CARBOHYDRATE STRUCTURE AND FUNCTION pt -1

1. CARBOHYDRATE STRUCTURE AND FUNCTIONpt -1 Dr. Deon Bennett 2012

2. CARBOHYDRATE STRUCTURE • CARBOHYDRATES are the single most abundant class of organic molecules found in nature. • The name CARBOHYDRATE arises from the basic molecular formula (CH2O)n or (CH2O)nhydrates of carbon where n = 3 or more. • CARBOHYDRATES constitute a versatile class of molecules. • Energy from the sun captured by green plants, algae and some bacteria during photosynthesis is stored in the form of carbohydrates.

3. CARBOHYDRATE STRUCTURE • CARBOHYDRATES are the metabolic precursors of virtually all other biomolecules. Breakdown of carbohydrates provides the energy that sustains animal life. • CARBOHYDRATES are linked to other molecules: • Lipids to form glycolipids …….biological membranes • Proteins to form glycoproteins ……..cell walls These GLYCOCONJUGATES are important components of cell walls, extracellular structures and recognition between cell types.

4. Carbohydrates • Serves as energy stores, fuels and metabolic intermediates. • Forms part of the structural framework of RNA and DNA. • Polysaccharides are structural elements in cell walls of bacteria and plants.

5. CHEMICAL FEATURES OF CARBOHYDRATES • The existence of at least one and often two or more ASYMMETRIC centers. • The ability to exist either in LINEAR or RING structures. • The capacity to form polyhydric structures via GLYCOSIDIC bonds. • The potential to form multiple hydrogen bonds with water or other molecules in their environment.

6. Carbohydrates are divided into four major classes: • Monosaccharides or simple sugars • Oligosaccharides – composed of several of the same or different monosaccharides • Polysaccharides – composed of many monosaccharide units • Homopolysaccharides – eg starch • Heteropolysaccharides – eg peptidoglycan • Mucopolysaccharides – egchondroitin sulphate • Carbohydrate derivatives or Miscellaneous compounds

7. CARBOHYDRATE NOMENCLATURE Carbohydrates are generally classified into three groups: • Class(DP)1 Subgroup Components Monosaccharide Glucose, galactose, fructose Sugars Disaccharides Sucrose, lactose, maltose Polyols Sorbitol, mannitol

8. CARBOHYDRATE NOMENCLATURE Malto-Oligosaccharide Maltodextrins Oligosaccharide Other oligosaccharides Raffinose, starchyose, fructo- oligosaccharide Polysaccharides Starch Amylose, amylopectin, modified starches Non starch Cellulose, hemicellulose polysaccharide Pectins, hydrocolloids

9. Monosaccharide • Most taste sweet. Contain 3-7 carbon atoms. • Are either an aldose or a ketose • Aldoses contain an aldehyde functional group • Ketoses contain a ketone functional group

10. Physical Properties of Monosaccharides • They are all sweet tasting, but their relative sweetness varies a great deal. • They are polar compounds with high melting points. • The presence of so many polar functional groups capable of hydrogen bonding makes them water soluble. • Unlike most other organic compounds, monosaccharides are so polar that they are insoluble in organic solvents like diethyl ether.

11. Monosaccharide

12. Classification of monosaccharides: Monosaccharides are classified according to the number of C-atoms in the molecule. They are further divided into “aldo-sugar” or “keto-sugar” depending on whether they carry an aldehydic or ketonic group: • TRIOSES – those containing 3 C-atoms • TETROSES – those containing 4 C-atoms • PENTOSES – “ 5 C-atoms • HEXOSES – “ 6 C-atoms • HEPTOSES – “ 7 C-atoms

13. Classification of Monosaccharides cont’d: • TRIOSES: Aldo-triose (D-Glyceraldehyde) & Keto-triose (Dihydroxyacetone) • TETROSES: Aldo-tetroses (egs. D-Erythrose, D-Threose) • & Keto-tetroses (eg. D-Erythrulose) • PENTOSES: Aldo-pentoses (egs. D-Ribose, D-Arabinose, D-Xylose, D-Lyxose) • & Keto-pentoses (egs. D-Ribulose, D-Xylulose) • HEXOSES: Aldo-hexoses (egs. D-Glucose, D-Mannose, D-Galactose, etc.). • & Keto-hexoses (egs.D-Fructose, D-Sorbose, D-Tagatose, etc) • HEPTOSES: Keto-heptose (Sedoheptulose) • Note: • Some of these Ketoses are named by the insertion of “ul” before the suffix “ose” in the name of the corresponding aldose eg. D-Xylulose is the Keto form corresponding to D-Xylose. • Glucose is the most predominant sugar! It is the only aldose that commonly occurs in nature as a monosaccharide.

