Pharmaceutical Biochemistry II (Theory) PDF

Pharmaceutical Biochemistry II (Theory) Carbohydrate Carbohydrates are the polyhydroxy aldehyde or ketone compounds. Carbohydrates are also called as “saccharides” and this word is derived from Greek word “saccharo” which means “sugar”. Another definition of carbohydrate is that they are polyhydrox...

Pharmaceutical Biochemistry II (Theory) Carbohydrate Carbohydrates are the polyhydroxy aldehyde or ketone compounds. Carbohydrates are also called as “saccharides” and this word is derived from Greek word “saccharo” which means “sugar”. Another definition of carbohydrate is that they are polyhydroxylated compounds with at least 3 Carbon atoms with potentially active carbonyl group which may be either aldehyde or ketone. Carbohydrates also include those substances that yield such compounds upon hydrolysis. Some carbohydrates also contain N, P and S. The name “carbohydrate” is derived from the fact that the first compounds of this group studied had an empirical formula C x(H2O)y (hydrates of carbon). Now it is known that many carbohydrates do not fit into this formula e.g. deoxyribose which is C 5H10O4. However, when carbohydrates are heated then carbon and water are obtained. Carbohydrates are the most abundant biomolecules on the earth. They form only 2% of human body mass. They are source of about 80% of human caloric intake. Each year, photosynthesis converts more than 100 billion metric tons of CO2 and H2O into cellulose and other plant products. These carbohydrate products have important structural and metabolic role. In plants, glucose is synthesized from carbon dioxide and water by photosynthesis and stored as starch or used to synthesize the cellulose of the plant cell walls. Animals can synthesize carbohydrates from amino acids, but in most animal carbohydrate is derived ultimately from plants source. Mostly, dietary carbohydrate is absorbed into the bloodstream as glucose while other sugars that are absorbed are converted to glucose in the liver. Glucose is most important among all carbohydrates. Glucose is the precursor for synthesis of all the other carbohydrates in the body including glycogen for storage; ribose and deoxyribose for nucleic acids; galactose for lactose of milk, glycolipids and glycoproteins of the body. Diseases associated with carbohydrate metabolism include diabetes mellitus, galactosemia, glycogen storage diseases, and lactose intolerance. Blood glucose is serving as direct food for brain. Mammary glands take the glucose from the blood convert it into the galactose. Mammary glands combine this galactose with glucose to form the lactose. Glucose is oxidized preferably by all tissues of the body to provide energy. More than half of oral energy of the body is provided by glucose. Excess of glucose is readily converted into fats and stored in the fat depots. Dr. KASHIF KHAN (IPS_UVAS) Page 1  Pharmaceutical Biochemistry II (Theory) Classification There is no single satisfactory classification of carbohydrates. Commonly used classification is given below; 1. Monosaccharides: These are simple sugars which cannot be further hydrolyzed and have the empirical formula (CH2O)n where n = 3 or greater. They may be classified as trioses, tetroses, pentoses, hexoses, or heptoses, depending upon the number of carbon atoms. They are either aldoses (contain aldehyde group) or ketoses (contain ketone group). Examples No. of Carbons Generic Name Aldoses Ketoses 3 Trioses Glyceraldehyde Dihydroxyacetone 4 Tetroses Erythrose Erythrulose 5 Pentoses Ribose Ribulose 6 Hexoses Glucose Fructose 7 Heptoses Glucoheptose Seduheptulose In nomenclature of carbohydrates, the type of carbonyl group (aldehyde or ketone) and the generic name are combined to give the name to the monosaccharides. For example, glucose is an aldose as well as a hexose; it is therefore, an aldohexose while fructose is a ketohexose. Monosaccharides are white crystalline solids, freely soluble in water and most have a sweet taste. Dr. KASHIF KHAN (IPS_UVAS) Page 2  Pharmaceutical Biochemistry II (Theory) Dr. KASHIF KHAN (IPS_UVAS) Page 3  Pharmaceutical Biochemistry II (Theory) 2. Disaccharides: Disaccharides are the condensation product of two monosaccharide units linked together by a covalent bond e.g., maltose (2 glucose molecules), sucrose (1 glucose + 1 fructose), lactose (1 glucose + 1 galactose). Monosaccharides are joined together by glycosidic linkage. 