Published on February 22, 2014
CARBOHYDRATE CHEMISTRY: CARBOHYDRATE CHEMISTRY PowerPoint Presentation: LETS LEARN SOME GREEK!!!! The name glucose comes from the Greek word glykys (γλυκύς), meaning "sweet", plus the suffix "-ose" which denotes a sugar 4 chiral centers give 2 4 = the 16 stereoisomer s of hexose sugars. Chirality , or " handedness ", Greek, ( χειρ) , kheir : "hand” chiral carbons are enantiomers Alpha α and Beta β are letters in the Greek alphabet Come on, let’s go on ca ! GrandpaVa ’s hotels are everywhere! PowerPoint Presentation: σα κχ αρων Greek “ sakcharon ” = sugar PowerPoint Presentation: Carbohydrates • Carbohydrates , or saccharides ( saccharo is Greek for ―sugar) are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis. • Carbohydrates include not only sugar, but also the starches that we find in foods, such as bread, pasta, and rice. • The term ―carbohydrate comes from the observation that when you heat sugars, you get carbon and water (hence, hydrate of carbon ). PowerPoint Presentation: Carbohydrates and Biochemistry •Carbohydrates are compounds of tremendous biological importance: –they provide energy through oxidation –they supply carbon for the synthesis of cell components –they serve as a form of stored chemical energy –they form part of the structures of some cells and tissues •Carbohydrates, along with lipids, proteins, nucleic acids, and other compounds are known as biomolecules because they are closely associated with living organisms. PowerPoint Presentation: Glucose (a monosaccharide) Plants: photosynthesis chlorophyll 6 CO 2 + 6 H 2 O C 6 H 12 O 6 + 6 O 2 sunlight (+)-glucose (+)-glucose starch or cellulose respiration C 6 H 12 O 6 + 6 O 2 6 CO 2 + 6 H 2 O + energy PowerPoint Presentation: Animals plant starch (+)-glucose (+)-glucose glycogen glycogen (+)-glucose (+)-glucose fats or aminoacids respiration (+)-glucose + 6 O 2 6 CO 2 + 6 H 2 O + energy CLASSIFICATION:: CLASSIFICATION: 1- Monosaccharides (simple sugars): They can not be hydrolyzed into simpler units. E.g. glucose, galactose,ribose 2- Oligosaccharides ( oligo = few): contain from two to ten monosaccharide units joined in glycosidic bonds. e.g. disaccharides (2 units) e.g. maltose and sucrose, trisaccharides (3 units).....etc. 3-Polysaccharides (poly = many): Also known as glycans . They are composed of more than ten monosaccharide units e.g. starch, glycogen, cellulose.....etc. Monosaccharides: Monosaccharides CLASSIFICATION OF MONOSACCHARIDES 1- According to the number of carbon atoms : . Trioses , contain 3 carbon atoms. Tetroses , contain 4 carbon atoms. Pentoses , contain 5 carbon atoms. Hexoses , contain 6 carbon atoms. Heptoses , contain 7 carbon atoms. Octoses . contain 8 carbon atoms. PowerPoint Presentation: 2- According to the characteristic carbonyl group (aldehyde or ketone group): - Aldo sugars : aldoses : Contain aldehyde group e.g. glucose, ribose, erythrose and glyceraldehydes . - Keto sugars : ketoses : Contain ketone group e.g. fructose , ribulose and dihydroxy acetone . Forms of Monosaccharides:: Forms of Monosaccharides: Trioses:: Trioses : D- glyceraldehyde Dihydroxyacetone Tetroses: : Tetroses: D - erythrose Ketose CH 2 OH C = O H -C – OH CH 2 OH D - erythrulose Pentoses:: Pentoses: Hexoses:: Hexoses: Heptoses: is a ketose sugar: Heptoses: is a ketose sugar D - sedoheptulose It is aptly said that Glyceraldehyde is the ‘Reference Carbohydrate’: It is aptly said that Glyceraldehyde is the ‘Reference Carbohydrate’ PowerPoint Presentation: 20 Cyanohydrin Formation and Chain Extension. Kiliani -Fischer Synthesis - a series of reaction that extends carbon chain in a carbohydrate by one carbon and one chiral centre . PowerPoint Presentation: 21 tartaric acid D-(-)-tartaric acid Determination of carbohydrate stereochemistry PowerPoint Presentation: 22 PowerPoint Presentation: 23 PowerPoint Presentation: 24 Physical Properties of Monosaccharides: Physical Properties