Ch. 8: Carbohydrates

1. 4 major classes of biomolecules Proteins Carbohydrates Fats Nucleic acids Ch. 8: Carbohydrates Ch. 10: Metabolism (intro) Ch. 11: Glycolysis Ch. 12: Other pathyways in carbo. metabolism Diseases associated with sugar metabolism Exam: Tues Mar 2nd

2. Ch. 8: Carbohydrates Most abundant class of macromolecules on the earth Glucose

3. ‘Hydrate of carbon’ Carbohydrate (a.k.a. sugars, saccharide) • (CH2O)n n>3 • Monosaccharide – smallest unit or ‘building blocks’ • Oligosaccharide - disaccharide • Polysaccharide – (more than 20) Glycoconjugates - linked to protein or lipid (2-20) Function Energy storage and release Cell wall and protective coatings Marker mol. on cell surface cell-cell interactions virus invasion… Protein function (covalent modification) DNA/RNA

4. Polyhydroxyl aldehyde (aldose) or Polyhydroxyl ketone (ketose) Aldotriose Glyceraldehyde (D or L) Ketotriose Dyhydroxyacetone D enantiomer predominate in nature Monosaccharides (CH2O)3

5. Monosaccharides - Aldoses # Isomers = 2n where n = # of chiral carbons Enantiomer Distant chiral C From most oxidized Epimers – differ in configuration at only one chiral carbon Not all made in nature

6. Monosaccharides - Ketoses # Isomers = 2n where n = # of chiral carbons

7. Furanose – 5 membered ring, one member O of –OH Pyranose – 6 membered ring, one member O of –OH Cyclization - Ring Structures Optical behavior of monosaccharides in solution suggests that they have an additional chiral center. Similar to:

8. Cyclization of Monosaccharides Most oxidized C New chiral C

9. Cyclization - aldohexose • Draw most oxidized carbon (C1 aldose and C2 ketose) on right and number C clockwise • In ring most oxidizes carbon new chiral center (anomeric C) • Transfer information from Fisher projections • -OH on right then down in Haworth • -OH on left then up in Haworth • Bulky substituent on highest numbered carbon points up Anomers rapid equilibrium

10. Equilibrate in solution In solution at 31°C 64% b-D-glucopyranose 36% a-D-glucopyranose Very little in open chain or furanose form Cyclization - aldohexose Anomers Anomers

11. Cyclization - aldopentose Equilibrium Anomeric C Hemiacetal Haworth projection Anomers

12. “Furanose” Conformations Not planar Rapidly interconvert

13. “Pyranose” Conformations More stable Whether a ring substituent is Equatorial (same plane) or Axial (above/below) depends on whether C-1 or C-4 is above the ring.

14. Important in metabolism Derivatives of monosaccharides – sugar phosphates alcohol phosphate esters Energy metabolism hemiacetal phosphate Nucleic acid metabolism More reactive

15. replacement of one of the -OH groups with H Important in DNA Derivatives of monosaccharides –deoxy sugars

16. RNA DNA OH OH OH OH

17. RNA hydrolysis

18. amino groups or an acetylated amino group replaces one of the -OH groups Derivatives of monosaccharides – amino sugars NeuNAc Sialic acids: on cell surface glycoproteins

19. reduction of carbonyl oxygen, so polyhydroxyl alcohol Derivatives of monosaccharides – sugar alcohols Id glyceraldehyde Idose ---- Inositol

20. derived from aldoses by either the oxidation of C1 or the highest-numbered carbon Glucose oxidation : gluconate or glucuronate gluconate can cyclize under acidic conditions to form a lactone - intramolecular ester. Derivatives of monosaccharides – sugar acids

21. Primates unable to do this reaction Vitamin C or L-Ascorbic Acid

22. Common Carbohydrates and their abbreviations

23. Glycoside Bonds – • acetal linkage between the anomeric carbon of a sugar and an alcohol, an amine, or a thiol • Compounds containing glycoside bonds are called glycosides if glucose donates the anomeric carbon then glucosides

24. Glycoside Bonds – Disaccharides No open chain equil Hemiacetals -a reactive carbonyl that can be oxidized. reducing non-reducing b anomer: refers to free C1 OH (In equilibruim) non-reducing sugar

25. Glycoside Bonds – Disaccharides epimer Most abundant disacc. in nature (plants)

26. Glycoside Bonds – Reducing and Non-reducing • Since mono- and disaccharides are hemiacetals they have a reactive carbonyl that can be oxidized. • Linear polymer usually one reducing end (free anomeric carbon), one non-reducing end, and all internal monosaccharides are acetals that are not in equilibrium with open chains form. • Some polymers such as the disaccharide sucrose do not have a reducing end (both anomeric carbons are involved in the gycosidic bond) so non-reducing sugar.

27. Glycoside Bonds – Other

28. Plant starch – mixture of amylose and amylopectin Animals glycogen Polysaccharides –Glucose Storage • Homoglycans- one type of monosaccharide Amylose • 100-1000 glucose residues (maltose units) Amylopectin and Glycogen Amylopectin: branch every 25 residues Glycogen: branch every 8-12 residues 10% mass of liver • No template (ie no gene)

29. Humans digest starch via two enzymes: α -amylase - endoglycosidase of α-(1-4) linkages (random) debranching enzyme (cleaves limit dextrans) Higher plants have β- amylase exoglycosidase of α- (1-4) linkages, releasing the disaccharide maltose Polysaccharides -Starch Degradation Know how starch is broken down ! Single reducing end

30. Humans don’t have b-glucosidases Microbe that live in ruminants do Polysaccharides –Structure Amylose • Cellulose • b-(1-4) linkage 180 deg rotation 300- 15,000 Glc residues Rigid extended conformation H-bonding Forms bundles or fibrils Plant cell walls, stems and branches termites

31. Chitin found in exoskeletons of insects and crustaceans, and in cell wall of algae and fungi composed of β- (1-4)linkage of GlcNAc residues. Polysaccharides –Structure 2nd most abundant organic compound on earth 180 deg rotation H-bonding Adjacent strands

32. Glycosaminoglycans have dissaccharide components (repeating) one sugar is an amino sugar; e.g. GalNAc, or GlcNAc. The other sugar is usually a uronic acid Certain types can be sulfated, etc. They are highly hydrated, and viscous and are excellent lubricants Glycoconjugates: Proteoglycans unbranched heteroglycan Fluid of joints Elastic and resistant to compression cartilage cartilage

33. Bacteria cell wall, heteroglycans chains linked to peptides GlcNAc linked to N-acetylmuramic acid (MurNAc) joined by β -(1-4) linkage Glycoconjugates: Peptidoglycan Large/rigid mol Defines shape of cell Gram stain +/-

34. O-linked - typically a GalNAc residue linked to the side chain of Ser or Thr, occurs in the golgi N-linked-typically a GlcNAc residue linked to the nitrogen of an Asn, occurs in the endoplasmic reticulum Glycoconjugates - Glycoproteins

35. Glycoconjugates - Glycoproteins N-linked Large amt of structural diversity possible !!

36. Glycoconjugates - Glycoproteins and blood types

37. Draw the Fisher projections of fructose and show how it can cyclize to form both the α and β anomers of fructopyranose and fructofuranose. Draw the disaccharide b-D-ribofuranosyl –(1-4)-a-D-glucopyranose. Is this a reducing or nonreducing sugar? Compare and contrast the structures of starch, glycogen and cellulose. Practice Problems