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CARBOHYDRATES 1 CARBOHYDRATES Empirical formula: C x (H2O)y 2 CARBOHYDRATES- WHERE ARE THEY ? In solid parts of: plants, up to 80% animals, do not exceed 2% In plants: – mainly as a storage material (starch) – building material (cellulose) In animals: – source of energy – building material: • skeleton of invertebrates and mushrooms (chitin – protective polysaccharide substance) • structural function in vertebrates (glycosaminoglycans) [ Invertebrates – animals without skeleton ] 3 CARBOHYDRATES CLASSIFICATION Monosaccharides – simple sugars with multiple OH groups. Carbohydrates which cannot be decomposed to other carbohydrate components Disaccharides – 2 monosaccharides covalently linked. During hydrolysis they degrade to two monosaccharides, ex.: maltose, saccharose Oligosaccharides – a few monosaccharides covalently linked; during hydrolysis they degrade to 3 to 10 units of monosaccharides, ex. :maltotriose Polysaccharides – polymers consisting of chains of monosaccharide or disaccharide units. During hydrolysis they degrade to over 10 molecules of monosaccharides, ex.: starch, glycogen. 4 Carbohydrates - occurrence Proteins + short chains of carbohydrates– glycoproteins Proteins + long chains of carbohydrates – proteoglycans glycocalyx – extracellular structure : glycoproteins + proteoglycans + glycolipids - - protects the surface of the cells against mechanical and chemical damages facilitates the movement of motile cells prevents from agglomeration of cells, and from sticking to vessel walls acts as mutual recognition sites between cells 5 PHYSICAL PROPERTIES OF MONOSACHARIDES COLORLESS, ODOURLESS USUALLY TASTE SWEET VERY WELL SOLUBLE IN WATER ROTATE THE PLANE OF POLARIZED LIGHT CHEMICALLY NEUTRAL (NO ACIDITY OR BASICITY) 6 MONOSACHARIDES - NOMENCLATURE Monosaccharides containing: aldehyde group - are called - aldoses ketone group - are called - ketoses Aldoses (ex, glucose) have an aldehyde group at one end. H Ketoses (ex., fructose) have a ketone group, usually at C2. O C H C CH2OH OH HO C H H C OH H C OH CH2OH D-glucose C O HO C H H C OH H C OH CH2OH D-fructose 7 TYPES OF MONOSACHARIDES ISOMERISM 1. 2. 3. 4. 5. 6. Configuration of D and L Optical isomerism Piranoses and furanoses Anomers a and b Epimers Constitutional isomers – aldoses and ketoses 8 CONFIGURATION D and L Molecules of glyceraldehyde are enantiomers. Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms (constitution), but differ (only) in the three-dimensional orientations of their atoms in space. Are also called mirror images (enantiomers). • if certain compound can be transformed to one of glyceraldehyde isomers then this compound belongs to D or L compounds. • D or L does not depend on rotation of polarized light. 9 ISOMERS D and L L-glyceraldehyde D-glyceraldehyde O O 1C 1C –H –H H – 2C – OH HO – 2C – H 3CH OH 2 3CH OH 2 1CHO L-glucose 2 HO – C – H H – 3C – OH HO – 4C – H 5 HO – C – H 6CH OH 2 D and L symbols determine sugars configuration: - hydroxyl group on the penultimate carbon counting from aldehyde group. Reference is glyceraldehyde. 1CHO H– – OH HO – 3C – H H – 4C – OH 5 H – C – OH 6CH OH 2 2C D-glucose 10 TYPE L ISOMERS L-iduronic acid Fucose L-fucose-1,6-N-acethyloglucosamine a-D-fukoza b-L-fukoza 11 OPTICAL ISOMERISM OF MONOSACHARIDES Amount of enantiomer pairs and diastereoisomers depends on active centers amount. CHO *CHOH *CHOH *CHOH *CHOH CH2OH For 4 centers the amount of enantiomers and diastereoisomers are 24=16 12 FAMILY OF D-aldose D-(+)- aldehyd glicerynowy 13 Hemiacetal & hemiketal formation H An aldehyde can react with an alcohol to form a hemiacetal. C H O + R' OH R' O R aldehyde C OH R alcohol hemiacetal R A ketone can react with an alcohol to form a hemiketal. C R O + "R OH R' ketone "R O C OH R' alcohol hemiketal 14 Pentoses and hexoses can form rings, as the ketone or aldehyde group reacts with a distal OH. Glucose forms an intra-molecular hemiacetal, as the C1 aldehyde group & C5 OH group reacts, to form a 6membered pyranose ring, named after pyran. C1 is a new asymmetric center. 