Carbohydrate Chemistry PDF

Carbohydrate Chemistry Dr. Maghawry Hegazy(Ph.D.) Lecturer of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Cairo, Al-Azhar University 1  Outlines of lecture 1....

Carbohydrate Chemistry Dr. Maghawry Hegazy(Ph.D.) Lecturer of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Cairo, Al-Azhar University 1  Outlines of lecture 1. Definition of carbohydrates 2. Importance of carbohydrates 3. Classification of carbohydrates 4. Monosaccharides 5. Asymmetric carbon atom (chiral carbon) 6. Optical activity and optical isomerism 7. Enantiomers and Epimers 8. Anomeric carbon and Anomers 9. Haworth projection formula of sugars 10. Sugar Derivatives 11. Disaccharides 12. Glycosidic bond and glycosides 13. Polysaccharides (Homopolysaccharides and Heteropolysaccharides) 14. Glycosaminoglycans (GAGs) 15. Examples and function of GAGS 2  Carbohydrates ✓Carbohydrates are polyhydroxy aldehyde or ketone or any substances derived from them or any compound that yield these derivatives on hydrolysis. 3  Carbohydrates ✓Carbohydrate means carbon and water (C + H2O)(CHO). ✓For every carbon there is 1 water molecule or 2 hydrogen atoms and 1 oxygen atom. Also, They are called saccharides. 4 ❑ Importance of carbohydrates ❖ CHO are widely distributed in plants and animals. ❖ CHO constitute about 60% of our diet. ✓ They are important because 1. They serve as a source of energy as glucose. 2. CHO may combine with lipids (glycolipids) or protein (glycoproteins), both enter in the structure of the cell membrane. 3. They form structural elements in animal and plant cell. *** The suffix – ose means sugar. 5  Classification of carbohydrates They are classified according to the number of sugar units into: CHO Monosaccharides Disaccharides Oligosaccharides Polysaccharides 1 3 -10 More than 10 6  Monosaccharides ✓ They are the simplest units of carbohydrates. ✓ On hydrolysis, they can not give a simpler form. ✓ The general formula is Cn(H2O)n. ✓ They are Aldoses (containing an aldehyde group usually at C1) or Ketoses (containing a ketone group, usually at C2). 7  Nomenclature of monosaccharides 1. According to the presence of aldehyde or ketone group: a) Aldoses: monosaccharides containing aldehyde group (-CHO). b) Ketoses: monosaccharides containing ketone group (-C=O). 2. According to the number of carbon atoms: a) Trioses: monosaccharides containing 3 carbons. b) Tetroses: monosaccharides containing 4 carbons. c) Pentoses: monosaccharides containing 5 carbons. d) Hexoses: monosaccharides containing 6 carbons. e) Heptoses: monosaccharides containing 7 carbons. 8  Nomenclature of monosaccharides 3. According to both presence of aldehyde or ketone groups and number of carbon atoms: a) Aldotrioses and ketotrioses. b) Aldotetroses and ketotetroses. c) Aldopentoses and ketopentoses. d) Aldohexoses and ketohexoses. 9  Classification of monosaccharides 1- Trioses: monosaccharides containing 3 carbon atoms. They may be: a- Aldotrioses such as glyceraldehyde (glycerose). b- Ketotrioses such as dihydroxyacetone. 10  Classification of monosaccharides 2- Tetroses: monosaccharides containing 4 carbon atoms, they may be: a- Aldotetroses such as erythrose. b- Ketotetroses such as erythrulose. (N.B.: The suffix – ulose means keto sugar). 11  Classification of monosaccharides 3- Pentoses: monosaccharides containing 5 carbon atoms, they may be a- Aldopentoses such as Ribose, Arabinose, Xylose & Lyxose. b- Ketotpentoses such as Ribulose and Xylulose. 12  Importance of pentoses 1) Ribose and deoxyribose enter in the structure of nucleic acids RNA and DNA. 2) Ribose enters in the structure of high energy phosphate compounds (ATP, GTP). 3) Ribose enters in the structure of coenzymes NAD, NADP and flavoproteins. 4) Arabinose and xylose are constituents of glycoprotein in plant and animal cell. 5) Lyxose is a constituent of lyxoflavin isolated from human heart muscle. 