14. The Family of D-Aldoses

15. The Family of D-Ketoses

16. Stereochemistry • In addition to the general name of the monosaccharide, the stereochemistry about each chiral center is important. • We need a convenient way to represent such stereochemical features when drawing monosaccharides. • The solution to these problems is the Fischer projection method of drawing such molecules.

17. Fischer Projection • The carbonyl group of the keto or aldose functional group is considered to be closest to the "start" of the carbon chain. • The carbon thus identified as the "first" carbon in the chain is carbon #1. • The remaining carbons are numbered sequentially. • The "highest numbered" asymmetric carbon (i.e. furthest from the "start" carbon) determines whether the monosaccharide is the "D" or "L" isomer.

18. Carbohydrates Monosaccharides • The letters D and L are used to label all monosaccharides, even those with multiple stereogenic (chiral) centers. • The configuration of the stereogenic center furthest from the carbonyl group determines whether the monosaccharide is D- or L-.

19. Fischer Projection • In Fischer Projections, the "D" isomer will have the hydroxyl (-OH) functional group located on the right-hand side of the chiral C. • Note that the D/L nomenclature has nothing to do with optical rotation activity of the structure; this is indicated by the use of (+) or (-). • The majority of saccharides in nature have the "D" isomer

21. Carbon #1 is the end closest to the keto group • Carbon #4 is the highest chiral carbon and determines the "L" or "D" isomer nomenclature for the saccharide. • Carbon #3 is also chiral, and its chirality determines the common name . • Carbon #2 is not chiral, neither is carbon 1, or carbon 5. • For ketoses, the smallest chain length that would include a chiral center is four carbons (a ketotetrose, or tetrulose).

22. Stereochemistry terms: • If isomers are mirror images, then they are enantiomers • If isomers contain more than one chiral center and are not mirror images, then they are diastereomers • If carbohydrate isomers differ at only a single chiral center, then they are epimers. (epimers are a special category of diastereomers)

23. Reaction of Monosaccharide • This reaction is promoted in the presence of either acid or base • One of the subtleties of this reaction involves the stereochemistry • of the aldehyde and keto carbon - it goes from being achiral to chiral.

24. Alcohols react with ketones to produce hemiketals:

25. They have the potential to react to form cyclic forms -- pyranose • The resulting chirality of the aldehyde carbon (or keto carbon in ketoses) in the • cyclic structure can be either the a- or b- form. • This carbon is termed the anomeric carbon, and the a- and b- forms are anomers. • The ring structure representations are termed "Haworth Projections"

26. Epimers: Sugars that differ only by the configuration about one C-atom are known as epimers. Eg. glucose and mannose, glucose and galactose. The interconversion of epimers is known as epimerization. Hemiacetals/Hemiketals: The OH groups of monosaccharides can react with either the aldehyde or ketone groups within the monosaccharides (intramolecularly) to form cyclic hemiacetals or hemiketals This leads to the Formation of Ring structures - a 6-membered derivative of pyran ring or a 5-membered furan ring. The sugar is then in the Pyranose or Furanose form. Eg. D-Glucose also called D-Glucopyranose, D-Fructose – D-Fructofuranose

27. Structure of monosaccharide cont’d: • It is difficult to represent the steric arrangement of the cyclic structures by Fischer convention (horizontal bonds in front of the plane of paper, vertical bonds in back), so Haworth convention is frequently used, in which the ring is depicted on edge. • The conversion of the linear structure to the ringed structurecreatesan additional asymmetric centre at C-atom 1. So if the structure of D-Glucopyranose is depicted as a Haworth projection, the OH group on C-1 can point either downwards or upwards. • If it points downward, it is called α-D-Glucopyranose. If it points upward, it is called β–D-Glucopyranose

28. http://www.biologie.uni-hamburg.de/b-online/e16/16g.htm

29. The α– and β– forms are known as ANOMERS. They differ only in the configuration around C-1 which is called the ANOMERIC C-atom for glucose. For fructose, the anomeric C-atom is C-2 • Sugars contain usually one or more asymmetric C-atom, i.e. carbon atoms that carry four different substituents. Such atoms are optically active i.e. they shift the plane of polarized light. Sugars with more than one asymmetric carbon atom have 2nstereo-isomers (n is the number of asymmetric C-atoms). • With the introduction of an additional asymmetric centre, n =5, so the number of possible isomers of glucopyranose is 25 = 32.

