Chapter 7: Carbohydrates and Glycobiology

1. Chapter 7:Carbohydrates and Glycobiology Dr. Clower Chem 4202

2. Outline, part 1 (sections 7.1-7.2) Types of Carbohydrates Monosaccharides Classification Stereochemistry Structure Chemical Properties Disaccharides Structure Nomenclature Polysaccharides Structural Storage

3. Carbohydrates Most abundant organic compounds in nature A major source of energy from our diet Composed of the elements C, H and O Synthesized from CO2, H2O aka saccharides, which means �sugars� In general, empirical formula (C�H2O)n where n = 3

4. Types of Carbohydrates Monosaccharides Cannot be hydrolyzed to give a smaller carbohydrate Simple carbohydrates Complex carbohydrates: Disaccharides: two monosaccharides Polysaccharides: many monosaccharides

5. Classification of Monosaccharides Monosaccharide Unbranched chain of 3-8 C atoms One is carbonyl; others attached to -OH Aldoses contain an aldehyde group (carbon 1) Ketoses contain a ketone group (carbon 2)  

6. Monosaccharides Classification according to the number of C atoms triose = three carbons tetrose = four carbons pentose = five carbons hexose = six carbons, etc.

7. Classify the following monosaccharides: Learning Check

8. Fischer Projections Used to represent carbohydrates (chiral carbons) Places the most oxidized group at the top (C1) Uses horizontal lines for bonds that come forward Uses vertical lines for bonds that go back

9. D and L Notations By convention, the letter L is assigned to the structure with the �OH on the left The letter D is assigned to the structure with �OH on the right

10. D and L Monosaccharides Stereochemistry determined by the asymmetric center farthest from the carbonyl group Most monosaccharides found in living organisms are D

11. Learning Check Indicate whether each is the D or L isomer: Ribose Threose Fructose

12. Epimers Sugars that differ at only one stereocenter

13. D-Glucose Most common hexose Found in fruits, corn syrup, and honey An aldohexose with the formula C6H12O6 Known as blood sugar in the body Building block for many disaccharides and polysaccharides

14. Blood Glucose Level In the body, glucose has a normal concentration of 70-90 mg/dL Depends on time since last meal (rise after eat; decrease as used or stored) In a glucose tolerance test, blood glucose is measured for several hours after ingesting glucose

15. D-Fructose Ketohexose C6H12O6 Differ from glucose at C1 and C2 (location of carbonyl) The sweetest carbohydrate (2x sucrose) Found in fruit juices and honey Formed from hydrolysis of sucrose Converts to glucose in the body

16. D-Galactose Aldohexose Differ from D-glucose at C4 Not found in the free form in nature Obtained from lactose, a disaccharide (milk products) Important in cellular membranes in CNS

19. Hemiacetal Review What is a hemiacetal? How is a hemiacetal formed? What if the alcohol and carbonyl are attached?

20. Hexose hemiacetals Favor formation of 5- or 6-membered rings Hydroxyl group on C5 reacts with the aldehyde or ketone Haworth perspective formulas Can be written from the Fischer projection C1 drawn on the right (anomeric C) The cyclic structure of a D-isomer has the last CH2OH group located above the ring (C6) �OH groups on the left are drawn up (C3) �OH groups on the right are drawn down (C2, C4)

21. Pyranose Analogous to Pyran

22. The carbonyl carbon is the anomeric carbon Becomes chiral in Hayworth perspective formulas Anomers Isomers which differ in placement of hydroxyl on C1 Slightly different chemical and physical properties ?-anomer -OH on anomeric C on opposite side of ring from �CH2OH down for D-sugars b-anomer -OH on anomeric C on same side of ring as �CH2OH up for D-sugars Anomers

23. ? and ? Anomers for D-Glucose

24. Cyclic Structure of Fructose As a ketohexose, fructose forms a cyclic structure when the �OH on C5 reacts with the ketone on C2 Result is 5-atom ring Anomeric carbon is C2 A furanose: analogous to furan

25. Pyranoses and Furanoses

26. Mutarotation In solution, anomers interconvert (slowly) Mutarotation involves the conversion of the cyclic anomers into the open chain At any time, there is only a small amount of linear saccharide

27. Stability of Anomer Conformations Pyranose rings are not planar The most stable chair conformation will dominate

28. Write the cyclic form of ?-D-galactose: Learning Check

29. Sugar Derivatives Formed from reactions of sugar Carbonyl linear form Hydroxyl groups Linear or ring, depending on reaction Some common derivatives: Oxidation of 1� alcohol of aldose Formation of uronic acids (uronate) Deoxy sugars: replace �OH with �H Amino sugars: replace �OH with �NH2 Can be acylated (-NH-C(O)-CH3)

30. Some Hexose Derivatives

31. Review:Reactions of aldehydes Oxidation to form carboxylic acids Reduction to form alcohols Formation of hemiacetal Hemiacetal + alcohol ? acetal

32. Other common derivatives Oxidation of aldehyde of aldose Aldonic acids Reduction of carbonyl of aldose or ketose Alditols Condensation reactions between anomeric �OH and alcohols to form acetals or ketals Glycosides

33. Oxidation of Monosaccharides Aldose ? aldonic acid

34. Reducing Sugars Reducing sugars Free anomeric carbon Benedict�s test Carbonyl group oxidized to give carboxylic acid Copper ion is reduced

