Carbohydrates Structure and Biological Function Monosaccharides Carbohydrates in Cyclic Structures Reactions of Glucose and Other Monosaccharides Polysaccharides Glycoproteins

Carbohydrates Compounds containing C, H and O General formula : Cx(H2O)y All have C=O and -OH functional groups. Classified based on Size of base carbon chain Number of sugar units Location of C=O Stereochemistry

Types of carbohydrates Classifications based on number of sugar units in total chain. Monosaccharides - single sugar unit Disaccharides - two sugar units Oligosaccharides - 2 to 10 sugar units Polysaccharides - more than 10 units Chaining relies on ‘bridging’ of oxygen atoms glycoside bonds

Monosaccharides Based on location of C=O Aldose Ketose | C=O H-C-OH CH2OH CH2OH | C=O HO-C-H H-C-OH Aldose Ketose - aldehyde C=O - ketone C=O

Monosaccharide classifications Number of carbon atoms in the chain H | C=O H-C-OH CH2OH H | C=O H-C-OH CH2OH H | C=O H-C-OH CH2OH H | C=O H-C-OH CH2OH triose tetrose pentose hexose Can be either aldose or ketose sugar.

Examples D-glyceraldehyde D-fructose triose hexose aldose ketose CH2OH | C=O HO-C-H H-C-OH H | C=O H-C-OH CH2OH D-glyceraldehyde D-fructose triose hexose aldose ketose aldotriose sugar ketohexose sugar

Examples D-ribose L-mannose pentose, aldose hexose, aldose | C=O H-C-OH HO-C-H CH2OH H | C=O H-C-OH CH2OH D-ribose L-mannose pentose, aldose hexose, aldose aldopentose sugar aldohexose sugar

Stereoisomers Stereochemistry Study of the spatial arrangement of molecules. Stereoisomers have the same order and types of bonds. different spatial arrangements. different properties. Many biologically important chemicals, like sugars, exist as stereoisomers. Your body can tell the difference.

Enantiomers Pairs of stereoisomers Designated by D- or L- at the start of the name. They are mirror images that can’t be overlapped. If you don’t believe it, give it a try!

Enantiomers

L- and D- glyceraldehyde

Enantiomers Chiral center. Asymmetric carbon - 4 different things are attached to it. Cl | I - C - F Br You must have at least one asymmetric carbon to have stereoisomers. Chiral center

Examples Is the ‘red’ carbon chiral? C-OH CH2CH3 H3C- H H Cl C=O C=C Br I F H | C=O H-C-OH CH2OH C-OH H H3C- H2N-C-C-C-SH H Cl

Physical properties Optical activity ability to rotate plane polarized light. dextrorotatory - rotate to right - use + symbol - usually D isomers levorotatory - rotate to left - use - symbol - usually L isomers

Plane polarized light Light is passed through a polarized filter. A solution of an optical isomer will rotate the light one direction.

Stereochemistry Properly drawing enantiomers in 3-D is hard. Use Fischer Projections Specific type of formula that designates the orientation of groups. H | C=O H-C-OH CH2OH H | C=O H-C-OH CH2OH

Fischer projections With this system, a tetrahedral carbon atom is represented by two crossed lines. A horizontal bond to an asymmetric carbon designates bonds in the front plane of the page. Vertical bonds are behind the plane of the page. H | C=O H-C-OH CH2OH H O H OH CH2OH

Some important monosaccharides D-glyceraldehyde Simplest sugar D-glucose Most important in diet D-fructose Sweetest of all sugars D-galactose Part of milk sugar D-ribose Used in RNA note that each is a D- enantiomer

D-glyceraldehyde Three carbon sugar Aldose sugar Triose sugar aldotriose H | C=O H-C-OH CH2OH

D-glucose Glucose is an aldohexose sugar. Common names include dextrose, grape sugar, blood sugar. Most important sugar in our diet. Most abundant organic compound found in nature. Level in blood can be as high as 0.1% C CH 2 OH H HO O

D-fructose Another common sugar. It is a ketohexose. Sweetest of all sugars. CH2OH | C=O HO-C-H H-C-OH

Carbohydrates in cyclic structures If optical isomers weren’t enough, sugars also form rings. For many sugars, its the most common form. hemiacetal - forms from alcohol and aldehyde hemiketal - forms from alcohol and ketone R OR’’ \ | C=O + ROH R - C - OH / | R’ R’

Intramolecular cyclization Remember - chains can bend and rotate. C CH2OH OH O H

Intramolecular cyclization The -OH group that forms can be above or below the ring resulting in two forms - anomers  and  are used to identify the two forms.  - OH group is down compared to CH2OH (trans).  - OH group is up compared to CH2OH (cis).