1 H 2 HO 3 H 4 H 5 6 CHO C OH C H C OH (linear form) C OH D-glucose CH2OH 6 CH2OH 6 CH2OH 5 H 4 OH H OH 3 H O H H 1 2 OH OH Alfa DaD-glucose α-D-glucopyranoses glukopiranoses 5 H 4 OH H OH 3 H O OH H 1 2 H OH b-D-glucose β-D glucopyranoses Diastereoisomers = anomers = they differ from each other with 15 configuration at C1 atom only, and have different physical properties CH2OH 1 HO H H 2C O C H C OH C OH 3 4 5 6 HOH2C 6 CH2OH D-fructose (linear) H 5 H 1 CH2OH O 4 OH HO 2 3 OH H a-D-fructofuranose Fructose forms either: 6-membered pyranose ring, in reaction of the C2 keto group with the OH on C6, or a 5-membered furanose ring, in reaction of the C2 keto group with the OH on C5. 16 6 CH2OH 6 CH2OH 5 H 4 OH H OH 3 H O H H 1 2 OH a-D-glucose α D-glukopyranose OH 5 H 4 OH H OH 3 H O OH H 1 2 H OH D-glucose β-Db-glucopyranose Cyclization of glucose produces a new asymmetric center at C1. This two stereoisomers are called anomers, a & b. Haworth projections represent the cyclic forms of sugars (planar rings, with the OH at the anomeric C1): a (OH below the ring) b (OH above the ring). 17 H OH 4 H OH 6 H O HO HO H O HO H HO 5 3 H H 2 H OH 1 OH a-D-glucopyranose H OH OH H b-D-glucopyranose Because of the tetrahedral nature of carbon bonds, pyranose sugars actually have a "chair" or "boat" configuration, depending on the sugar. The above representation reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection. 18 Mutarotation Mutarotation is transformation of one anomeric form into another. An intermediate form is a chain form of monosaccharide. In D-glucose solution there is more b-D-glucopyranose. All its –OH groups have the most energetically beneficial equatorial position. 19 Monosaccharide epimers Epimers: Cn aldoza epimeryczna enediol Cn ketoza Cn aldoza diastereoisomers that differ from each other in one –OH position – Different than at C-1 in aldose – Different than at C-2 in ketose – Different than at last asymmetric carbon atom Pair of epimers: glucose and mannose 20 Glucose epimers D-fructose D-glucose D-mannose 21 Chemical properties of monosaccharides Reductive properties –only when free aldehyde or ketone group in saccharide molecule is present. In alkaline environment saccharides have reductive properties and ring can be opened In acidic environment saccharides are in cyclic form and there is no =CO group. Saccharides are oxidized to acids , while reduce other substances ex.: glucose is oxidized to gluconic acid 22 Chemical properties of monosaccharides Acid influence on saccharides – all saccharides with more than 4 carbon atoms during heating with strong acids are subjected to dehydration and cyclization Base influence on saccharides – in basic environment reductive saccharides get enolysed Osazone forming - saccharides with phenyl hydrazine form yellow, insoluble in water dihydrazones called osazones. 23 Osazone formation Epimers have the same osazone 24 Sugar derivatives CHO COOH CH2OH H H H C C C H C OH HO C H OH H C OH OH H C OH H C OH HO C H H C H C OH OH OH CH2OH D-ribitol CH2OH D-gluconic acid COOH D-glucuronic acid sugar alcohol – no aldehyde or ketone group; ex., ribitol. sugar acid - the aldehyde group at C1, or OH at C6, is oxidized to a carboxylic acid; ex., gluconic acid, glucuronic acid. 25 Sugar derivatives CH2OH CH2OH O H H OH H H OH H OH OH H NH2 a-D-glucosamine O H H H O OH OH H N C CH3 H a-D-N-acetylglucosamine amino sugar - an amino group substitutes for an hydroxyl group. An example is glucosamine. The amino group may be acetylated, as in N-acetylglucosamine. 