Carbohydrates Learning Objectives What Are the Structures and the Stereochemistry of Monosaccharides? How Do Monosaccharides React? What are Disaccharides ? What Are Some Important Oligosaccharides? What Are the Structures and Functions of Polysaccharides? What Are Glycoproteins?

Carbohydrates Carbohydrate: a polyhydroxyaldehyde or polyhydroxyketone, or a substance that contain C:H:O and H:O ratio is 2:1 (as water) ~ose designate sugars. Monosaccharide: a carbohydrate that cannot be hydrolyzed to a simpler carbohydrate they have the general formula CnH2nOn, where n varies from 3 to 8 Monosaccharide maybe aldose: a monosaccharide containing an aldehyde group ketose: a monosaccharide containing a ketone group

Monosaccharides Monosaccharides are classified by their number of carbon atoms

Fischer Projections Fischer projection: a two dimensional representation for showing the configuration of tetrahedral horizontal lines represent bonds projecting forward vertical lines represent bonds projecting to the rear

Monosaccharides There are only two trioses aldo- and keto- are often omitted and these compounds are referred to simply as trioses; although this designation does not tell the nature of the carbonyl group, it at least tells the number of carbons D ihydroxyacetone (a ketotriose) Glyceraldehyde (an aldotriose) C H O 2 =

D- Aldoses

D-Ketoses

Hexoses of physiologic importance. Sugar Source Importance Clinical Significance D-Glucose Fruit juices. Hydrolysis of starch, cane sugar, maltose, and lactose. The sugar of the body. carried by blood the principal one used by the tissues Present in the urine (glucosuria) in diabetes mellitus owing to raised blood glucose (hyperglycemia) D-Fructose Fruit juices. Honey. Hydrolysis of cane sugar and of inulin. Can be changed to glucose in the liver Hereditary fructose intolerance leads to fructose accumulation and hypoglycemia.

Hexoses of physiologic importance. Sugar Source Importance Clinical Significance D-Galactose Hydrolysis of lactose. Can be changed to glucose in the liver and metabolized. Synthesized in the mammary gland to make the lactose of milk. A constituent of glycolipids and glycoproteins. Failure to metabolize leads to galactosemia and cataract. D-Mannose Hydrolysis of plant mannans and gums. A constituent of many glycoproteins.

Sucralose ( Splenda ) Discovered in 1976, sucralose is 600 times sweeter than sugar and does not metabolize to produce energy, thus it does not contain calories. It is the only low calorie sweetener that is made from sugar, which has been changed so passes through the body unchanged and unmetabolized. Substituting for three alcohol groups on the sugar molecule with 3 chlorine atoms.

Stevia Stevia is a sweetener and sugar substitute extracted from the leaves of the plant species Stevia rebaudiana which is grown in Brazil and Paraguay. Stevia has no calories, and it is 200 times sweeter than sugar in the same concentration.

Monosaccharides Glyceraldehyde contains a stereocenter (chiral C) and exists as a pair of stereoisomers (enantiomers) Note: Number of stereoisomers= 2n n is the number of stereocenters (chiral carbon)

D, L Monosaccharides According to the conventions proposed by Fischer D-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH on its penultimate carbon (the one before the last= the highest numbered chiral carbon) on the right L-monosaccharide: a monosaccharide that, when written as a Fischer projection, has the -OH on its penultimate carbon (the one before the last= the highest numbered chiral carbon) on the left

The four aldotetroses Enantiomers: stereoisomers that are mirror images . example: D-erythrose and L-erythrose are enantiomers Diastereomers: stereoisomers that are not mirror images . Epimers: diastereomers that differ from each other in configuration of one chiral carbon example: D-erythrose and D-threose are diastereomers

D, L Monosaccharides Following are the two most common D-aldotetroses and the two most common D-aldopentoses

C H O D-Glucosamine D-Glucose D-Galactose N D-Fructose The three most common D-aldohexoses. Note that the third of these is an amino sugar. also shown is the most common 2-keto-D-hexose C H O 2 D-Glucosamine D-Glucose D-Galactose N D-Fructose

Cyclic Structure Monosaccharides especially pentoses and hexoses have -OH and C=O groups in the same molecule and exist almost entirely as five- and six-membered cyclic hemiacetals or hemiketal Hemiacetal : bond between C=O on C1 (aldehyde) and -OH on last chiral C Hemiketal: bond between C=O on C2 (ketone) and -OH on last chiral C Cyclic strusture will display extra chiral carbon (anomeric carbon) anomeric carbon: the new stereocenter resulting from cyclic hemiacetal or hemiketal formation anomers: monosaccharides that differ in configuration only at their anomeric carbons

Haworth Projections Haworth projections five- and six-membered hemiacetals are represented as planar pentagons or hexagons most commonly written with the anomeric carbon on the right and the hemiacetal oxygen to the back right the designation -means that -OH on the anomeric carbon is cis to the terminal -CH2OH (above the plane); - means that it is trans to the terminal -CH2OH (below the plane) The OH groups on the right in Fischer below in Haworth. Those to the left in Fischer upward in Haworth. Counting is clockwise starting from anomeric carbon

Haworth Projections

Haworth Projections a six-membered hemiacetal ring is shown by the infix -pyran- a five-membered hemiacetal ring is shown by the infix -furan- Pyranose: a six-membered ring sugar Furanose: a five-membered ring sugar

Haworth Projections Five-membered rings are so close to being planar that Haworth projections are adequate to represent furanoses.

