HL Chemistry - Option B: Human Biochemistry

1. HL Chemistry - Option B: Human Biochemistry Carbohydrates “The Discovery of Honey” by Piero de Cosimo (1462)

2. Part 1 Overview of Carbohydrates

3. General Characteristics • The term carbohydrate is derived from the French: “hydrate de carbone” • All carbohydrates are compounds composed of (at least) C, H, and O • The general formula for a carbohydrate is: (CH2O)n (e.g. when n = 5 then the formula would be C5H10O5) • Not all carbohydrates have this empirical formula (e.g. deoxysugars, aminosugars, etc.) • Carbohydrates are the most abundant compounds found in nature (e.g. cellulose: 100 billion tons annually)

4. General Characteristics • In nature, most carbohydrates are found bound to other compounds rather than as simple sugars • Polysaccharides (starch, cellulose, inulin, gums) • Glycoproteins and proteoglycans (hormones, blood group substances, antibodies) • Glycolipids (cerebrosides, gangliosides) • Glycosides • Mucopolysaccharides (hyaluronic acid) • Nucleic acid polymers

5. Carbohydrate Functions Carbohydrates can be: • Sources of energy • Intermediates in the biosynthesis of other basic biochemical entities (fats and proteins) • Associated with other entities such as glycosides, vitamins and antibiotics) • Structural tissues in plants and in microorganisms (cellulose, lignin, murein) • Involved in biological transport, cell-cell recognition, activation of growth factors, modulation of the immune system

6. Classification of Carbohydrates Carbohydrates can be classified by size: • Monosaccharides (monoses or glycoses) • Trioses, tetroses, pentoses, hexoses • Oligosaccharides • Di, tri, tetra, penta …up to 10 • (The disaccharides are the most important) • Polysaccharides (or glycans) • Homopolysaccharides (all the same type) • Heteropolysaccharides (mixtures of momomer types) • Complex carbohydrates (joined to non-carbohydrate molecules)

7. Monosaccharides • Monosaccharides are also known as “simple sugars” • They are classified by (1) the number of carbons and (2) whether they are aldoses or ketoses (more to come on this!) • Most (99%) simple sugars are straight chain compounds • D-glyceraldehyde is the simplest of the aldoses (aldotriose) • All other sugars have the ending ose(glucose, galactose, ribose, lactose, etc…)

8. Monosaccharides Aldoses (e.g. glucose) have an aldo (aldehyde) group at one end Ketoses (e.g. fructose) have a keto (ketone) group (usually at C2)

9. Aldose sugars

10. Ketose sugars

11. D- vs L- Designation D & L designations are based on the configuration about the single asymmetric C in glyceraldehyde The lower diagrams are Fischer Projections.

12. Sugar Nomenclature For sugars with more than one chiral center, D or Lrefers to the asymmetric C farthest from the aldehyde or keto group (in yellow) Most naturally occurring sugars are D isomers

13. D & L sugars are mirror images of one another They have the same root name (but a different D/L designation), [e.g. D-glucose & L-glucose] Other stereoisomers have unique names, (e.g. glucose, mannose, galactose, etc) The number of stereoisomers is 2n, where n is the number of asymmetric (chiral) centers The 6-C aldoses have 4 asymmetric centers. Thus there are 16 stereoisomers (8 D-sugars and 8 L-sugars).

14. Structure of a Simple Aldose and a Simple Ketose

15. Enantiomers and Epimers

16. Relationship Between D- & L-Fructose

17. Properties of Optical Isomers • The differences in structures (configurations) of sugar optical isomers are responsible for variations in properties • Physical Differences Between D- & L- forms • Crystalline structure; solubility; rotatory power • Chemical Differences Between D- & L- forms • Reactions (oxidations, reductions, condensations) • Physiological Differences Between D- & L- forms • Nutritive value (human, bacterial); sweetness; absorption

20. Structural Representation of Sugars Biomolecules (in this case sugars) can be represented in three main ways (visualized in the following slides): • Fischer Projection: straight chain representation • Haworth Projection: simple ring in perspective • Conformational Representation: chair and boat configurations

21. Pentoses and hexoses can cyclize as the ketone or aldehyde reacts with a distal OH. The top diagram is a Fischer Projection of D-Glucose Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde & C5 OH react, to form a 6-member pyranose ring, named after pyran The representations of the cyclic sugars (bottom) are called Haworth Projections

22. More Pyran Cyclization

23. Fructose forms either a: • 6-member pyranose ring: reaction of the C2 keto group with the OH on C6, or • 5-member furanose ring: reaction of the C2 keto group with the OH on C5

24. Cyclization of glucose produces a new asymmetriccenter at C1. The 2 stereoisomers are called anomers, a &b Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1: • a(OH below the ring) • b (OH above the ring)

25. Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar The representation above reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection

26. Chair (top) and Boat (bottom) forms of the Pyranose Ring

27. Optical Isomerism and Polarimetry • Recall that optical isomerism is a property exhibited by any compound whose mirror images are non-superimposable • Also, compounds with asymmetric carbons rotate plane polarized light – • Measurement of optical activity in chiral or asymmetric molecules uses plane polarized light • Molecules may be chiral because of certain atoms or because of chiral axes or chiral planes • Measurement uses an instrument called a polarimeter (Lippich type) • Rotation is either (+) dextrorotatory or (-) levorotatory

