Carbohydrate Chemistry PDF

CARBOHYDRATES OCCURRENCE Carbohydrates are present in humans, animal tissues, plants and in micro-organisms. Carbohydrates are also present in tissue fluids, blood, milk, secretions and excretions of animals. 8/5/20...

CARBOHYDRATES OCCURRENCE Carbohydrates are present in humans, animal tissues, plants and in micro-organisms. Carbohydrates are also present in tissue fluids, blood, milk, secretions and excretions of animals. 8/5/2024 1 Biomedical Significance 1. Carbohydrates are the major source of energy for man. For example, glucose is used in the human body for energy production. 2. Some carbohydrates serve as reserve food material in humans and in plants. For example, glycogen in animal tissue and starch in plants serves as reserve food materials. 3. Carbohydrates are components of several animal structure and plant structures. In animals, carbohydrates are components of skin, connective tissue, tendons, cartilage and bone. In plants, cellulose is a component of wood and fiber. 4. Some carbohydrates are components of cell membrane and nervous tissue. 5. Carbohydrates are components of nucleic acids and blood group substances. 6. Carbohydrates are involved in cell-cell interaction. 7. Derivative of carbohydrates are drugs. For example, a glycoside ouabain is used in clinical medicine. Streptomycin an antibiotic is a glycoside. 8. Aminosugars, derivatives of carbohydrates are components of antibiotics like erythromycin and carbomycin. 9. Ascorbic acid, a derivative of carbohydrate is a water-soluble vitamin. 10. Bacterial invasion involves hydrolysis of mucopolysaccharides. 11. Survival of Antarctic fish in icy environment is due to presence of anti-freeze glycoproteins in their blood. 8/5/2024 2  Chemical Nature of Carbohydrates o Carbohydrates are polyhydroxy alcohols with a functional aldehyde or keto group. o They are represented with general formulae Cn(H2O)n. o Usually the ratio of carbon and water is one in most of the carbohydrates hence the name carbohydrate (Carbonhydrate). 8/5/2024 3  Classification of Carbohydrates Carbohydrates are classified into three major classes based on number of carbon chains present. They are: 1. Monosaccharides 2. Oligosaccharides 3. Polysaccharides All the three classes contain a saccharose group and hence the name saccharides. 8/5/2024 Saccharose group 4 Monosaccharides o Monosaccharides are those carbohydrates which can not be hydrolyzed to small compounds. o They are also called as simple sugars. o Monosaccharides containing three to nine carbon atoms occur in nature. Nomenclature o Monosaccharides have common (trivial) names and systematic names. o Systematic name indicates both the number of carbon atoms present and aldehyde or ketone group. o For example, glyceraldehyde is a simple sugars containing three carbon atoms and a aldehyde group. o Simple sugars containing three carbon atoms are referred as trioses. o In addition, sugars containing aldehyde group or keto group are called as aldoses or ketoses, respectively. o Thus, the systematic name for glyceraldehyde is aldotriose. Similarly, a simple sugar with three carbon atoms and a keto group is called as ketotriose. 8/5/2024 5 Some monosaccharides 8/5/2024 6 PROPERTIES OF MONOSACCHARIDES 1. Optical Isomerism All the monosaccharides except dihydroxyacetone contain at least one asymmetric carbon atom and hence they exhibit optical isomerism. The two optical isomers of glyceraldehyde containing one asymmetric carbon atom are D-glyceraldehyde and L-glyceraldehyde. The optical isomers are also called as enantiomers. The D and L forms of glyceraldehyde are. Enantiomers have equal and opposite specific rotations, which is why enantiomers are also sometimes called “optical isomers”. E.g., the specific rotation of (R)-malic acid is [α]20D +27° (c = 5.5, pyridine), exactly equal and opposite to that of (S)-malic acid. 8/5/2024 7  Further D and L-glyceraldehyde are used as parent compounds to designate all other sugars (compounds) as D or L forms. If a sugar has the same configuration as D-glyceraldehyde on the penultimate carbon atom then it is called as ‘D’ sugar. If a sugar has the same configuration as L-glyceraldehyde on the