13  Classification of monosaccharides 4- Hexoses: monosaccharides containing 6 carbon atoms and may be a- Aldohexoses such as glucose, galactose and mannose. b- Ketohexoses such as fructose. 14  Importance of hexoses 1) Glucose is the major source of energy in mammals. ✓ Glucose is the most important sugar of carbohydrate. ✓ Glucose is the main sugar in blood. ✓ In the liver and other tissues, it is converted to all carbohydrates in the body e.g. glycogen, galactose, ribose and fructose. 2) Fructose (Fruit sugar): It is the main sugar of semen. 3) Galactose: It is essential for synthesis of lactose in lactating mammary glands to make milk sugar (lactose). 4) Mannose: a constituent of many glycoproteins. 15  Classification of monosaccharides 5- Heptoses: monosaccharides containing 7 carbon atoms such as sedoheptulose which is formed in Hexose monophosphate shunt. 16  Asymmetric carbon atom (chiral carbon) ✓ It is the carbon atom which attached to 4 different groups or atoms. 17  Asymmetric carbon atom (chiral carbon) ✓ Any substances containing one or more asymmetric carbon atom shows two properties; 1. Optical activity 2. Optical isomerism 18 A. Optical activity: is the ability of substance to rotate plane polarized light either to the right or to the left. ✓Polarized light: Light that is reflected or transmitted through certain media so that all vibrations are restricted to a single plane. ✓If the substance rotate plane polarized light to: (a) The right, so it is called dextrorotatory or (d) or (+). (b) Or to the left, so it is called levorotatory or (l) or (-). 19 ✓Glucose contains 4 asymmetric carbon atoms and it is dextrorotatory, so it is sometimes named dextrose. ✓Fructose contain 3 asymmetric carbon atom and it is levorotatory, so it is sometimes named levulose. 20 B. Optical isomerism: ✓ It is the ability of substances to present in more than one form (isomer). ✓A substance containing one asymmetric carbon atom has 2 isomers. ✓ A substance containing 2 or more asymmetric carbon atoms can exist n in a number of isomers =(2 ). where n = the number of asymmetric carbon atoms. e.g. glucose has 4 asymmetric carbon atoms, so, the number of isomers 4 are 2 =16. 21 22 1) Enantiomers: ✓ They are two stereoisomers that are mirror images of each other and non- superimposable (not identical). ✓ They are classified into D & L forms according to the position of –OH group attached to the carbon atom adjacent to the last –CH2OH (i.e.; carbon atom number 5 in glucose). ▪ (D) form in which -OH group attached to asymmetric carbon atom is on the right side. ▪ (L) form in which -OH group attached to asymmetric carbon atom is on the left side. 23 24 25 ✓ The simplest carbohydrate is glyceraldehyde that has one asymmetric carbon atom. ✓ The glyceraldehyde is the reference sugar which may be present in: (D) form in which -OH group attached to asymmetric carbon atom is on the right side. (L) form in which -OH group attached to asymmetric carbon atom is on the left side. ✓All other monosaccharides are considered to be derived from glyceraldehyde. ✓Most of the monosaccharides occurring in mammals are of D-form. However, a sugar may be dextrorotatory (d) or levorotatory (l) irrespective of its D or L forms. 26 27  Specific rotation: It is the angle of rotation specific for each optically active substance when: a) The concentration of substance is 100 g/dl. b) The length of measuring tube is 10 cm e.g. specific rotation for glucose is (+52.5°) and for fructose is (-91°). Racemic mixture or (Racemate) (Racemization): It is the mixture containing equal number of molecules of two optically active sugars or two enantiomers, or substances that have dissymmetric molecular structures that are mirror images of one another; one is dextrorotatory (d) and the other is levorotatory (l). Thus, it shows no optical activity. Resolution: It is the separation of optically inactive racemic mixture into its optically active substances. Or it is the method when a racemic modification is divided into its constituent enantiomers. 