose in beta linkages

Starch and Glycogen Starch is a 1→4--glupyranosyl-glucopyranoside polymer It is digested into glucose There are two components amylose, insoluble in water – 20% of starch 1→4--glycoside polymer amylopectin, soluble in water – 80% of starch

Amylopectin More complex in structure than amylose Has 1→6--glycoside branches approximately every 25 glucose units in addition to 1→4--links Amylopectin differs from amylose in that it has additional branches

Glycogen A polysaccharide that serves the same energy storage function in animals that starch serves in plants Highly branched and larger than amylopectin—up to 100,000 glucose units Starch and glycogen are structurally similar but starch is found in plants and glycogen is found in animals.

14.11 Cell-Surface Carbohydrates and Influenza Viruses Polysaccharides are centrally involved in cell–cell recognition - how one type of cell distinguishes itself from another Small polysaccharide chains, covalently bound by glycosidic links to hydroxyl groups on proteins (glycoproteins), act as biochemical markers on cell surfaces, determining such things as blood type

Let’s Work a Problem The following figure is that of allose. Is this a furanose or pyranose ring form? Is it an a or b anomer? Is it an D or L sugar?

Answer Examination of this structure lets us see that it has a 6-membered ring (pyranose), the C1 OH group is cis to the –CH2OH group (b anomer), and the –O at C5 is on the right side in the uncoiled form (D)