penultimate carbon atom then it is called as ‘L’ sugar. Usually, the hydroxyl group on penultimate carbon atom points to right in ‘D’ glucose and D-glyceraldehyde whereas it points to left in L-glucose and L- glyceraldehyde. Further D and L forms of glucose are mirror images like mirror images of glyceraldehyde. Though both forms of sugars are present in nature D-isomer is abundant and sugars present in the body are all D-isomers. L-fructose and L-rhamnose are two L-isomers found in animals and plants. O H O H C C H – C – OH HO – C – H HO – C – H H – C – OH H – C – OH HO – C – H H – C – OH HO – C – H CH2OH CH2OH D-glucose L-glucose 8/5/2024 8  Enantiomers – (mirror images but not superimposable) have identical chemical and physical properties except in chiral medium. Enantiomers rotate plane-polarized light in equal and opposite directions, which is why they are sometimes called “optical isomers”. A solution containing equal amounts of two enantiomers is known as a racemic mixture. Since the rotations from both enantiomers cancel out (like two equal and opposite vectors) racemic mixtures lack optical activity. 8/5/2024 9 8/5/2024 10 8/5/2024 11 8/5/2024 12 8/5/2024 13  2. Optical Activity Monosaccharides except dihydroxyacetone exhibit optical activity because of the presence of asymmetric carbon atom. If a sugar rotates plane polarized light to right then it is called as dextrorotatory. If a sugar rotates the plane polarized light to the left then it is called as levorotatory. Usually ‘+’ sign or ‘d’ indicates dextrorotation and ‘–’ sign or 1 indicates levorotation of a sugar. For example, D-glucose which is dextrorotatory is designated as D(+) glucose and D- fructose, which is levorotatory is designated as D(–) fructose. The letter ‘D’ does not indicate whether a given sugar is dextro or levorotatory. 8/5/2024 14  3. Epimers Are those monosaccharides that differ in the configuration of –OH group on 2nd, 3rd and 4th carbon atoms. Epimers are also called as diastereoisomers. Glucose, galactose and mannose are examples for epimers. Galactose is an epimer of glucose because, configuration of hydroxyl group on 4th carbon atom of galactose is different from glucose. Similarly, mannose is an epimer of glucose because configuration of hydroxyl group on 2nd carbon atom of mannose is different from glucose. Ribulose and xylulose are also epimers. They differ in the configuration of –OH group on third carbon atom. Diastereomers – (non mirror images and non- superimposable) have different physical properties (i.e. 8/5/2024 boiling points, melting points, densities, solubility) 15  Diastereomers 1 and 2 differ from each other in the absolute configuration at only one chiral center. Thus, 1 and 2 are epimers. 1 and 2 have the same molecular formula and the same structural formula and, therefore, stereoisomers. 1 and 2 are not mirror images of each other and, therefore, are diastereomers. In epimers the chiral carbon atoms whose absolute configuration makes the two compounds different 8/5/2024 are called the epimeric carbons. 16  4. Functional Isomerism Functional isomers have same molecular formulae but differ in their functional groups. For example, glucose and fructose have same molecular formulae C6H12O6, but glucose contains aldehyde as functional group and fructose contains keto group. Hence, glucose and fructose are functional isomers. This type of functional isomerism is also called as aldose-ketose isomerism because aldose is an isomer of ketose and vice versa. 8/5/2024 17 8/5/2024 18 5. Ring Structures In solution, the functional aldehyde group of glucose combines with hydroxyl group of 5th carbon atom. As a result a 6 numbered heterocyclic pyranose ring structure containing 5 carbons and one oxygen is formed. The linkage between aldehyde group and alcohol is called as ‘hemiacetal’ linkage. Similarly, a 5 numbered furanose ring structure is formed from fructose when keto group combines with hydroxyl group on 5 carbon atom. The linkage between keto and alcohol group is called ‘hemi ketal’ linkage. Both hemi acetal and hemi ketal are internal or intra molecular linkages. 