28 2) Epimeric carbon and epimers a) Epimeric carbon: is the asymmetric carbon atom other than carbon of aldehyde or ketone group e.g. carbons number 2,3 and 4 of glucose. b) Epimers: are isomers resulting from the change of position of groups around the epimeric carbons. Glucose, galactose and mannose are epimers. They are sugar molecules that differ in configuration at only one of chiral centers. 1) Glucose has 3 epimeric carbons 2, 3 and 4. 2) Galactose: epimer of carbon 4 of glucose. 3) Mannose: epimer of carbon 2 of glucose. 4) D-mannose and D-galactose are NOT epimers. 29 3) Aldose-ketose isomerism (functional group isomerism) ✓Fructose has the same molecular formula as glucose but differs in structure formula (functional group). One contains keto group and the other contains an aldehyde group. Both are isomers. 30 31 4. Pyranose and furanose a) The 1-5 ring form is called pyranose (six-membered ring) as it resembles an organic compound called pyran e.g. α and β glucopyranose. b) The 1-4 ring form is called furanose (five-membered ring) as It resembles an organic compound called furan e.g. α and β glucofuranose. 32  Ring (cyclic) structure of sugars The simple open chain formula of sugars falls to explain some reactions e.g. glucose, which has aldehyde group, does not give all the reactions of aldehyde. This indicates that the CHO group must be masked or combined in some way. In solution, the sugar which has an aldehyde group undergoes the following: 1. Hydration of aldehyde group to form aldenol group (alcohol). 2. Intra-molecular reactions occur by subsequent condensation between one of the - OH of aldenol group and the -OH group of C 4 or C5 to form ring structure (hemiacetal structure). Here, the carbonyl group becomes asymmetric carbon atom (anomeric carbon). 3. (a) If the remaining -OH is on the right side, it is α -sugar. (b) If the remaining -OH is on the left side, it is β- sugar. 33 34  Haworth and chair forms a) Cyclic structure of sugars may be present in the form of Haworth or chair forms. In which, the arrangement of H and -OH groups around carbon atoms is as follows: 1) All the -OH groups on the right side in old ring structure are written downwards in Haworth formula. 2) All the -OH groups on the left side in old ring structure are written upwards in Haworth formula. 3) These rules are reversed at CH2OH groups e.g. last carbon atom of glucose that attached to oxygen i.e. C4 in furanose and C5 in pyranose. 35 36 4) Anomers ✓Anomeric carbon: is the new asymmetric carbon atom obtained from active carbonyl group of sugar; carbon number 1 in aldoses and carbon number 2 in ketoses. ✓Anomers: These are isomers obtained from the change of position of hydroxyl group attached to the anomeric carbon e.g.; α and β glucose are 2 anomers. ✓α- form in which the –OH group attached to anomeric carbon is at right side while β- form it is at left side. 37  Sugar derivatives A- Sugar acids (Oxidation product): These are produced by oxidation of carbonyl carbon, last hydroxyl carbon or both. 1- Aldonic acids: Oxidation of carbonyl carbon (C1 in glucose) to carboxylic group gives aldonic acid e.g.; glucose is oxidized into gluconic acid. 2- Uronic acid: Oxidation of last hydroxyl carbon (C6 in glucose) will give uronic acid e.g.; glucose is oxidized into glucuronic acid. 3- Aldaric acid: These are dicarboxylic acids produced by oxidation of both carbonyl group and last hydroxyl group (C1 and C6 in glucose) into carboxylic group e.g. glucose will be oxidized to glucaric acid. 38 B- Sugar alcohols (Reduction product): monosaccharides, both aldoses and ketoses may be reduced at carbonyl carbon to the corresponding alcohols. 1) Glucose is reduced to sorbitol (glucitol), galactose is reduced to galacticol (dulcitol), mannose is reduced to mannitol. 2) Fructose is reduced to mannitol and sorbitol. 3) Ribose is reduced to ribitol, a constituent of vitamin B2 (riboflavin) and coenzyme FAD. 39 C- Deoxy sugars: 1. Are sugars in which one of the hydroxyl groups has been replaced by hydrogen atom i.e. one oxygen is missed. 