Intramolecular cyclization The  and  forms are in equilibrium so one form can convert to the other - mutarotation. Haworth projections can be used to help see  and  orientations.

Cyclization of D-glucose H OH O CH 2 C HO  - D - glucose

Fischer vs. Haworth projections  -D-glucose H C OH CH OH 2 H C OH H O H H HO C H O H OH H C OH OH OH HO-CH2 C H H OH

Cyclization of D-fructose This can also happen to ketose sugars. CH OH CH2OH 2 O H OH  CH OH 2 H OH C O OH H HO C H H C OH H C OH CH OH OH 2 O CH OH 2 H OH  H CH2OH OH H

D-galactose Not found in many biological systems Common part of lactose - disaccharide CH 2 OH O OH H H O OH H H C H OH H C OH H OH HO C H O OH H CH 2 HO C H H C OH CH 2 OH

D-glucose vs. D-galactose D-glucose D-galactose C CH 2 OH H HO O O C CH 2 OH H HO Can you find a difference? Your body can! You can’t digest galactose - it must be converted to glucose first.

D-ribose An important sugar used in genetic material. This sugar is not used as an energy source but is a part of the backbone of RNA. When the C-2 OH is removed, the sugar becomes deoxyribose which is used in the backbone of DNA. H | C=O H-C-OH CH2OH

Reactions of glucose and other monosaccharides Oxidation-Reduction. Required for their complete metabolic breakdown. Esterification. Production of phosphate esters. Amino derivatives. Used to produce structural components and glycoprotein. Glycoside formation. Linkage of monosaccharides to form polysaccharides.

Oxidation-Reduction. Aldehyde sugars (reducing sugars) are readily oxidized and will react with Benedict’s reagent. This provides a good test for presence of glucose in urine - forms a red precipitate. Other tests - Tollen’s or Fehling’s solutions. H | C=O | + 2 Cu 2+ + 5 OH- H-C-OH CH2OH O- | + 2 Cu2O + 3H2O

Benedict’s reagent B e n d i c t ' s R a g . 5 % 2 l u o

Ketone sugars Ketones are not easy to oxidize except ketoses. Enediol reaction. So all monosaccharides are reducing sugars. C CH 2 OH H HO O CH2OH

Esterification Esters are formed by reaction of hydroxyl groups (alcohols) with acids. The hydroxyl groups of carbohydrates react similarly to alcohols.

D-glucose + ATP D-glucose-6-phosphate + ADP Esterification The most important biological esters of carbohydrates are phosphate esters. Example. Phosphoryl group from ATP forms an ester with D-glucose, catalyzed by kinases. D-glucose + ATP D-glucose-6-phosphate + ADP kinase

Amino derivatives The replacement of a hydroxyl group on a carbohydrate results in an amino sugar. -D-glucose -D-2-aminoglucose (glucosamine)

Amino derivatives Uses for amino sugars. Structural components of bacterial cell walls. As a component of chitin, a polymer found in the exoskeleton of insects and crustaceans. A major structural unit of chondroitin sulfate - a component of cartilage. Component of glycoprotein and glycolipids.

Glycoside formation  or  -OH group of cyclic monosaccharide can form link with another one (or more). glycosidic bond sugar -O- sugar oxygen bridge O H OH CH 2 o + H

Glycosidic bonds  glycosidic bond  glycosidic bond Type is based on the position of the C-1 OH  glycosidic bond - linkage between a C-1  OH and a C-4 OH  glycosidic bond - linkage between a C-1  OH and a C-4 OH  bonds  bonds O O O O C-4 end can be either up or down depending on the orientation of the monosaccharide.