8/5/2024 19 6. Anomers Those monosaccharides that differ in configuration of OH groups on carbonyl carbon or anomeric carbon are called anomers. Formation of ring structure of glucose generates anomers of glucose, which are designated as α and β forms. These two forms of glucose differ in the α-D-Glucopyranose β-D-Glucopyranose configuration of OH on carbonyl carbon or 1st carbon atom. In the α-form the hydroxyl group on anomeric carbon (1st carbon) atom points to the right where as in the β-form to the left. 8/5/2024 20  7. Mutarotation Monosaccharides containing asymmetric carbon atom rotate plane polarized light. When optical rotation for α-D-glucose is measured it will be 112° and on standing the rotation decreases slowly and attains a constant value +52.5°. Likewise when optical rotation for β-D-glucose is measured the rotation changes from initial +19° to +52.5°. The change in optical rotation when either form of glucose is allowed to stand in solution is called mutarotation. It is due to conversion of cyclic form of glucose to straight chain form. 8/5/2024 21  Important monosaccharides in the metabolic point of view are glucose, fructose, galactose, ribose, erythrose and glyceraldehyde. Glucose is found in several fruit juice blood of humans and in honey. Galactose is a part of lactose. Fructose is found in several fruit juices and honey. Commonly glucose is referred as dextrose. All monosaccharides containing free aldehyde or keto group reduces ions like Cu2+ under alkaline conditions. 8/5/2024 22 Biologically Important Sugar (Glucose) Derivatives Sugar derivatives of biological importance are sugar acids, sugar alcohols, deoxy sugars, sugar phosphates, amino sugars and glycosides. 1. Sugar acids Oxidation of aldo group of sugars produces aldonic acids. For example, oxidation of glucose produces gluconic and oxidation of terminal alcohol group (–OH sixth carbon atom) of glucose produces glucuronic acid or uronic acid. Uronic acids are components of mucopolysaccharides and required for detoxification. Ketoses are not easily oxidized. Vitamin C or ascorbic acid is also sugar acid. 2. Sugar alcohols Reduction of aldose and keto groups of sugar produces polyhydroxy alcohols or polyols. These polyols are intermediates of metabolic reactions. Other sugar alcohols are glycerol and inositol. The alcohols formed from glucose, galactose and fructose are sorbitol, galactitol and sorbitol, respectively. Assignment: (a) Give structural examples of Oxidation and reduction products of glucose. (b) Give structural examples of some derivatives of monosaccharides 8/5/2024 23 3. Deoxy sugars Those sugars in which oxygen of a hydroxyl group is removed leaving hydrogen. Deoxyribose is an example. It is present in nucleic acids. Fucose is another deoxy sugar present in blood group substances. 4. Sugar phosphates Breakdown of sugar in animals involves formation of sugar phosphates. Glucose-6-phosphate is an example for a sugar phosphate. 5. Amino sugars Those sugars in which an amino group is substituted for a hydroxyl group. D-glucosamine is an example for an amino sugar. Amino sugars are components of mucopolysaccharides, and antibiotics. 6. Glycosides (a) O-glycosides. When hydroxyl group on anomeric carbon of a sugar reacts with an alcohol (sugar) O-glycoside is formed. O-glycosidic linkage is present in disaccharides and polysaccharides. So, disaccharides, oligosaccharides and polysaccharides are O-glycosides. (b) N-glycosides. N-Glycoside is formed when hydroxyl group on anomeric carbon of sugar reacts with an amine. N-glycosidic linkage is present in nucleotides, RNA and DNA. So, nucleotides, RNA and DNA are examples for N-glycosides. Assignment: (c) Give examples of O- and N- glycosides 8/5/2024 24  Disaccharides They provide energy to human body. They consist of two monosaccharide units held together by glycosidic bond. So, they are glycosides. Most common disaccharides are maltose, lactose and sucrose. Oligosaccharides They consist of 2-10 monosaccharide units. The monosaccharides are joined together by glycoside bonds. Most important oligosaccharides are disaccharides. 