2. Deoxyribose which occurs in nucleic acid DNA. 3. L-Fucose (6-deoxygalactose): occurring in glycoproteins. 40 D- Amino sugars: in these sugars, the hydroxyl group attached to carbon number 2 is replaced by an amino or an acetylamino group. They are found in many oligosaccharides and polysaccharides. 1. Amino sugars are constituents of glycoproteins and GAGS. 2. Examples: a) Glucosamine: It occurs in heparin and hyaluronic acid. b) Galactosamine: It occurs in chondroitin sulphate. c) Mannosamine: It occurs in neuraminic acid and sialic acids. 41 E- Amino sugar acids: 1. These are a condensation of amino sugars and some acids. 2. They are occurring in glycoproteins. 3. Examples include neuraminic acid (NANA) and sialic acid which is N- acetyl neuraminic acid. 42  Glycosidic bond and glycosides A. Glycosidic bond: It is the bond between a carbohydrate and another compound to form a complex carbohydrate. 1. This bond between the hydroxyl group of anomeric carbon of monosaccharide (carbon 1 in aldoses or carbon 2 in ketoses) and another compound which may be: a) Another monosaccharide to form disaccharide as sucrose. b) Aglycone i.e. non-carbohydrate to form glycoside. 43  Glycosidic bond and glycosides The glycosidic bond is mostly unstable and susceptible to hydrolysis (by diluted acids or by enzymes, e.g., β-glucosidases). Accordingly, the types of glycosidic linkages are classified as: 1. O-glycosides (if the glycosidic bond is via oxygen); the most abundant form in plants. 2. C-glycosides (linkage via a carbon); this type of linkage is resistant to hydrolysis. 3. S-glycosides (linkage via a sulfur; aglycone must have —SH group) present in glucosinolates (thioglycosides). 4. N-glycosides (linkage via a nitrogen; aglycone must have —NH group) present in nucleosides. ✓ All sugar-sugar glycosidic bonds are O type linkage. 44  Disaccharides These are formed by condensation of 2 molecules of monosaccharides bounded together by glycosidic bond. Its general formula is Cn (H2O)n-1. The most important disaccharides are: 1- Maltose (2 α-glucose molecules linked by α 1-4 glycosidic bond) 2- Isomaltose (2 α-glucose molecules linked by α 1-6 glycosidic bond) 3- Cellobiose (2β- glucose + β-glucose linked by β 1 – 4 glycosidic bond) 4- Lactose (β- glucose + β-galactose linked by β 1 – 4 glycosidic bond) 5- Sucrose (α-glucose + β- Fructose linked by α1 –β2 glycosidic bond) 6. Trehalose (α- glucose + α-glucose linked by α 1 - 1 glycosidic bond) 45  1- Maltose (Malt sugar) Structure It is formed of 2 α-glucose molecules (2 molecules of α-D glucopyranose) linked by α 1-4 glycosidic bond. Source Malt, in addition it is produced during digestion of starch by amylase enzyme. Properties Maltose containing free carbonyl (aldehyde) group, so it is reducing sugar. 46  2- Isomaltose Structure It is formed of 2 α-glucose molecules (2 molecules of α-D glucopyranose) linked by α 1-6 glycosidic bond. Source It is produced during digestion of starch and glycogen by amylase enzyme. Properties It containing free carbonyl (aldehyde) group, so it is reducing sugar. 47  3- Cellobiose Structure It is formed of 2 β-glucose units (2 units of β-D glucopyranose) linked together by β 1-4 glycosidic bond. Source It is obtained by partial hydrolysis of cellulose present in plant. Properties It containing free carbonyl (aldehyde) group, so it is reducing sugar. 48  4- Lactose (milk sugar) Structure It is formed of β- glucose + β-galactose (2 molecules of β-D- galactopyranose and β-D glucopyranose) linked by β 1 – 4 glycosidic bond. Source ✓ It is the sugar present in milk. ✓It is digested by intestinal enzyme called: lactase into galactose and glucose. ✓Deficiency of this enzyme stops the digestion of lactose. This leads to its fermentation by intestinal bacteria, diarrhea and abdominal distension. Properties Lactose contains free carbonyl group, so it is reducing sugar. 