of Monosaccharides Most monosaccharides have a sweet taste (fructose is sweetest; 73% sweeter than sucrose). They are solids at room temperature. They are extremely soluble in water: Despite their high molecular weights, the presence of large numbers of OH groups make the monosaccharides much more water soluble than most molecules of similar MW. Glucose can dissolve in minute amounts of water to make a syrup (1 g / 1 ml H 2 O ). PowerPoint Presentation: Sugar Relative Sweetness Type Lactose 0.16 Disaccharide Galactose 0.22 Monosaccharide Maltose 0.32 Disaccharide Xylose 0.40 Monosaccharide Glucose 0.74 Monosaccharide Sucrose 1.00 Disaccharide Invert sugar1.30 Mixture of glucose and fructose Fructose 1.73 Monosaccharide ISOMERISM: ISOMERISM ENANTIOMER OPTICAL EPIMER ISOMER ANOMER ALDOSE-KETOSE ISOMER The Stereochemistry of Carbohydrates: The Stereochemistry of Carbohydrates Two Forms of Glyceraldehyde •Glyceraldehyde, the simplest carbohydrate, exists in two isomeric forms that are mirror images of each other: 10 PowerPoint Presentation: Stereoisomers • These forms are stereoisomers of each other. • Glyceraldehyde is a chiral molecule — it cannot be superimposed on its mirror image. The two mirror-image forms of glyceraldehyde are enantiomers of each other. Chirality and Handedness • Chiral molecules have the same relationship to each other that your left and right hands have when reflected in a mirror. 11 PowerPoint Presentation: Chiral Carbons Chiral objects cannot be superimposed on their mirror images —e.g., hands, gloves, and shoes. Achiral objects can be superimposed on the mirror images —e.g., drinking glasses, spheres, and cubes. Any carbon atom which is connected to four different groups will be chiral, and will have two nonsuperimposable mirror images; it is a chiral carbon or a center of chirality . –If any of the two groups on the carbon are the same, the carbon atom cannot be chiral . Many organic compounds, including carbohydrates, contain more than one chiral carbon. PowerPoint Presentation: Van’t Hoff’s 2 n rule When a molecule has more than one chiral carbon, each carbon can possibly be arranged in either the right-hand or left-hand form, thus if there are n chiral carbons, there are 2 n possible stereoisomers. Maximum number of possible stereoisomers = 2 n Can you tell no. of possible stereoisomers of CHOLESTEROL? D and L isomers (Enantiomers): D and L isomers (Enantiomers) Enantiomers : They are the mirror image of each others. CHO CHO H - C– OH HO-C-H CH 2 OH CH 2 OH D-Glyceraldehyde L-Glyceraldehyde PowerPoint Presentation: 34 Carbohydrates are designated as D- or L- according to the stereochemistry of the highest numbered chiral carbon of the Fischer projection. If the hydroxyl group of the highest numbered chiral carbon is pointing to the right, the sugar is designated as D ( Dextro : Latin for on the right side ). If the hydroxyl group is pointing to the left, the sugar is designated as L ( Levo : Latin for on the left side ). Most naturally occurring carbohydrates are of the D-configuration. What’s So Great About Chiral Molecules?: What’s So Great About Chiral Molecules ? Molecules which are enantiomers of each other have exactly the same physical properties (melting point, boiling point, index of refraction, etc.) but not their interaction with polarized light . •Polarized light vibrates only in one plane; it results from passing lights through polarizing filter Optical Activity: Optical Activity A levorotatory ( – ) substance rotates polarized light to the left [e.g., l -glucose; (-)-glucose ]. •A dextrorotatory ( + ) substance rotates polarized light to the right [e.g., d -glucose; (+)-glucose ]. •Molecules which rotate the plane of polarized light are optically active. •Many biologically important molecules are chiral and optically active. Often, living systems contain only one of the possible stereochemical forms of a compound, or they are found