3. Oligosaccharides: The word oligosaccharide is derived from the Greek word “oligo” which means “few”. These are the condensation product of 3 to 10 monosaccharide units. Sometime disaccharides are also included in this group. The monosaccharides are joined together through glycosidic linkages. Examples include maltotriose (3 glucose molecules), α-dextrin (8 glucose molecules). 4. Polysaccharides: Polysaccharides are the condensation product of more than ten monosaccharides units. They may be in straight chain or in branches (e.g. cellulose, glycogen, starch, and dextrin). There are two types of polysaccharides. a. Homopolysaccharides: These are polysaccharides, formed from combination of only one type of monosaccharide units. They are also called homoglycans. Examples include starch, glycogen, cellulose and dextrins. All of which yield glucose on hydrolysis. b. Heteropolysaccharides: These are the polysaccharides, formed from combination of two or more types of monosaccharides units. They are also called as heteroglycans. These are divided into following three groups. i. Mucopolysaccharides: These polysaccharides, in addition to containing carbohydrate group also contain acid group e.g. hyaluronic acid, heparin, blood groups polysaccharides, serum mucoids. ii. Mucilages: These polysaccharides occur in plants e.g. agar, vegetable gums and pectin iii. Hemicellulose: These polysaccharides occur in plants e.g. hemicellulose. 5. Derived Carbohydrates: These carbohydrates are derived from carbohydrates by various chemical reactions. These may be: Dr. KASHIF KHAN (IPS_UVAS) Page 4  Pharmaceutical Biochemistry II (Theory) a. Oxidation products: These sugar acids derived from glucose on its oxidation e.g., gluconic acid, glucuronic acid, glucaric acid, Ascorbic acid (vitamin C). b. Reduction products: These are the reduced products of carbohydrates. These are polyhydroxy alcohols e.g., glycerol (derived from glyceraldehydes), ribitol (derived from ribose). c. Amino sugars: These have –NH2 group at carbon No.2 e.g., glucosamine, galactosamine, mannosamine. d. Deoxy sugars: These have less number of oxygen atoms than other sugars e.g., deoxyribose (present in DNA and is one oxygen atom lesser than ribose). Carbohydrates also present in combination with lipids (glycolipids) and proteins (glycoproteins). Isomerism in carbohydrates Stereoisomerism The word isomer is derived from the Greek words “isos” meaning "equal" and “meros” meaning "part". Isomers are compounds with the same molecular formula but different structural formula e.g. glucose, fructose, mannose and galactose has same molecular formulas i.e. C6H12O6 but different structural formulas. The isomerism which based on the difference in the arrangement of the atoms in the space is called stereoisomerism. H C O CH2OH H C O H C O H C OH C O H C OH H C OH HO C H HO C H HO C H HO C H H C OH H C OH HO C H H C OH H C OH H C OH H C OH H C OH CH2OH CH2OH CH2OH CH2OH Glucose Fructose Galactose Glucose Dr. KASHIF KHAN (IPS_UVAS) Page 5  Pharmaceutical Biochemistry II (Theory) Epimers The stereoisomers that differ in configuration around one specific carbon atom (optically active carbon atom) other than carbonyl carbon are called epimers e.g. glucose and galactose differ from each other only in the position of –OH at Carbon No. 4. Similarly, glucose and mannose are different from each other only in the position of –OH at Carbon No 2. So, both are epimers of each other. Anomers The stereoisomers that differ from each other in configuration around carbonyl carbon only are called anomers. When a monosaccharides cyclizes, its anomeric carbon also becomes asymmetric with two possible forms of their configurations i.e. α and β forms. Such stereoisomers that differ in configuration at the anomeric carbon atom i.e. carbon no 1 in aldoses (e.g. glucopyranose) or carbon no 2 in ketoses (e.g. fructofuranose) are called anomers. e.g. α-D-glucopyranose and β-D-Glucopyranose. Both anomers have different physical and chemical properties. Both α and β anomers are interconvertable in aqueous solution. The process of inter-conversion of as α and β anomers is called mutarotation. Phenomenon of mutarotation is increase with increase in number of OH groups. Other example is α-D-fructofuranose and β-D-fructofuranose. Dr. KASHIF KHAN (IPS_UVAS) Page 6  Pharmaceutical Biochemistry II (Theory) Enantiomers Enantiomers are the compounds that are the mirror images of each other with reference to asymmetric carbon atoms in their molecules are called enantiomers. Both can rotate the plane polarized light and the degree of optical rotation in each compound is exactly the same but opposite in directions e.g. L- glucose and D- glucose are the enantiomers of each other. Every sugar exists in L and D form is mirror image of each other except