28. Polarimeter

29. Polarimetry Selected Rotations D-glucose +52.7 D-fructose -92.4 D-galactose +80.2 L-arabinose +104.5 D-mannose +14.2 D-arabinose -105.0 D-xylose +18.8 Lactose +55.4 Sucrose +66.5 Maltose+ +130.4 Invert sugar -19.8 Dextrin +195 • Magnitude of rotation depends upon: 1. The nature of the compound 2. The length of the tube (cell or sample container) usually expressed in decimeters (dm) 3. The wavelength of the light source employed; usually either sodium D line at 589.3 nm or mercury vapor lamp at 546.1 nm 4. Temperature of sample 5. Concentration of carbohydrate in grams per 100 ml

30. Part 2 Oligosaccharides and selected derivatives

31. Oligosaccharides • The most common oligosaccarides are the disaccharides • Sucrose, lactose, and maltose • Maltose hydrolyzes to 2 molecules of D-glucose • Lactose hydrolyzes to a molecule of glucose and a molecule of galactose • Sucrose hydrolyzes to a molecule of glucose and a molecule of fructose

32. Glycosidic Bonds The anomeric hydroxyl and a hydroxyl of another sugar or some other compound can join together, splitting out water to form a glycosidic bond: R-OH+ HO-R'R-O-R' + H2O e.g. methanol reacts with the anomeric OH on glucose to form methyl glucoside (methyl-glucopyranose).

33. Disaccharides: Maltose, a cleavage product of starch (i.e. amylose), is a disaccharide with an a(1®4) glycosidiclink between the C1 - C4 OH’s of 2 glucoses. It is the a anomer (C1 O points down) Cellobiose, a product of cellulose breakdown, is the otherwise equivalent banomer (O on C1 points up). The b(1®4) glycosidic linkage is represented as a zig-zag, but one glucose is actually flipped over relative to the other

34. Other disaccharides include: • Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose & fructose. Because the configuration at the anomeric C of glucose is a (O points down from ring), the linkage is a(12) The full name of sucrose is a-D-glucopyranosyl-(12)-b-D-fructopyranose.) • Lactose, milk sugar, is composed of galactose& glucose, with b(14) linkage from the anomeric OH of galactose. Its full name is b-D-galactopyranosyl-(14)-a-D-glucopyranose

35. Sucrose • Probably the most famous sugar, and everyone’s favorite, is sucrose: • a-D-glucopyranosido-b-D-fructofuranoside • b-D-fructofuranosido-a-D-glucopyranoside • Also known as table sugar • Commercially obtained from sugar cane or sugar beet • Hydrolysis yield glucose and fructose (invert sugar) ( sucrose: +66.5o ; glucose +52.5o; fructose –92o) • Used pharmaceutically to make syrups

36. Lactose • Lactose is another famous disaccharide, resulting from b-D-galactose joining to a-D-glucose via a b-(1,4) linkage • Milk contains the a and b-anomers in a 2:3 ratio • b-lactose is sweeter and more soluble than ordinary a- lactose • Used in infant formulations, medium for penicillin production and as a diluent in pharmaceuticals

37. Starch • Starch is the most common storage polysaccharide in plants • It is composed of 10 – 30% a-amylose and 70-90% amylopectin (depending on the source) • The chains are of varying length, having molecular weights from several thousands to half a million

38. Polysaccharides • Plants store glucose as amylose or amylopectin. Glucose polymers collectively are called starch. Glucose storage in polymeric form minimizes osmotic effects. • Amylose is a glucose polymer with a(14) linkages. It adopts a helical conformation (see above) • The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the reducing end

39. Amylopectin is a glucose polymer with mainly a(14) linkages, but it also has branches formed by a(16) linkages (see above). Branches are generally longer than shown above. • The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur.

40. Another view of amylose and amylopectin, the two forms of starch. Amylopectin is a highly branched structure, with branches occurring every 12 to 30 residues

41. Glycogen • Glycogen is also known as “animal starch” (not really an accurate description!) • It is stored in muscle and liver tissue • Also present in cells as granules (high MW) • It contains both a-(1,4) links and a-(1,6) branches at every 8 to 12 glucose unit • Complete hydrolysis yields glucose • Glycogen and iodine gives a red-violet color • Hydrolyzed by both a and b-amylases and by glycogen phosphorylase [these are enymes]

42. Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin, but glycogen has more a(16)branches • The highly branched structure permits rapid release of glucose from glycogen stores, i.e. in muscle during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants

43. Cellulose • Cellulose is a polymer of b-D-glucose attached by b-(1,4) linkages • It yields glucose upon complete hydrolysis • Partial hydrolysis yields cellulobiose • Cellulose is the most abundant of all carbohydrates • Cotton flax: 97-99% cellulose • Wood: ~ 50% cellulose • Cellulose gives no color with iodine • Held together with “lignin” in woody plant tissues

44. Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose with b(1®4) linkages. • Every other glucose is flipped over, due to the b linkages. This promotes intra-chain and inter-chain H-bonds and van der Waals interactions. This cause cellulose chains to be straight & rigid, and pack with a crystalline arrangement in thick bundles called microfibrils

45. The Linear Structures of Cellulose and Chitin (chitin is found in the exoskeleton of insects, crayfish, etc] (these are the two most abundant polysaccharides in nature)

46. The Molecular Structure of Cellulose (Notice the presence of “sheets” that can be pealed away. Think about a piece of celery and how you can strip off the fibers)

47. Suspensions of amylose in water adopt a helical conformation Iodine (I2) can insert in the middle of the amylose helix to give a blue color that is characteristic and diagnostic for starch

48. (a) The structure of starch – shows a linkages (b) The structure of cellulose– shows b linkages

49. Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains O-linked oligosaccharidechains of glycoproteins vary in complexity. • They link to a protein via a glycosidic bond between a sugar residue and a serine or threonine OH • O-linked oligosaccharides have roles in recognition, interaction, and enzyme regulation

50. The Structures of Serine or Threonine O-linked Saccharides