in separate system. –D-lactic acid is found in living muscles; D-lactic acid is present in sour milk. –In some cases, one form of a molecule is beneficial, and the enantiomer is a poison (e.g., thalidomide). –Humans can metabolize D- monosaccharides but not L-isomers; only L-amino acids are used in protein synthesis PowerPoint Presentation: 38 The Aldotetroses . Glyceraldehyde is the simplest carbohydrate (C 3 , aldotriose , 2,3-dihydroxypropanal). The next carbohydrate are aldotetroses (C 4 , 2,3,4-trihydroxybutanal). PowerPoint Presentation: 39 Aldopentoses and Aldohexoses . Aldopentoses : C 5 , three chiral carbons, eight stereoisomers Aldohexoses: C 6 , four chiral carbons, sixteen stereoisomers PowerPoint Presentation: 40 Fischer Projections and the D-L Notation. Representation of a three-dimensional molecule as a flat structure. Tetrahedral carbon represented by two crossed lines: vertical line is going back behind the plane of the paper (away from you) horizontal line is coming out of the plane of the page (toward you) carbon substituent (+)- glyceraldehyde (-)- glyceraldehyde PowerPoint Presentation: 41 Manipulation of Fischer Projections Fischer projections can be rotate by 180° (in the plane of the page) only! 180° 180° Valid Fischer projection Valid Fischer projection PowerPoint Presentation: 42 a 90° rotation inverts the stereochemistry and is illegal! 90° This is not the correct convention for Fischer projections Should be projecting toward you Should be projecting away you This is the correct convention for Fischer projections and is the enantiomer PowerPoint Presentation: 43 If one group of a Fischer projection is held steady, the other three groups can be rotated clockwise or counterclockwise. 120° 120° 120° 120° PowerPoint Presentation: 44 Cyclic Forms of Carbohydrates: Furanose Forms. (Ch. 17.8) PowerPoint Presentation: 45 In the case of carbohydrates, cyclization to the hemiacetal creates a new chiral center . Converting Fischer Projections to Haworth formulas PowerPoint Presentation: 46 PowerPoint Presentation: 47 Cyclic Forms of Carbohydrates: Pyranose Forms. glucopyranose ribopyranose Two types of pyranose form: Two types of pyranose form Chair form Boat form 48 CHAIR form is thermodynamically more stable: CHAIR form is thermodynamically more stable Substituents on the ring carbons may be either axial (ax), projecting parallel to the vertical axis through the ring , or equatorial ( eq ), projecting roughly perpendicular to this axis. Two conformers such are these are not readily Interconvertible without breaking the ring. However, when the molecule is “stretched” ( by atomic force microscopy), an input of about 46 kJ of energy per mole of sugar can force the interconversion of chair forms . Generally , substituents in the equatorial positions are less sterically hindered by neighboring substituents , and conformers with bulky substituents in equatorial positions are favored. Another conformation, the “boat” is seen only in derivatives with very bulky substituents. PowerPoint Presentation: 50 Mutarotation and the Anomeric Effect. The hemiacetal or hemiketal carbon of the cyclic form of carbohydrates is the anomeric carbon . Carbohydrate isomers that differ only in the stereochemistry of the anomeric carbon are called anomers . Mutarotation : The - and - anomers are in equilibrium, and interconvert through the open form. The pure anomers can be isolated by crystallization. When the pure anomers are dissolved in water they undergo mutarotation , the process by which they return to an equilibrium mixture of the anomer . -D-Glucopyranose (36%) ( -anomer: C1-OH and CH 2 OH are trans) -D-Glucopyranose (64%) ( -anomer: C1-OH and CH 2 OH are cis) PowerPoint Presentation: 51 α , D-glucose D- glucose , D-glucose (+110 ) (+52.5) (+17.2 ) Epimers:: Epimers : Two monosaccharides differ only in the configuration around one specific carbon atom. The D-glucose and