8/5/2024 25  Disaccharides Maltose Structure It contains two glucose units. The anomeric carbon atom of first glucose and carbon atom 4 of the second glucose are involved in glycosidic linkage. The glycosidic linkage of maltose is symbolized as α (1→4). In this symbol, letter α-indicates the configuration of anomeric carbon atoms of both glucose units and numbers indicates carbon atoms involved in glycosidic linkage. Systematic name for maltose is O-α-D glucopyranosyl-(1→4)-α-D glucopyranose. Maltose is a reducing sugar because anomeric carbon of second glucose is free. Source for maltose Maltose is present in germinating cereals and in barley. Commercial malt sugar contains maltose. It may be formed during the hydrolysis of starch. 8/5/2024 26  Lactose Structure It contains one glucose and one galactose. The anomeric carbon atom of galactose and carbon atom 4 of glucose are involved in glycosidic linkage. It is symbolized as β (1→4). The systematic name for lactose is O-β-D galactopyranosyl-(1→4)-β-D-glucopyranose. Lactose is a reducing sugar because anomeric carbon of glucose is free. Source for lactose Lactose is synthesized in mammary gland and hence it occurs in milk. 8/5/2024 27 Sucrose Structure It contains glucose and fructose. The anomeric carbon of glucose and anomeric carbon of fructose are involved in glycosidic linkage. Further, glucose is in α-form whereas fructose is in β-form in sucrose. Hence the glycosidic linkage of sucrose is designated as α, β(1→2). Its systematic name is O-α-D-glucopyranosyl-(1→2)-β-D-fructofuranose. Sucrose is a non reducing sugar because both the functional groups of glucose and fructose are involved in glycosidic linkage. Source of sucrose Ripe fruit juices like pineapple, sugar cane, juice and honey are rich sources for sucrose. It also occurs in juices of sugar beets, carrot roots and sorghum. Invert sugar Sucrose has specific optical rotation of +66.5°. On hydrolysis, it changes to –19.8°. This change in optical rotation from dextro to levo when sucrose is hydrolysed is called as inversion. The hydrolysis mixture containing glucose and fructose is called as invert sugar. The change in optical rotation on hydrolysis is because of fructose which is more levo rotatory than dextro rotatory glucose. 8/5/2024 28 Other Disaccharides Isomaltose It contains two glucose units. Glycosidic linkage is α(1→6). Isomaltose is the disaccharide unit present in glycogen, amylopectin and dextran. Cellobiose It also contains two glucose units but they are joined in β(1→4) linkage. It is formed from cellulose. Trehalose It also contains two glucose units. The glycosidic linkage is α(1→1). So, it is a non-reducing disaccharide. It is a major sugar of insect hemo lymph. In fungi it serve as reserve food material. 8/5/2024 29  Other Oligosaccharides Beans and peas contain some oligosaccharides. These oligosaccharides contain 4 to 5 monosaccharide units. Stachyose and verbascose are a few such oligosaccharides. Usually these oligosaccharides are not utilized in human body. Oligosaccharide chains are also found in glycoproteins where they have important functions. Oligosaccharides are also important constituents of glycolipids present in cell membrane. 8/5/2024 30 Polysaccharides They are polymers of monosaccharides. They contain more than ten monosaccharide units. The monosaccharides are joined together by glycosidic linkage. Classification of Polysaccharides Polysaccharides are classified on the basis of the type of monosaccharide present. The two classes of polysaccharides are homo-polysaccharides and hetero-polysaccharides. (a) Homopolysaccharides They are entirely made up of one type of monosaccharides. On hydrolysis, they yield only one kind of monosaccharide. (b) Heteropolysaccharides They are made up of more than one type of monosaccharides. On hydrolysis they yield more than one type of monosaccharides. 