26 H O H3C C O NH R H COO H R= OH H HC OH HC OH CH2OH OH H N-acetylneuraminate (sialic acid) N-acetylneuraminate (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate proton at physiological pH, as shown here. 27 Glycosidic Bonds The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compounds can bond together, releasing water to form a glycosidic bond: R-OH + HO-R' R-O-R' + H2O ex., methanol reacts with the anomeric OH in glucose to form methyl glucoside (methyl-glucopyranose). H OH H OH H2O H O HO HO H H H + CH3-OH H O HO HO H OH OH H OH a-D-glucopyranose H methanol OCH3 methyl-a-D-glucopyranose © 28 Glycosidic Bonds Glycosidic anomers © © 29 DISACCHARIDES Disaccharides consisting of two monosacharides, and connected by glycosidic bond are called O-glycosides. The most important are: • saccharose (present in honey, fruits), • lactose (present in milk), • maltose (product of enzymatic hydrolysis of starch), • cellobiose (product of cellulose hydrolysis). 30 Disaccharides: Maltose, a cleavage (split) product of starch (e.g., amylose), is a disaccharide with an a(1 4) glycosidic link between C1 - C4 OH of two glucoses. It is the a anomer (C1 O points down). 6 CH2OH 6 CH2OH H 5 O H OH 4 OH 3 H H H 1 H 4 4 maltose OH H H H 1 O 4 H 2 OH OH 2OH 5 O H OH H OH 1 H 2 3 cellobiose 1 OH H 3 H 2 H 6 CH O H OH H OH 3 OH 5 O O 2 6 CH2OH H 5 H OH Cellobiose, a product of cellulose breakdown, b anomer (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. © 31 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 an a configuration, (O points down from ring), the linkage is a(12). The full name of sucrose is a-D-glucopyranosyl-(12)-b-Dfructopyranose. Lactose, milk sugar, is composed of galactose & glucose, with b(14) linkage from the anomeric OH of galactose. Its full name is b-D-galactopyranosyl-(1 4)-a-D-glucopyranose. © 32 CH2OH H O H OH H H H 1 O OH 6CH OH 2 5 O H 4 OH 3 H OH H H H H 1 O H OH CH2OH CH2OH CH2OH H H H O H OH H O O H H O H OH H O OH 2 OH H OH H OH H H OH amylose Polysaccharides: Plants store glucose as amylose or amylopectin, glucose polymers, collectively called starch. Glucose storage in polymeric form minimizes osmotic effects. Amylose is a glucose polymer with a(14) bonds. The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the © reducing end. 33 CH2OH CH2OH O H H OH H H OH H O OH CH2OH H H OH H H OH H H OH CH2OH O H OH O H OH H H O O H OH H H OH H H O 4 amylopectin H 1 O 6 CH2 5 H OH 3 H CH2OH O H 2 OH H H 1 O CH2OH O H 4 OH H H H H O OH O H OH H H OH H OH Amylopectin is a glucose polymer with mainly a(14) bonds, but it also has branches formed by a(16) bonds. Branches are generally longer than shown above. The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur. © 34 CH 2OH CH 2OH O H H OH H H OH H O OH CH 2OH H H OH H H OH H H OH CH 2OH O H OH O H OH H H O O H OH H H OH H H O 4 glycogen H 1 O 6 CH 2 5 H OH 3 H CH 2OH O H 2 OH H H 1 O CH 2OH O H 4 OH H H H H O OH O H OH H H OH H OH Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin, but glycogen has more a(16) branches. The highly branched structure permits rapid glucose release from glycogen stores, e.g., in muscle during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants. 35 CH2OH H O H OH H OH H 1 O H H OH 6CH OH 2 5 O H 4 OH 3 H H H 1 2 OH O O H OH CH2OH CH2OH CH2OH H H O O H OH H OH O H O H OH H OH OH H H H H H H H OH cellulose Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose with b(14) bonds. Every next glucose is flipped over, due to b linkages. This promotes forming of intra-chain and inter-chain H-bonds and van der Waals interactions, that cause cellulose chains to be straight & rigid, and pack with a crystalline arrangement in thick bundles - microfibrils. Schematic of arrangement of cellulose chains in a microfibril.36 CH 2OH D-glucuronate 6COO H 4 6 5 H OH 3 H H 2 OH 1 H H OH O O H 4 O H 5 3 H 2 1 O H NH COCH 3 N-acetyl-D-glucosamine hyaluronate Glycosaminoglycans (mucopolysaccharides) are linear polymers of repetitive disaccharides. Can be covalently bound to a protein to form proteoglycans. The constituent monosaccharides tend to be modified with: acidic groups, amino groups, sulfated hydroxyl groups,etc. Glycosaminoglycans tend to be negatively charged because of the presence of acidic groups. It is important component of connective tissues. Some examples of glycosaminoglycan in nature include heparin as an anticoagulant , hyaluronic acid as a component of the synovial fluid lubricant in body joints, and chondroitins, which can be found in connective tissues, cartilage, and tendons. 