D-mannose are epimers with respect to carbon atom 2, D-glucose and D- galactose are epimers with respect to carbon atom 4. Aldose-Ketose isomerism:: Aldose- Ketose isomerism : Two monosaccharides have the same molecular formulae but differ in their functionl groups . one has an aldehyde group (aldose e.g. glucose) the other has a ketone group (Ketose e.g. fructose). Monosaccharides of physiologic importance : Monosaccharides of physiologic importance 1-Pentoses: : 1-Pentoses: * -D-ribose is a structural element of ribonucleic acid (RNA)and coenzymes e.g. ATP, NAD, NADP and others. D-ribose-phosphate and D-ribulose-5-phosphate are formed from glucose in the body (HMS). * 2-deoxy D-ribose enters in the structure of DNA . * D- lyxose : constituent of lyxoflavin in human myocardium.Lot of experiments are going to establish it as a potent myocardial infarction marker. 2-Hexoses:: 2-Hexoses: 1- D-glucose (grape sugar, Dextrose as D-glucose is dextrorotatory ). It is the sugar carried by the blood (normal plasma level 70-100 mg/dL ) and the principal one used by the tissues. It is found in fruit juices obtained by hydrolysis of starch, cane sugar, maltose and lactose. PowerPoint Presentation: 2- D-Fructose (honey sugar = levulose as D-fructose is levorotatory). It is found in fruit juices (fruit sugar ) Obtained from sucrose by hydrolysis. It is present in the semen in pyranose form 3- D-galactose: It is a constituent of galactolipids and glycoprotein in cell membranes and extracellular matrix. Important properties of monosaccharides: Important properties of monosaccharides Iodocompounds: Iodocompounds Glucose when heated with conc. Hydroiodic acid loses all its oxygen and converted to Iodohexane . This suggests that glucose has no branched chain. Glucose conc.HI Iodohexane Ester Formation: 62 Ester Formation The – OH groups of monosaccharides can form esters with acids (phosphate & sulfate). Phosphate esters: Glucose – 1 – phosphate Glucose – 6 – phosphate Sulfate esters: Galactose – 3 – sulfate Glucose – 6 - Phosphate: 63 Glucose – 6 - Phosphate Sugar as reducing agent: Sugar as reducing agent The monosaccharides and most of the disaccharides are rather strong reducing agents, particularly at high pH. At alkaline pH aldehyde or keto group tautomerizes to form highly reactive ENEDIOL group. This group has strong reducing property. H C OH C OH 1,2 enediol form R 64 Trommer’s test-precursor of BENEDICT’S test: Trommer’s test-precursor of BENEDICT’S test CuSO 4 + 2NaOH Cu(OH) 2 + Na 2 SO 4 (bluish white) 2Cu(OH) 2 2 CuOH + H 2 O + O Cu 2 O + H 2 O (red) Trommer’s test is not convenient enough and later Benedict’s test replaced it. 65 Copper(I) oxide (red-orange ppt): Copper(I) oxide (red-orange ppt ) Benedict’s reagent contains CuSO 4 ,sodium carbonate and sodium citrate. Ammoniac silver nitrate solution may be reduced to metallic silver, producing a mirror- TOLLEN’s Test Alkaline Bismuth solution, known as Nylander’s solution , deposits black metallic bismuth on reduction. Picric acid in alkaline medium is reduced to picramic acid. Color changes from yellowish orange to mahogany red. In acid solution sugar reduces less vigorously.Barfoed’s test utilizes this fact for distinguishing monosaccharides from reducing disaccharides. 66 Benedict’s Reagent (blue) Reaction with strong alkalis : Reaction with strong alkalis The sugar caramelises and produces a series of decomposition products,yellow and brown pigments develop,salts may form, many double bonds are formed between C-atoms. 