8/5/2024 31 Homopolysaccharides Important homo-polysaccharides are starch, glycogen, cellulose, dextran and inulin and chitin. All these contain glucose as repeating unit. Other name for homo-polysaccharides are homo-glycans. Starch Structure It consist of two parts. A minor amylose component and a major amylopectin component. Amylose is a straight-chain polymer of glucose units; α(1→4) glycosidic linkage is present between glucose units. In contrast amylopectin is a branched molecule. In the linear portion of amylopectin (1→4) glycosidic linkage exist between glucose units whereas (1→6) glycosidic linkage exist at branch points between glucose residues. The branching occurs in amylopectin for every 2-30 glucose units. Amylose has helical coiled secondary structure and usually 6 glucose residue make one turn. Because of branching, secondary structure of amylopectin is a random coil structure. Function It is the major polysaccharide present in our food. It is also called storage polysaccharide because it serve as reserve food material in plants. It is present in food grains, tubers and roots like rice, wheat, potato and vegetables. 8/5/2024 32  Glycogen Structure The structure of glycogen is similar to that of amylopectin of starch. However, the number of branches in glycogen molecule is much more than amylopectin. There is one branch point for 6-7 glucose residues. Function It is the major storage polysaccharide (carbohydrate) in human body. It is mainly present in liver and muscle. It is also called as animal starch. 8/5/2024 33  Cellulose Structure It has linear chain of glucose residues, which are linked by β(1→4) glycosidic linkage. It occurs as bundle of fibres in nature. The linear chains are arranged side by side and hydrogen bonding between adjacent stands stabilizes the structure. Function It is the most abundant polysaccharide in nature. It is found in fibrous parts of plants like wood, cotton and straw. 8/5/2024 34  Dextran Structure It has structure similar to amylopectin. In the linear part, glucose units are linked by α(1→6) glycosidic bond and α(1→3) glycosidic linkage is present between glucose unit at branch points. Function It is polysaccharide present in bacteria. Medical importance To maintain plasma volume dextran is used in clinical medicine. Dental plaque is due to dextran synthesized from sucrose by oral bacteria and insects. 8/5/2024 35  Inulin Structure It is a polysaccharide composed of fructose. β(1→2) glycosidic linkage is present between fructose units. Function It is present in tubers of chicory, dhalia and in the bulb of onion and garlic. Inulin is used to determine glomerular filtration of kidney. Chitin Structure A polysaccharide composed of N-acetyl glucosamine. Glycosidic linkage is β(1→4). Function It is an important structural polysaccharide of invertebrates like crabs, lobster 8/5/2024 36  Heteropolysaccharides They are also called as mucopolysaccharides or glycosaminoglycans. Mucopolysaccharides consist of repeating disaccharide units. The disaccharide consist of two types monosaccharides. The mucopolysaccharides are component of connective tissue. Hence, they are often referred as structural polysaccharides. The mucopolysaccharides are also found in mucous secretions. The mucopolysaccharides combines with proteins like collagen and elastin and forms extracellular medium or ground substance of connective tissue. Mucopolysaccharides are also components of extracellular matrix of bone, cartilage and tendons. The complex of mucopolysaccharide and protein is called as proteoglycan. Mucopolysaccharides also function as lubricants and shock absorbers. 8/5/2024 37 Few important mucopolysaccharides or glycosaminoglycans (GAGs) are: Hyaluronic Acid (HA) Structure The repeating disaccharide of hyaluronic acid consist of glucuronic acid and N- acetylglucosamine. Functions 1. It is present in synovial fluid and function as lubricant. 2. It is also present in skin, loose connective tissue, umbilical cord and ovum. 3. It is present in vitreous body of eye. 8/5/2024 38 Medical importance 1. As the age advances hyaluronic acid is replaced by-dermatan sulfate in synovial fluid. Dermatan sulfate is not a good lubricant, hence age related pains develop in old people. 2. In young people, vitreous is clear elastic gel in which hyaluronic acid is associated with collagen. As the age advances the elasticity of vitreous is reduced due to decreased association between collagen and hyaluronic acid. As a result, vision is affected in older people. 3. Hyaluronic acid of tumour cells has role in migration of these cells. 