30. Examples of Hexoses

31. The Haworth convention is useful for many purposes, but it is an oversimplification and does not represent the actual conformation of the pyranose and furanose rings, because the true conformations of these rings are not planar • The pyranose ring may assume a boat or chair conformation. The preferred conformation of pyranose structures is the chair. • The β-form is more stable than the α-form and predominates in solution.

32. CYCLIC STRUCTURES AND AROMATIC FORMS • Monosaccharides have the ability to form cyclic structures with formation of an additional asymmetric center. • Alcohols react readily with aldehydes to form hemiacetals • Thus we have PYRANOSE and FURANOSE structure.

33. CYCLIC STRUCTURE AND ANOMERIC FORMS

34. CYCLIC STRUCTURES AND ANOMERIC FORMS

35. REACTION OF MONOSACCHARIDES • A variety of chemical and enzymatic reactions produce derivatives of the simple sugars e.g SUGAR ACIDS O O RC H + Cu2+ + 5OH- RC O- + Cu2O + 3H2O Aldehyde Carboxylate Sugar with free anomeric carbon atoms are reasonably good reducing agents. Such reactions convert sugar to sugar acids aldose to an aldonic acid e.g gluconic acid

36. Reactions at the Carbonyl—Oxidation • Aldoses will react with Benedict’s reagent. • Benedict’s reagent uses blue Cu2+ which is reduced to a brick red solid (Cu2O) in a positive test. • Ketoses also give positive tests as they contain an a-hydroxy ketone. • Hemiacetals do not react with Benedict’s reagent--it is only the non-cyclic form of the sugar that reacts. • Carbohydrates that can be oxidized with Benedict’s reagent are called reducing sugars. • Those that do not react are called nonreducing sugars.

37. DERIVATIVES OF MONOSACCHARIDES • DIABETES MELLITUS is a condition that causes high levels of glucose in urine and blood and frequent analysis of reducing sugar in diabetic patients is an important part of the diagnosis and treatment of this disease ------ basis of over the counter kits • Monosaccharides can be oxidized enzymatically at C6, yielding URONIC ACID such as D-glucuronic acid

38. DERATIVES OF MONOSACCHARIDES

39. SUGAR ALCOHOLS • Sugar alcohols can be prepared by the mild reduction (with NaBH4 or similar agents) of the carbonyl groups of aldoses and ketoses.

40. SUGAR ALCOHOLS • Sugar alcohols , or alditols, are designated by the addition of –itol to the name of the parent sugar. • Alditols are characteristically sweet tasting and sorbitol, mannitol, and xylitol are widely used to sweeten sugarless gums and mints. • Sorbitol build up in the eyes of diabetics is implicated in cataract formation.

41. DEOXY SUGARS • The deoxy sugars are monosaccharides with one or more hydroxyl groups replaced by hydrogens. • Examples are:- 2-Deoxy-D-ribose – constituent of DNA in all living things.- L-Fucose – components of cell walls.- L-Rhamnose - components of cell walls.

43. DEOXY SUGARS • Rhamnose is also a component of the highly toxic cardiac glycoside ouabain – East African arrow poison.

44. SUGAR ESTERS • Phosphate esters of glucose, fructose, and other monosaccharides are important metabolic intermediates. • The ribose moiety of nucleotides such as ATP and GTP is phosphrylated at the 5’-position.

45. Phosphate Esters Phosphoric acid & anhydrides can form phosphate esters.

46. SUGAR ESTERS

47. AMINO SUGARS • Amino sugars contain an amino group (instead of a hydroxyl) at the C-2 position e.g. D-glucosamine and D-galactosamine found in many oligo- and polysaccharides. • Muramic acid and neuraminic acid are glucosamines linked to three-carbon acids at the C-1 and C-3 positions. • They are components of the polysaccharides of cell membranes of higher organisms and also bacterial cell walls.

48. End of Pt 1

49. References • http://www.mikeblaber.org/oldwine/BCH4053/Lecture12/Lecture12.htm retrieved on 11/8/12 @ 5:25 pm • Aspect of lecture was adapted from lecture material created by Dr. Mellissa Sanderson and Dr. Andrew Lamm and was modified by Dr. Deon. Bennett.