35. Reduction of Monosaccharides The reduction of the carbonyl group produces sugar alcohols, or alditols D-Glucose is reduced to D-glucitol (also called sorbitol)

36. Learning Check Write the products of the oxidation and reduction of D-mannose.

37. Glycosides and Glycosidic Bonds When a cyclic monosaccharide reacts with an alcohol: A glycoside is produced (acetal) The bond is a glycosidic bond (a or b) ?-D-Glucose Methanol Methyl-?-D-glucoside

38. Polysaccharides aka glycans Complex carbohydrates Monosaccharides linked by glycosidic bonds Can be branched (unlike polypeptides) Homopolysaccharides One type of monosaccharide Heteropolysaccharides > 1 type of monosaccharide Repetitive sequence Structure determined by hydrolysis (glycosidase) and NMR

39. Disaccharides Simplest polysaccharide Consists of two monosaccharides Disaccharide Monosaccharides Maltose + H2O Glucose + Glucose Lactose + H2O Glucose + Galactose Sucrose + H2O Glucose + Fructose

40. Maltose Malt sugar A disaccharide in which two D-glucose molecules are joined by an ?-1,4-glycosidic bond Obtained from starch Used in cereals, candies, and brewing A reducing sugar

41. Naming Disaccharides Non-reducing end on the left Give configuration (a or b) at anomeric carbon joining residues Name non-reducing residue Add furano or pyrano Glycosidic bond in parenthesis (# ? #) Name second residue

42. Lactose and Sucrose Lactose Milk sugar Galactose and glucose ?-1,4-glycosidic bond Lactose intolerance A reducing sugar Sucrose Table sugar Glucose and fructose ?,?-1,2-glycosidic bond Has no isomers mutarotation is blocked Not a reducing sugar

44. Sweetness of Sweeteners Sugars and artificial sweeteners differ in sweetness Each sweetener is compared to sucrose (table sugar), which is assigned a value of 100 Aspartame Components? Danger to phenylketonurics

45. Polysaccharides Polymers of D-glucose Structural: Cellulose Chitin Storage Starch (Amylose and Amylopectin) Glycogen Glucosaminoglycans

46. Cellulose Plant cell walls Linear polymer Up to 15000 Glc residues ?-1?4 glycosidic bonds Exceptionally strong fiber Water insoluble (no room for water to H-bond) Hydrolyzed by cellulases (slowly) Found in herbivores, termites, wood fungi

47. Cellulose Structure Parallel extended chains Intrachain H-bonds Sheets stack vertically

48. Chitin Same as cellulose, except �OH on C2 replaced with acetamide Amino sugar Homopolymer of N-acetyl-D-glucosamine Very strong Structural component of exoskeleton of arthropods

49. Starch Main carb in human diet Primary source of energy in many foods Composed of amylose (20%) and amylopectin (80%) Amylose Continuous chain linked by ?-1,4 glycosidic bonds Forms left-handed helix Amylopectin Branched chain (~ every 25 residues) linked by ?-1,4- and ?-1,6-glycosidic bonds

50. Glycogen Same function (as starch) in animals Similar to amylopectin, but more highly branched

51. Hydrolysis of polysaccharides Mashed potatoes or mashed paper? Enzymes in saliva and stomach (amylase, a glycosidase) can hydrolyze ?-1,4 glycosidic bonds in starch, but not ?-1,4 glycosidic bonds in cellulose

52. Folding of Polysaccharides Maximize H-bonding, minimize steric strain

53. Glycosaminoglycans Gel-like matrix surrounding collagen in cartilage, tendons, skin Unbranched polysaccharides High elasticity and viscosity Alternating uronic acid and hexosamine Frequently contain sulfate groups

54. Glycosaminoglycans

55. Summary of Polysaccharides

56. Outline, part 2 (sections 7.3, 7.5) Glycoconjugates Glycolipids Glycoproteins Proteoglycans Peptidoglycans Determination of carbohydrate structure

57. Glycoconjugates Covalent bond between carbohydrate and biomolecule Glycoproteins Glycolipids Function of oilgosaccharides: Structural Hydrophilic (protein surface) Limit conformations Reactivity Shield surface and affect reactivity Surface Recognition Label proteins Intracellular communication

58. Glycolipids Membrane lipids Hydrophilic heads are oligosaccharides Recognition sites

59. Glycoproteins Proteins with carbohydrates Microheterogeneity Variable composition Range from 1-90% Large array of functions Structure, transport, enzymes, receptors, etc. Carbohydrate chains Often short (oligosaccharide) May be branched Synthesized by enzymatic reaction Covalently linked to polypeptide

60. Proteoglycans Extracellular aggregate of protein and glycosaminoglycans Core protein Oligosaccharide glycosidic bond to O of Ser or Thr

61. Proteoglycan Aggregates Backbone 4000-40000 � Single hyalurnoate molecule Core proteins Up to 100 Many types Oligosaccharides N-linked O-linked Sulfonated Highly hydrated Anionic Extended structure High resilience

62. N- and O-linkages

63. Peptidoglycan Bacterial cell walls Covalently linked polysaccharide and polypeptide chains D-AAs resist hydrolysis by peptidases Lysozyme can break down cell wall Penicillins can prohibit synthesis (cross-linking)

64. Determination of Structure

65. Chapter 7 Problems 2-5, 8-11, 13-17