4. Hyaluronic acid is involved in wound healing (repair). In the initial phase of wound healing (repair), hyaluronic acid concentration increases many fold at the wound site. It allows rapid migration of the cells to the site of connective tissue development. 5. Hyaluronic acid helps in scarless repair. If suitable levels of HA are maintained during would healing scar formation is reduced or even prevented. 6. HA content of skin decreases as age advances this is the reason for increased susceptibility of aged people for scar formation. 7. Pneumonia, meningitis and bacteremia causing pathogenic bacteria contains hyaluronte lyase. Hydrolysis of HA by this enzyme facilitates invasion of host by these bacteria. 8/5/2024 39 Chondroitin sulfate A and B chondroitin-4-sulfate and chondroitin-6-sulfate Structure 1. The repeating disaccharide unit of chondroitin sulfates consist of glucuronic acid and N-acetyl galactosamine. N-acetyl galactosamine is sulfated. 2. In chondroitin-4-sulfate, 4th carbon atom of N-acetyl galactosamine is sulfated where as in chondroitin-6-sulfate the 6th carbon is sulfated. Functions 1. Chondroitin sulfates are components of cartilage, bone and tendons. 2. They are also present in the cornea and retina of the eye. 3. Chondroitin sulfate content decreases in cartilage as age advances. 8/5/2024 40  Heparin Structure 1. The repeating disaccharide unit of heparin consist of glucosamine and either iduronic acid or glucuronic acid. 2. Majority of uronic acids are iduronic acids. Further amino groups of glucosamine is sulfated. Functions 1. Heparin is a normal anti-coagulant present blood. 2. It is produced by mast cells present in the arteries, liver, lung and skin. 3. Unlike other glycosaminoglycans, heparin is an intracellular component. 8/5/2024 41  Dermatan Sulfate Structure The repeating disaccharide consist of Iduronic acid and N- acetyl galactosamine sulfate. Functions It is present in skin, cornea and bone. It has a role in corneal transparency maintenance. 8/5/2024 42  Keratan sulfates I and II Structure 1. The repeating disaccharide consist of galactose and N-acetyl glucosamine sulfate. 2. Type I and II have different attachments to protein. Functions 1. They are components of cartilage, cornea and loose connective tissue. 2. Keratan sulfate l is important for corneal transparency. 8/5/2024 43 Glycoproteins They are found in mucous fluids, tissues, blood and in cell membrane. They are proteins containing short chains of carbohydrates. The carbohydrate chains are usually oligosaccharides. These oligosaccharide chains are attached to proteins by O-glycosidic and N-glycosidic bonds. Further oligosaccharide is composed of fucose, N-acetyl glucosamine, galactose and glucose. The oligosaccharide chains have important functions like: 1. Oligosaccharide present on the surface of erythrocytes are responsible for the classification of blood groups. They determine blood group and hence they are called as blood group substances. 2. Oligosaccharides determine the life span of proteins. 3. Cell-cell recognition depends on oligosaccharide chains of glycoproteins. 4. Glycoproteins of some invertebrates function as antifreezing agents. They are known as antifreeze glycoproteins (AFGPs). One such glycoprotein is identified in Antarctic fishes. 5. It is very essential for their survival in such sub zero environment that exist at Antarctica. 6, It is present in the blood of the Antarctic fishes. It prevents freezing by binding to ice, which enables these fishes to survive in the surrounding icy environment. It is surprising that this protein arose from pancreatic trypsinogen like protease. 8/5/2024 44  Sialic Acids Structure 1. Sialic acids are acyl derivatives of neuraminic acid. 2. Neuraminic acid is a 9 carbon sugar consisting of mannosamine and pyruvate. Usually amino group of mannosamine of neuraminic acid is acetylated. Hence, N-acetyl neuraminic acid (NANA) is an example for sialic acid. Functions 1. Oligosaccharides of some membrane glycoproteins contains a terminal sialic acid. 2. Sialic acid is an important constituent of glycolipids present in cell membrane and nervous tissue. 8/5/2024 45  Reference & Review: Rao NM (2006). Medical Biochemistry: Rao NM (2nd ed.). New Delhi: New Age International (P) Ltd., Publishers. 8/5/2024 46