dihydroxyacetone. H C O H C O 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 The name D and L depends upon the position of the –OH group on the last asymmetric carbon atom of the monosaccharides. The enantiomers possess similar physicochemical Dr. KASHIF KHAN (IPS_UVAS) Page 7  Pharmaceutical Biochemistry II (Theory) properties. It is even difficult to separate them. If they need to separate out they should convert to the diastereomers. Diastereoisomers Diastereoisomers (that have one or more chiral centers) are the compounds that are not mirror images of each other and different only with respect to configuration around the asymmetric carbon atoms and rotate the plane-polarized lights in same direction but with different speed are called diastereoisomers. The phenomenon is called diastereoisomerism. e.g. α-D-glucose and β-D-glucose are the diastereoisomers. Anomers are diastereomers. H O H C OH C HO C H H C OH H C OH H C OH O O HO C H HO C H HO C H H C OH H C OH H C OH H C H C OH H C CH2OH CH2OH CH2OH Alpha-D-Glucose Open chain Beta-D-Glucose (+) 112 D-Glucose (+) 19 Optical activity of carbohydrates Carbohydrates solutions have the property to rotate the plane-polarized light to the right or left. This property is called optical activity of the carbohydrates. This property is due to the presence of the asymmetric carbon atoms in their structures. The sugars rotating the plane- polarized light to left are termed as levorotatory while those which rotate the plane-polarized light to right are termed as dextrorotatory. The levorotation is represented by l or (–) sign while the dextrorotation is represented by d or (+) sign. There is no relation of “D and L” and “(–) and (+)” signs. A sugar may be a D sugar and levorotatory e.g. D-fructose. In the solution, glucose is dextrorotatory and sometimes glucose is called dextrose. Trend of use of “l” and “d” has become deleted. Now a days (–) and (+) signs are used for optical activity. Dr. KASHIF KHAN (IPS_UVAS) Page 8  Pharmaceutical Biochemistry II (Theory) There are some conditions in which the plane-polarized light will neither be rotated to right nor to left. Those are 1. If the compound does not possess an asymmetric carbon atom in its structure. 2. If equal quantities of the dextrorotatory and levorotatory isomers are present. Such mixtures are termed as racemic mixtures. 3. If a compound is a meso compound. Such compounds contain asymmetric carbon atoms but do not rotate the light. This is due to the fact that such compounds have two halves, one rotating the light to the right and the other to the left. This phenomenon is called as internal compensation e.g. meso tartaric acid. Meso tartaric acid Asymmetric Centers and D- and L-Monosaccharides All the monosaccharides except dihydroxyacetone contain one or more asymmetric (chiral) carbon atoms. That is why they are optically active. The simplest aldose, glyceraldehyde, contains one chiral center (the middle carbon atom) and therefore has two different optical isomers, or enantiomers. One of these two forms is designated the D isomer and other is L isomer depending on the sides on which H and OH are attached. Dr. KASHIF KHAN (IPS_UVAS) Page 9  Pharmaceutical Biochemistry II (Theory) Structural representation of sugars A: Fisher projection: straight chain representation B: Haworth projection: simple ring representation C: Conformational representation: chair and boat configurations A: Fischer Projection Formulas In case of Fischer projection formula of glucose, the carbon chain is written vertically with carbon No. 1 at the top and the –H and –OH are written to the left or right. Carbon No.2 in both the cases is an asymmetric carbon atom (the carbon atom to which four different atoms or groups is attached). All carbohydrates having more than 3 carbon atoms have two or more asymmetric carbon atoms. In such compounds, the most distant asymmetric carbon atoms from the carbonyl group having the same configuration as that of the asymmetric carbon atom of the D-glyceraldehyde are called D sugars. On the other hand, all sugars whose farthest asymmetric carbon atoms from the carbonyl group having the same configuration as that of the asymmetric carbon atom of the L-glyceraldehyde are called L sugars. The D and L forms of a sugar are stereoisomers and mirror images of each other and are termed as enantiomers. All sugars are compared with D- and L-glyceraldehydes and thus glyceraldehyde is called the reference sugar. D sugars are most abundantly available in nature than the L sugars. L isomer of monosaccharide are also found in human body e.g. L-xylulose. Open chained form