37 CH 2OH D-glucuronate 6 6COO H 4 5 H OH 3 H H 2 OH 1 H H OH O O H 4 O H 5 3 H 2 1 O H NH COCH 3 N-acetyl-D-glucosamine hyaluronate Hyaluronate (hyaluronic acid) is a glycosaminoglycan with a repeating disaccharide motive consisting of two glucose derivatives, glucuronate (glucuronic acid) & N-acetylglucosamine. The glycosidic linkages are b(13) & b(14). 38 core protein heparan sulfate glycosaminoglycan transmembrane a-helix cytosol Proteoglycans are glycosaminoglycans that are covalently linked to serine residues of specific core proteins. The glycosaminoglycan chain is synthesized by sequential addition of sugar residues to the core protein. 39 N-sulfo-glucosamine-6-sulfate iduronate-2-sulfate CH2OSO3 H H COO OH O O H O H H OH H H H H OSO3 O H NHSO3 heparin or heparan sulfate - examples of residues Heparan sulfate is initially synthesized on a membraneembedded core protein as a polymer of alternating N-acetylglucosamine and glucuronate residues. Later, in segments of the polymer, glucuronate residues may be converted to the sulfated sugar iduronic acid, while Nacetylglucosamine residues may be deacetylated and/or sulfated. 40 PDB 1RID Heparin, a soluble glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is more highly sulfated. When released into the blood, it inhibits clot (coagulation) formation by interacting with the protein antithrombin. Heparin has an extended helical conformation. heparin: (IDS-SGN)5 Charge repulsion by many negatively charged groups may contribute to this conformation. Heparin (shown) has 10 residues, alternating IDS (iduronate-2sulfate) & SGN (N-sulfo-glucosamine-6-sulfate). 41 Proteins involved in signaling & adhesion at the cell surface recognize & bind heparan sulfate chains. ex., binding of some growth factors (small proteins) to cell surface receptors is enhanced by their binding also to heparan sulfates. Heparan sulfate sulfatases may remove sulfate groups at particular locations on heparan sulfate chains to alter affinity for signal N-sulfo-glucosamine-6-sulfate iduronate-2-sulfate proteins, ex., CH2OSO3 H growth factors. H COO OH O O H O H H OH H H H © H OSO3 O H NHSO3 42 heparin or heparan sulfate - examples of residues Glycosidic bond C CH2OH Oligosaccharides that are covalently attached to proteins or to membrane lipids may have linear or branched chains. O H H OH O CH2 CH NH H O serine residue O H OH H HN C CH3 b-D-N-acetylglucosamine O-linked oligosaccharide chains of glycoproteins vary in complexity. They bind to a protein via a glycosidic bond between a sugar residue & a serine or threonine OH. O-linked oligosaccharides play a role in recognition, interaction, and enzyme regulation. 43 CH2OH O O H H OH HN C HN CH2 C H H OH H HN C CH3 O N-acetylglucosamine Initial sugar in N-linked glycoprotein oligosaccharide Asn CH O HN HC R C O X HN HC R C O Ser or Thr N-linked oligosaccharides of glycoproteins tend to be complexed and branched. First N-acetylglucosamine is linked to a protein via the sidechain N of an asparagine residue in a particular 3-amino acid sequence. 44 NAN NAN NAN Gal Gal Gal NAG NAG NAG Man Man Man Key: NAG NAG Asn N-linked oligosaccharide Fuc NAN = N-acetylneuraminate Gal = galactose NAG = N-acetylglucosamine Man = mannose Fuc = fucose Additional monosaccharides are added, and the N-linked oligosaccharide chain is modified by removal and addition of residues, to yield a characteristic branched structure. 45 The End 46