Carbohydrates

1. Carbohydrates

2. Carbohydrates • Most abundant class of biological molecules on Earth • Originally produced through CO2 fixation during photosynthesis

3. Roles of Carbohydrates • Energy storage (glycogen,starch) • Structural components (cellulose,chitin) • Cellular recognition • Carbohydrate derivatives include DNA, RNA, co-factors, glycoproteins, glycolipids

4. Carbohydrates • Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions • Oligosaccharides = "a few" - usually 2 to 10 • Polysaccharides are polymers of the simple sugars

5. Monosaccharides • Polyhydroxy ketones (ketoses) and aldehydes (aldoses) • Aldoses and ketoses contain aldehyde and ketone functions, respectively • Ketose named for “equivalent aldose” + “ul” inserted • Triose, tetrose, etc. denotes number of carbons • Empirical formula = (CH2O)n

6. Monosaccharides are chiral • Aldoses with 3C or more and ketoses with 4C or more are chiral • The number of chiral carbons present in a ketose is always one less than the number found in the same length aldose • Number of possible steroisomers = 2n (n = the number of chiral carbons)

7. Stereochemistry • Enantiomers = mirror images • Pairs of isomers that have opposite configurations at one or more chiral centers but are NOT mirror images are diastereomers • Epimers = Two sugars that differ in configuration at only one chiral center

8. Cyclization of aldose and ketoses introduces additional chiral center • Aldose sugars (glucose) can cyclize to form a cyclic hemiacetal • Ketose sugars (fructose) can cyclize to form a cyclic hemiketal

9. Glucopyranose formation

10. Fructofuranose formation

11. Monosaccharides can cyclize to form Pyranose / Furanose forms a = 64% b = 36% a = 21.5% b = 58.5% a = 13.5% b = 6.5%

12. Haworth Projections -OH up = beta -OH down = alpha 6 5 4 1 2 3 Anomeric carbon (most oxidized) For all non-anomeric carbons, -OH groups point down in Haworth projections if pointing right in Fischer projections

13. Conformation of Monosaccharides Pyranose sugars not planar molecules, prefer to be in either of the two chair conformations.

14. Reducing Sugars • When in the uncyclized form, monosaccharides act as reducing agents. • Free carbonyl group from aldoses or ketoses can reduce Cu2+ and Ag+ ions to insoluble products

15. Derivatives of Monosaccharides

16. Sugar Phosphates

17. Deoxy Acids

18. Amino Sugars

19. Sugar alcohols

20. Monosaccharide structures you need to know • Glucose • Fructose • Ribose • Ribulose • Galactose • Glyceraldehyde

21. Carbohydrates • Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions • Oligosaccharides = "a few" - usually 2 to 10 • Polysaccharides are polymers of the simple sugars

22. Glycosidic Linkage

23. Disaccharides cellobiose maltose (a-D-glucosyl-(1->4)-b-D-glucopyranose) (b-D-glucosyl-(1->4)-b-D-glucopyranose) lactose sucrose (b-D-galactosyl-(1->4)-b-D-glucopyranose) (a-D-glucosyl-(1->2)-b-D-fructofuranose)

24. Higher Oligosaccharides

25. Oligosaccharide groups are incorporated in to many drug structures

26. Polysaccharides • Nomenclature: homopolysaccharide vs. heteropolysaccharide • Starch and glycogen are storage molecules • Chitin and cellulose are structural molecules • Cell surface polysaccharides are recognition molecules

27. Starch • A plant storage polysaccharide • Two forms: amylose and amylopectin • Most starch is 10-30% amylose and 70-90% amylopectin • Average amylose chain length 100 to 1000 residues • Branches in amylopectin every 25 residues (15-25 residues) a-1->6 linkages • Amylose has a-1->4 links, one reducing end

28. Amylose and Amylopectin

29. Starch • Amylose is poorly soluble in water, but forms micellar suspensions • In these suspensions, amylose is helical

30. Glycogen • Storage polysaccharide in animals • Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass • Glycogen is stored energy for the organism • Only difference from starch: number of branches • Alpha(1,6) branches every 8-12 residues • Like amylopectin, glycogen gives a red-violet color with iodine

31. Dextrans • If you change the main linkages between glucose from alpha(1,4) to alpha(1,6), you get a new family of polysaccharides - dextrans • Branches can be (1,2), (1,3), or (1,4) • Dextrans formed by bacteria are components of dental plaque • Cross-linked dextrans are used as "Sephadex" gels in column chromatography • These gels are up to 98% water!

32. Dextrans

33. Cellulose • Cellulose is the most abundant natural polymer on earth • Cellulose is the principal strength and support of trees and plants • Cellulose can also be soft and fuzzy - in cotton

34. Cellulose vs Amylose amylose cellulose Glucose units rotated 180o relative to next residue

35. Cellulose • Beta(1,4) linkages make all the difference! • Strands of cellulose form extended ribbons • Interchain H-bonding allows multi-chain interactions. Forms cable like structures.

36. Chitin • exoskeletons of crustaceans, insects and spiders, and cell walls of fungi • similar to cellulose, but instead of glucose uses N-acetyl glucosamine (C-2s are N-acetyl instead of –OH) • b-1->4 linked N-acetylglucosamine units • cellulose strands are parallel, chitins can be parallell or antiparallel

37. Chitin vs Cellulose

38. Peptidoglycan • N-acetylglucosamine and N-acetylmuramic acid groups linked b-1->4 • Heteroglycan linked to a tetrtapeptide (Ala-IsoGlu-Lys-Ala) • Gram (-) have petanta- glycine linker to next strand • Gram (+) have directly cross links to next strand

39. Peptidoglycan

40. Peptidoglycan is target of antibacterial agents • Lysozyme = enzyme that cleaves polysaccharide chain of peptidoglycan • Penicillin = inhibits linking of peptidoglycan chains. • Inhibits bond formation between terminal alanine and pentaglycine linker • Penicillian looks like an Ala-Ala

41. Peptidoglycan and Bacterial Cell Walls Composed of 1 or 2 bilayers and peptidoglycan shell • Gram-positive: One bilayer and thick peptidoglycan outer shell • Gram-negative: Two bilayers with thin peptidoglycan shell in between • Gram-positive: pentaglycine bridge connects tetrapeptides • Gram-negative: direct amide bond between tetrapeptides

43. Glycoproteins • May be N-linked or O-linked • N-linked saccharides are attached via the amide nitrogens of asparagine residues • O-linked saccharides are attached to hydroxyl groups of serine, threonine or hydroxylysine

45. O-linked Glycoproteins • Function in many cases is to adopt an extended conformation • These extended conformations resemble "bristle brushes" • Bristle brush structure extends functional domains up from membrane surface

46. O-linked Glycoproteins

47. N-linked Glycoproteins • Oligosaccharides can alter the chemical and physical properties of proteins • Oligosaccharides can stabilize protein conformations and/or protect against proteolysis • Cleavage of monosaccharide units from N-linked glycoproteins in blood targets them for degradation in the liver • Involved in targeting proteins to specific subcellular compartments