of D-glucose (Fischer projection) Dr. KASHIF KHAN (IPS_UVAS) Page 10  Pharmaceutical Biochemistry II (Theory) B: Haworth Projection Formulas Monosaccharides normally adopt a ring configuration. When a D-glucose adopts a six membered ring structure, a hemiacetal bond is formed between the aldehydic carbonyl group of carbon No 1 and hydroxyl group on carbon No 5 (aldehydes react readily with Alcohols to form hemiacetal). Cyclization of glucose thus result in the formation of ring structure, which is analogous to the structure of pyran, six membered ring containing five carbon and one oxygen atom. Sugars with a six membered pyran ring are designated as pyranose. Cyclization of D-glucose thus yields a cyclic hemiacetal, i.e. glucopyranose. Fructose, on the other hand, forms a five membered furan ring with four carbon and one oxygen atom. The linear form of D-fructose thus cyclize between carbonyl carbon of second carbon (C2) and alcoholic group of the fifth carbon (C5), and yield the hehiketal, i.e. fructofuranose (ketones can react with alcohols to form hemiketals). The smallest monosaccharide having the fructofuranose structure is ribose. The ring structure of sugar was proposed by Haworth and is also called Haworth structures. D-glucose is an aldohexose. The open chain structure of glucose was first suggested by Fischer (Fischer’s projection formula) in 1891. Dr. KASHIF KHAN (IPS_UVAS) Page 11  Pharmaceutical Biochemistry II (Theory) Dr. KASHIF KHAN (IPS_UVAS) Page 12  Pharmaceutical Biochemistry II (Theory) C: Conformational representation (Chair and boat forms D-glucose): Although, Haworth projections are convenient for display of monosaccharide structures. Sometimes glucose can also be representing in the form of chair and boot. Chair form of glucose is more stable. β-D-Glucose (Chair form) β-D-Glucose (boat form) Dr. KASHIF KHAN (IPS_UVAS) Page 13  Pharmaceutical Biochemistry II (Theory) Vant Hoff’s law All aldohexose have 4 asymmetric carbon atoms and according to Vant Hoff’s law (the number of possible optical isomers of a substance are equal to 2 n where n is the number of asymmetric carbon atoms) they are expected to have 2 4 = 16 possible isomers (allose, altrose, glucose, mannose, gulose, idose, galactose, talose in D and L forms). However, in aqueous solutions many monosaccharides including glucose display the property of mutarotation. Due to this property these sugars behave as if they have an extra asymmetric carbon atom. The carbonyl carbon is responsible for this phenomenon. Due to this property, the number of possible isomers for aldohexose become 25 = 32 (16 isomers occurring in α and β forms). α and β forms usually occur in ring form and do not show aldehyde group. Isomerism in carbohydrates Stereoisomerism The word isomer is derived from the Greek words “isos” meaning "equal" and “meros” meaning "part". Isomers are compounds with the same molecular formula but different structural formula e.g. glucose, fructose, mannose and galactose has same molecular formulas i.e. C6H12O6 but different structural formulas. The isomerism which based on the difference in the arrangement of the atoms in the space is called stereoisomerism. Dr. KASHIF KHAN (IPS_UVAS) Page 14  Pharmaceutical Biochemistry II (Theory) H C O CH2OH H C O H C O H C OH C O H C OH H C OH HO C H HO C H HO C H HO C H H C OH H C OH HO C H H C OH H C OH H C OH H C OH H C OH CH2OH CH2OH CH2OH CH2OH Glucose Fructose Galactose Glucose Epimers The stereoisomers that differ in configuration around one specific carbon atom (optically active carbon atom) other than carbonyl carbon are called epimers e.g. glucose and galactose differ from each other only in the position of –OH at Carbon No. 4. Similarly, glucose and mannose are different from each other only in the position of –OH at Carbon No 2. So, both are epimers of each other. Anomers The stereoisomers that differ from each other in configuration around carbonyl carbon only are called anomers. When a monosaccharides cyclizes, its anomeric carbon also becomes asymmetric with two possible forms of their configurations i.e. α and β forms. Such stereoisomers that differ in configuration at the anomeric carbon atom i.e. carbon no 1 in aldoses (e.g. glucopyranose) or carbon no 2 in ketoses (e.g. fructofuranose) are called anomers. e.g. α-D-glucopyranose and β-D-Glucopyranose. Both anomers have different Dr. KASHIF KHAN (IPS_UVAS) Page 15  Pharmaceutical Biochemistry II (Theory) physical and chemical properties. Both α and β anomers are interconvertable in aqueous solution. The process of inter-conversion of as α and β anomers is called mutarotation. Phenomenon