49  5- Sucrose Structure It is formed of α-glucose + β-Fructose (2 molecules of α –D glucopyranose and β-D Fructofuranose) linked together by α1 –β2 glycosidic bond. Source It is present in sugar cane, beet sugar, pineapple and carrot. Properties Sucrose contain no free carbonyl group (because both anomeric carbons are involved in glycosidic bond), so it is non reducing sugar. It cannot be present in α and β forms. Sucrose is dextrorotatory. On hydrolysis by invertase (sucrase) enzyme, it gives a mixture of equal number of glucose and fructose molecules. This mixture is called invert sugar and it is levorotatory. 50  6- Trehalose Structure It is formed of 2 α –D glucopyranose linked together by α 1-1 glycosidic bond. Source It is present in fungi and yeast. Properties It contain no free carbonyl group, so it is non reducing sugar. It cannot be present in α and β forms. It can be used as a sweetener and preservative for foods 51 Invert Sugar Structure: It is a sugar that contains equal number of both glucose and fructose molecules (unbound). Sources a) Bee honey b) By hydrolysis of sucrose by sucrase (invertase) enzyme. Properties It contains free carbonyl groups, so it is reducing sugar and can be present in α and β forms. 52 Why is sucrose called 'invert sugar’? On hydrolysis, sucrose give glucose and fructose in 1:1. due to the presence of optical isomers of mixture of glucose and fructose sugar, the angle of specific rotation of plain polarized light changes from positive to a negative value. 1. The glucose and fructose units are joined by an acetal oxygen bridge in the alpha-1 on the glucose and beta-2 on the fructose orientation. 2. Sucrose is dextrorotatory (+66.6) in nature and on hydrolysis it gives dextrorotatory glucose and levorotatory fructose. 3. Levorotation of fructose is (-91) degree whereas dextrorotation of glucose is (+52.5) degree. As, levorotation is much more than dextrorotation, hence, solution is levorotatory in nature. 4. Hydrolysis of sucrose brings about a change in the sign of rotation from dextro(+) to levo(-) and product is known as invert sugar. 53  Hydrolysis of sucrose 54  Polysaccharides These are carbohydrates formed of more than 10 monosaccharides units linked by glycosidic linkages. They are classified into: A-Homopolysaccharides which are composed of one type of monosaccharides such as glycogen. They contain repeated same sugar units and include: starch, dextrin, glycogen, cellulose, dextran and inulin. B-Heteropolysaccharides which are made of different types of monosaccharides units such as mucopolysaccharides They contain repeated different sugar units and include GAGS. 55 A- Homopolysaccharides They include: 1- Starch (glucosan or glucan) Structure: starch granule is formed of inner and outer layers. Inner layer called amylose which constitutes 15 – 20 % of starch and formed of non branching structure of glucose units linked together by α 1-4 glycosidic bonds. Functions: starch is the main carbohydrate content in our diet. It constitutes about 60% of our daily ingested food. Starch is the storage form of carbohydrate in plant. 56  Outer layer called amylopectin which constitute 80 – 85 % of the granule and formed of branched chains. Each chain is composed of 24 – 30 glucose units linked together by α 1-4 glycosidic bonds and α 1-6 glycosidic bond at the branching point. 57 2- Glycogen (Animal starch) Structure: It is highly branched chain homopolysaccharides. Each branch is composed of 12 – 14 glucose units, linked together by α 1-4 glycosidic bonds and by α 1-6 glycosidic bond at branching point. Properties: It is the storage form of carbohydrates in human and animals. It is synthesized and stored in liver, muscles. Functions of glycogen: 1) Liver glycogen: It maintains normal blood glucose concentration especially during the early stage of fast (between meals). After 12-18 hours fasting, liver glycogen is depleted. 