Glycosidic bonds  bonds  bonds O O O O

( ) Glycosidic bonds General format used to describe bond. OH type carbon# of carbon# of ( or ) first sugar second sugar As we work through the next few examples this will become clear. For disaccharides - the sugar is either  or  based on form of the remaining C-1 OH. ( )

-Maltose -D-glucose -D-glucose Malt sugar. Not common in nature except in germinating grains. -D-glucose -D-glucose O H OH CH 2 -D-glucose and -D-glucose,  (1 4) linkage.

-Maltose It is referred to as -maltose because the unreacted C-1 on -D-glucose is in the  position. O H OH CH 2

-Maltose Uses for -maltose Ingredient in infant formulas. Production of beer. Flavoring - fresh baked aroma. It is hydrolyzed the in body by: maltose + H2O 2 glucose maltase

Cellobiose Like maltose, it is composed of two molecules of D-glucose - but with a  (1 4) linkage.

Cellobiose The difference in the linkage results in cellobiose OH CH 2 The difference in the linkage results in cellobiose being unusable We lack an enzyme that can hydrolyze cellobiose. maltose,  (1 4) cellobiose  (1 4)

Lactose -Lactose -D-galactose -D-glucose Milk sugar - dimer of -D-galactose and either the  or  - D-glucose. -Lactose O OH H CH 2 -D-galactose -D-glucose  (1 4) linkage,  disaccharide.

Lactose We can’t directly use galactose. It must be converted to a form of glucose. Galactosemia - absence of needed enzymes needed for conversion. Build up of galactose or a metabolite like dulcitol (galactitol) causes toxic effects. Can lead to retardation, cataracts, death.

Lactose Lactase Enzyme required to hydrolyze lactose. Lactose intolerance Lack or insufficient amount of the enzyme. If lactase enters lower GI, it can cause gas and cramps.

Sucrose (1 2) linkage Table sugar - most common sugar in all plants. Sugar cane and beet, are up to 20% by mass sucrose. Disaccharide of -glucose and -fructose. (1 2) linkage

Sucrose glucose fructose

How sweet it is! Sweetness relative Sugar to sucrose lactose 0.16 galactose 0.32 maltose 0.33 sucrose 1.00 fructose 1.73 aspartame 180 saccharin 450

Polysaccharides Carbohydrate polymers Storage Polysaccharides Energy storage - starch and glycogen Structural Polysaccharides Used to provide protective walls or lubricative coating to cells - cellulose and mucopolysaccharides. Structural Peptidoglycans Bacterial cell walls

Starch Energy storage used by plants Long repeating chain of -D-glucose Chains up to 4000 units Amylose straight chain major form of starch Amylopectin branched structure

Amylose starch Straight chain that forms coils  (1 4) linkage. Most common type of starch. O

Amylose starch Example showing coiled structure - 12 glucose units - hydrogens and side chains are omitted.

Amylopectin starch  (1 6) linkage Branched structure due to crosslinks. OH H O CH 2  (1 6) linkage at crosslink

Glycogen  (1 6) linkage Energy storage of animals. Stored in liver and muscles as granules. Similar to amylopectin.  (1 6) linkage at crosslink O c c

Cellulose Most abundant polysaccharide.  (1 4) glycosidic linkages. Result in long fibers - for plant structure. O H OH CH 2

Mucopolysaccharides These materials provide a thin, viscous, jelly-like coating to cells. The most abundant form is hyaluronic acid. Alternating units of N-acetylglucosamine and D-glucuronic acid. (1 3) (1 4)

Structural peptidoglycans Bacterial cell walls are composed primarily of an unbranched polymer of alternating units of N-acetylglucosamine and N-acetylmuramic acid. Peptide crosslinks between the polymer strands provide extra strength - varies based on bacterium. R = crosslink for Staphylococcus aureus

Glycoproteins Proteins that carry covalently bound carbohydrate units. They have many biological functions. immunological protection cell-cell recognition blood clotting host-pathogen interaction

Glycoprotein structure Carbohydrates only account for 1-30% of the total weight of a glycoprotein. The most common monosaccharides are glucose mannose galactose fucose sialic acid N-acetylgalactosamine N-acetylglucosamine

Glycoprotein structure Linking sugars to proteins. O-glycosidic bonds using hydroxyl groups of serine and threonine N-glycosidic bonds using side chain amide nitrogen of asparagine residue threonine polypeptide chain asparagine