Comparison of the Fischer and Haworth Representations

Comparison of the Fischer and Haworth Representations

Oxidation Reducing sugar: one that reduces an oxidizing agent Reducing sugar: has free aldehyde or ketone group oxidation of a cyclic hemiacetal form gives a lactone when the oxidizing agent is Tollens’ reagent (used to detect reducing sugars), Ag precipitates as a silver mirror

Ascorbic Acid (Vitamin C) L-Ascorbic acid (vitamin C) is synthesized both biochemically and industrially from oxidation of D-glucose

Ascorbic Acid (Vitamin C) L-Ascorbic acid is very easily oxidized to L-dehydroascorbic acid both are physiologically active and are found in most body fluids

Reduction The carbonyl group of a monosaccharide can be reduced to a hydroxyl group by a variety of reducing agents reduction of the CHO group of a monosaccharide gives a polyhydroxy compound called an alditol Commercial sweetener in sugarless gum and candy

Reduction Reactions

Formation of deoxy sugars B-L-Fucose in ABO blood group antigens, polypeptide chain D-2-deoxyribose in DNA

Phosphoric Esters Phosphoric esters are particularly important in the metabolism of sugars phosphoric esters are frequently formed by transfer of a phosphate group from ATP H O C 2 b -D-glucose - P A d e n o s i + ATP 3 -D-glucose-6-phosphate D enzyme

Formation of Glycosides Glycoside: a carbohydrate in which the -OH of the anomeric carbon is replaced by -OR those derived from furanoses are furanosides; those derived from pyranoses are pyranosides O-glycosidic bond: the bond in the glycoside, between the anomeric carbon and the -OR group (methyl alcohol)

Amino Sugars The bond involved is N-glycosidic bond

Glycosidic linkages Glycosidic linkages can take various forms; the anomeric carbon of one sugar to any of the -OH groups of another sugar to forma an - or -glycosidic linkage

Disaccharides Sucrose table sugar; obtained from the juice of sugar cane and sugar beet one unit of D-glucose and one unit of D-fructose joined by an a-1,2-glycosidic bond nonreducing sugar: no reducing ends

Disaccharides Lactose about 5% - 8% in human milk, 4% - 5% in cow’s milk one unit of D-galactose and one unit of D-glucose joined by a b-1,4-glycosidic bond reducing sugar: has reducing ends Lactose intolerance

Disaccharides Maltose two units of D-glucose joined by an a-1,4-glycosidic bond Resulted from hydrolysis of starch reducing sugar: has reducing ends

Disaccharides Cellobiose Two units of β-glucose linked by β-(1-4) glycosidic bond

Reducing disaccharides

Polysaccharides Cellulose: the major structural component of plants, especially wood and plant fibers a linear polymer of approximately 2800 D-glucose units per molecule joined by b-1,4-glycosidic bonds fully extended conformation with alternating 180° flips of glucose units extensive intra- and intermolecular hydrogen bonding between chains

Starch A polymers of a-D-glucose units and used for energy storage in plants, 2 forms amylose: continuous, helical unbranched chains of up to 4000 a-D-glucose units joined by -1,4-glycosidic bonds amylopectin: a highly branched helical polymer consisting of 24-30 units of D-glucose joined by _1,4-glycosidic bonds and branches created by -1,6-glycosidic bonds amylases catalyze hydrolysis of -1,4-glycosidic bonds debranching enzymes catalyze the hydrolysis of

Starch

Polysaccharides Branching in amylopectin and glycogen The difference between amylopectin and glycogen is no. of branches Glycogen every 10 Amylopectin every 25

Polysaccharides Chitin: the major structural component of the exoskeletons of invertebrates, such as insects and crustaceans; also occurs in cell walls of algae, fungi, and yeasts composed of units of N-acetyl--D-glucosamine joined by -1,4-glycosidic bonds

Polysaccharides Bacterial cell walls: prokaryotic cell walls are constructed on the framework of the repeating unit NAM-NAG joined by b-1,4-glycosidic bonds

Bacterial Cell Walls The N-acetyl-D-glucoseamine and N-acetylmuramic acid polysaccharide is in turn cross-linked by small peptides in Staphylococcus aureus, the cross link is a tetrapeptide this tetrapeptide is unusual in that it contains two amino acids of the D-series, namely D-Ala and D-Gln each tetrapeptide is cross linked to an adjacent tetrapeptide by a pentapeptide of five glycine units Peptidoglycan: is the resulted cross linking of polysaccharides by peptides

Bacterial Cell Walls

Bacterial Cell Walls The peptidoglycan of a bacterial cell wall Staphylococcus aureus

Polysaccharides Glycosaminoglycans: polysaccharides based on a repeating disaccharide where one of the monomers is an amino sugar and the other has a negative charge due to acid such as a sulfate or carboxylate group heparin: natural anticoagulant hyaluronic acid: a component of the vitreous humor of the eye and the lubricating fluid of joints chondroitin sulfate and keratan sulfate: components of connective tissue

The repeating unit of heparin

The repeating unit of hyaluronic acid

Chondroitin sulfate The repeating unit of chondroitin sulfate

Glycoproteins antibodies are glycoproteins Glycoproteins contain carbohydrate units covalently bonded to a polypeptide chain antibodies are glycoproteins carbohydrates play a role as antigenic determinants, the portions of the antigenic molecule that antibodies recognize and to which they bond.

Blood Group Substances Membranes of animal plasma cells have large numbers of relatively small carbohydrates bound to them: these membrane-bound carbohydrates act as antigenic determinants among the first antigenic determinants discovered were the blood group substances in the ABO system, individuals are classified according to four blood types: A, B, AB, and O at the cellular level, the biochemical basis for this classification is a group of relatively small membrane-bound carbohydrates

ABO Blood Classification

ABO Blood Classification in type A, the nonreducing end is NAGal in type B it is Gal in type AB, both types are present in Type O, neither of these terminal residues is present

End Chapter 16