2) Muscle glycogen: It acts as a source of energy within the muscle itself especially during muscle contractions. 58 3- Cellulose It is the major form of structural carbohydrates in plants. Structure: It is long straight nonbranching polymer of β-D-glucopyranose linked together by β 1-4 glycosidic linkage. Cellulose in diet cannot be digested by many mammals including humans due to absence of hydrolase enzymes that can attack β-linkage. Functions: Its presence in diet is important, because it cannot be digested, so it will increase the bulk of stool and stimulate the intestinal movement and prevent constipation. 59 4- Inulin (Fructosan) Structure: formed of repeated units of fructose linked together by β 1-2 bonds. Sources: Root of artichokes. Medical importance: Inulin clearance is one of diagnostic tests for investigation of glomerular filtration rate (GFR). 60 Heteropolysaccharides They are made of 2 or more different types of monosaccharides units. They include glycosaminoglycans, proteoglycans and glycoproteins. Glycosaminoglycans (GAGs) (known as mucopolysaccharides) are long unbranched polysaccharides containing a repeating disaccharide units. Proteoglycan These are chains of GAGS attached to protein molecules. The carbohydrate part is present in very long unbranched chains (more than 50 monosaccharide molecules) attached to protein core. Glycoprotein It consists of protein core and short branched chain of carbohydrate (2 – 15 monosaccharide units), usually called oligosaccharide chain. 61  Glycoproteins have a higher protein content by mass, being typically 50%+ of the total mass. Proteoglycans have a much higher carbohydrate content, with carbohydrates comprising typically 95%+ of the total mass. There is no difference; the two terms are simply different terms for the same type of biomolecule. 62 Glycosaminoglycans (GAGs) ✓ Formed of long unbranched repeating disaccharide units (acidic sugar-amino sugar)n a) The acidic sugar is either D-glucuronic acid or its epimer, L- iduronic acid. b) The amino sugar is either D-glucosamine or D-galactosamine in which the amino group is usually acetylated. The amino sugar of GAGS may also be sulfated at carbon 4 or 6. ✓ The uronic acid and sulfate residues cause them to be very negatively charged. ✓GAGS act as lubricants and cushion for other tissues because they have the property of holding large quantities of water. 63 64 65 There are 5 major classes of GAGs (1) Hyaluronic acid (2) Chondroitin sulphate (3) Dermatan sulphate (4) Keratan sulphate (5) Heparin 66 ✓ GAGs Name of GAGS Structure Site Function Repeating unit 1) Glucuronic acid Cartilage o Lubricant in joints Synovial fluid o Makes cartilage 2) N-acetylglucosamine Vitreous humor of compressible 1. Hyaluronic acid the eye o Cell migration during N.B. It is the only GAGs wound repair which contain no sulphate group 1) Glucuronic acid. The most abundant o In cartilage: it binds GAGs in the body it is collagen 2) N-acetylgalactosamine 2. Chondroitin found in: o Makes cartilage with sulfate on either C4 or sulfate Cartilage and bones compressible C6 Aorta, skin and o Maintain the shape umbilical cord of skeletal system 1) L-iduronic acid Cornea o Important role in Sclera corneal transparency 2) N- acetylgalactosamine 3. Dermatan o In sclera may play a with sulfate on C4 sulphate role In maintaining the overall shape of the eye 67 ✓ GAGs Name of GAGS Structure Site Function Repeating unit 1) Galactose (no uronic acid) Cornea o Important role in 4. Keratan sulfate Cartilage corneal 2) N-acetylglucosamine with transparency sulfate on C6 1) L-Iduronic acid with Mast cells o Heparin acts as sulfate on C2 which are anticoagulant 2) Glucosamine with sulfate located along o Heparan sulfate acts 5. Heparin on C2 and C6 the wall of as cell membrane It is the only intracellular blood vessels receptors GAGS of liver, lungs, o It participates in cell heart, kidney adhesion and cell- and spleen cell interaction o It plays a role in the glomerular filtration 68