67 Action of strong acid on monosaccharides: Action of strong acid on monosaccharides With conc. Mineral acids the monosaccharides get decomposed. Pentoses yield cyclic aldehyde ‘ furfural’. Hexoses are decomposed to ‘ hydroxymethyl furfural ’ which decomposes further to produce laevulinic acid,CO,CO 2 68 The furfural products can condense with certain organic phenols to form compounds having characteristic color. It forms the basis of certain tests used for detection of sugars. Molisch’s Test: With alpha-naphthol (in alcoholic solution)gives purple ring. A sensitive reaction but not specific. It is used as Group test of carbohydrate. Seliwanoff’s test:With resorcinol, a cherry red colour is produced. It is characteristic of D-fructose. Other tests are anthrone test, Bial-orcinol test: The furfural products can condense with certain organic phenols to form compounds having characteristic color. It forms the basis of certain tests used for detection of sugars. Molisch’s Test: With alpha-naphthol (in alcoholic solution)gives purple ring. A sensitive reaction but not specific. It is used as Group test of carbohydrate. Seliwanoff’s test: With resorcinol, a cherry red colour is produced. It is characteristic of D-fructose. Other tests are anthrone test, Bial-orcinol test 69 OSAZONE formation: OSAZONE formation Emil Fischer done this job to detect various sugars. Used to differentiate simple sugar by their varied form of osazone and rate of osazone formation. PREPARATION: they are obtained by adding a mixture of phenylhydrazine hydrochloride and sodium acetate to the sugar solution and heating in boiling water bath for 30 to 45 mins.The solution is allowed to cool slowly by itself.crystals are formed .A coverslip preparation is made on a clean slide and seen under microscope. 70 PowerPoint Presentation: 71 Mullikin’s figures: Mullikin’s figures sugar Glucose Fructose Sucrose Maltose Lactose Time(minutes) 4-5 2 30-45 after hydrolysis Osazone soluble in hot water Osazone soluble in hot water 72 Principle: Principle Free carbonyl group of sugars react eith phenylhydrazine to form phenylhydrazone With excess phenylhydrazine , the adjacent C-atom of carbonyl group react with phenylhydrazine to form yellow compounds called osazone . 73 PowerPoint Presentation: 74 PowerPoint Presentation: 75 Oxidation of sugar: Oxidation of sugar 1. Aldonic acid : oxidation of an aldoses with Br 2 -water converts the aldehyde group to a carboxyllic group D-Glucose D- gluconic acid 2.Saccharic acid or aldaric acid : oxidation of aldoses with conc.HNO 3 under proper conditions convert both aldehyde and primary alcohol group to –COOH group,forming dibasic sugar acids, the Saccharic acid or aldaric acid. D-Glucose D- Glucaric acid D- Galactose D- Mucic acid 76 PowerPoint Presentation: 3 . Uronic acid : When only the primary alcohol group of an aldose is oxidized to –COOH group, without oxidation of aldehyde group, a uronic acid is formed . D-Glucose D- Glucuronic acid D- galactose D- Galacturonic acid Due to presence of free –CHO group they exert reducing action. Biomedical importance 77 Reduction: Reduction Carbonyl groups can be reduced to alcohols (catalytic hydrogenation) Sweet but slowly absorbed Glucose is reduced to sorbitol (glucitol) Xylose can be reduced to xylitol Once reduced – less reactive; not absorbed PowerPoint Presentation: 79 Glceraldehyde & dihydroxyacetone to Glycerol . Ribose to Ribitol . Glucose to Sorbitol . Galactose to Dulcitol . Mannose to Mannitol . Fructose to Sorbitol & Mannitol PowerPoint Presentation: 80 Glycerol Present in the structure of many lipids. Ribitol Enters in the structure of Riboflavin. Myo -inositol One of the isomers of inositol. A hydroxylated cyclohexane. Present in the structure of a phospholipid termed phosphatidyl inositol. Interconversion of sugars: Interconversion of sugars Glucose, Fructose and Mannose differ from each other only arrond C1- C3.So they are interconvertible in weak alkaline solution such as Ba(OH) 2 or Ca (OH) 2. This is due to same ENEDIOL formation during tautomerization . This is called Lobry de Bruyn -Van Ekenstein Reaction 81 PowerPoint Presentation: 82 25.20: Epimerization, Isomerization and Retro- Aldol Cleavage. From Ch 18.10 Fructose is a reducTollen’s test) ing sugar (gives a positive Other sugar derivatives of biomedical importance: Other sugar derivatives of biomedical importance L-ascorbic acid Phytic acid Deoxy sugar Amino sugar Amino sugar acids Glycosides 83 L – Ascorbic acid: 84 L – Ascorbic acid O = C Due to lack of HO – C enzymes it bec - HO – C O omes a VITAMIN H – C for human beings HO – C - H CH 2 OH Glucuronic acid is reduced to L- Gulonic acid and then converted through L- Gulonolactone to L-Ascorbic acid in plants and most higher animals. Phytic acid: 85 Phytic acid The hexaphosphoric ester of inositol. Forms insoluble salts with Ca 2+ , Mg 2+ , Fe 2+ & Cu 2+ Prevent their absorption from diet in the small intestine. So it is better to avoid maize and legumes in diet of anaemic patient with iron rich diet or haematinic drugs. Deoxysugars: 86 Deoxysugars Deoxyribofuranose Present in DNA. L-Fucose 6-deoxy-L-galactose Important component of some cell membrane glycoproteins & blood group antigens. PowerPoint Presentation: 87 Aminosugars: 88 Aminosugars Formed from the corresponding monosaccharide by replacing the –OH group at C 2 with an amino (NH 2 ) group . Are important constituents of GAGs & some types of glycolipids eg gangliosides . Are conjugated with acetic acid &/or sulfate to form different derivatives. Aminosugars: 89 Aminosugars Glucosamine Galactosamine Mannosamine Glucosamine – 2,6 – bisulfate (heparin) N-acetyl-glucosamine (hyaluronic acid) N-acetyl-galactosamine (chondroitin sulfate) Amino sugar: Amino sugar Glycosylamine Anomeric –OH group is replaced by –NH2 e.g glucosylamine Glycosamine -OH group attached to carbon atom other than the anomeric one. e.g glucosamine 90 Glucosamine: Glucosamine 91 Aminosugars Acids: Aminosugars Acids Are formed of 6-C aminosugars linked to 3-C acid. Examples: Neuraminic acid : ( Mannosamine + Pyruvic acid) N- acetylneuraminic acid ( Sialic acid) Muramic acid (glucosamine + lactic acid) 92 Sialic Acid (NANA): 93 Sialic Acid (NANA) Enters in the structure of may glycolipids & glycoproteins . Forms an important structure of cell membrane & has many important functions: It is important for cell recognition & interaction. It is an important constituent of cell membrane receptors. It plays an important role in cell membrane transport systems. Neuraminic Acid: 94 Neuraminic Acid Glycosides: 95 Glycosides Formed by a reaction between the anomeric carbon (in the form of hemiacetal or hemiketal ) with alcohols or phenols . Are named according to the reacting sugar. Any glycosidic linkage is named according to the type of parent sugar eg glucosidic , galactosidic or fructosidic linkages. Types of Glycosides: 96 Types of Glycosides Monosaccharide units may condense in the form of di -, oligo - & polysaccharides where the second sugar reacts as an alcohol & condenses with the anomeric carbon by removal of H 2 O. A sugar may also condense with a non-sugar radical ( aglycon ) Nucleoside : (pentose sugar + nitrogenous base) Biomedically important Glycosides: Biomedically important Glycosides Cardiac glycosides: obtained from digitalis They all contain steroids as aglycone . Digitalis glycosides include digitoxin , gitoxin , gitalin and digoxin Digoxin is class V antiarrhythmic drug according to Vaughan Williams classification. Used in supraventricular arrhythmia especially heart failure with atrial fibrillation 100 PowerPoint Presentation: Contraindicated in ventricular tachycardia. Chemically, Digitonin 4Galactose + Xylose+digitogenin ( aglycone ) OUABAIN: It gains interest as class 1 C antiarrhythmic drug that inhibit active transport of sodium in myocardium in vivo. It prevents paroxysmal atrial fibrillation. PowerPoint Presentation: PHLORIDZIN: Obtained from the root and bark of apple tree. It blocks transport of sugar across mucosal cells of small intestine and renal tubular epithelium. Displaces Na+ from the binding site of carrier protein and prevents the binding of sugar molecule and produces glycosuria. STREPTOMYCIN , the well known antibiotic is also a Glycoside.