of mutarotation is increase with increase in number of OH groups. Other example is α-D-fructofuranose and β-D-fructofuranose. Enantiomers Enantiomers are the compounds that are the mirror images of each other with reference to asymmetric carbon atoms in their molecules are called enantiomers. Both can rotate the plane polarized light and the degree of optical rotation in each compound is exactly the same but opposite in directions e.g. L- glucose and D- glucose are the enantiomers of each other. Every sugar exists in L and D form is mirror image of each other except dihydroxyacetone. Dr. KASHIF KHAN (IPS_UVAS) Page 16  Pharmaceutical Biochemistry II (Theory) H C O H C O 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 The name D and L depends upon the position of the –OH group on the last asymmetric carbon atom of the monosaccharides. The enantiomers possess similar physicochemical properties. It is even difficult to separate them. If they need to separate out they should convert to the diastereomers. Diastereoisomers Diastereoisomers (that have one or more chiral centers) are the compounds that are not mirror images of each other and different only with respect to configuration around the asymmetric carbon atoms and rotate the plane-polarized lights in same direction but with different speed are called diastereoisomers. The phenomenon is called diastereoisomerism. e.g. α-D-glucose and β-D-glucose are the diastereoisomers. Anomers are diastereomers. H O H C OH C HO C H H C OH H C OH H C OH O O HO C H HO C H HO C H H C OH H C OH H C OH H C H C OH H C CH2OH CH2OH CH2OH Alpha-D-Glucose Open chain Beta-D-Glucose (+) 112 D-Glucose (+) 19 Optical activity of carbohydrates Carbohydrates solutions have the property to rotate the plane-polarized light to the right or left. This property is called optical activity of the carbohydrates. This property is due to the Dr. KASHIF KHAN (IPS_UVAS) Page 17  Pharmaceutical Biochemistry II (Theory) presence of the asymmetric carbon atoms in their structures. The sugars rotating the plane- polarized light to left are termed as levorotatory while those which rotate the plane-polarized light to right are termed as dextrorotatory. The levorotation is represented by l or (–) sign while the dextrorotation is represented by d or (+) sign. There is no relation of “D and L” and “(–) and (+)” signs. A sugar may be a D sugar and levorotatory e.g. D-fructose. In the solution, glucose is dextrorotatory and sometimes glucose is called dextrose. Trend of use of “l” and “d” has become deleted. Now a days (–) and (+) signs are used for optical activity. There are some conditions in which the plane-polarized light will neither be rotated to right nor to left. Those are 4. If the compound does not possess an asymmetric carbon atom in its structure. 5. If equal quantities of the dextrorotatory and levorotatory isomers are present. Such mixtures are termed as racemic mixtures. 6. If a compound is a meso compound. Such compounds contain asymmetric carbon atoms but do not rotate the light. This is due to the fact that such compounds have two halves, one rotating the light to the right and the other to the left. This phenomenon is called as internal compensation e.g. meso tartaric acid. Meso tartaric acid Asymmetric Centers and D- and L-Monosaccharides All the monosaccharides except dihydroxyacetone contain one or more asymmetric (chiral) carbon atoms. That is why they are optically active. The simplest aldose, glyceraldehyde, Dr. KASHIF KHAN (IPS_UVAS) Page 18  Pharmaceutical Biochemistry II (Theory) contains one chiral center (the middle carbon atom) and therefore has two different optical isomers, or enantiomers. One of these two forms is designated the D isomer and other is L isomer depending on the sides on which H and OH are attached. Structural representation of sugars A: Fisher projection: straight chain representation B: Haworth projection: simple ring representation C: Conformational representation: chair and boat configurations A: Fischer Projection Formulas In case of Fischer projection formula of glucose, the carbon chain is written vertically with carbon No. 1 at the top and the –H and –OH are written to the left or right. Carbon No.2 in both the cases is an asymmetric carbon atom (the carbon atom to which four different atoms or groups is attached). All carbohydrates having more than 3 carbon atoms have two or more asymmetric carbon atoms. In such compounds, the most distant asymmetric carbon atoms from the carbonyl group having the same configuration as that of the asymmetric carbon atom of the D-glyceraldehyde are called D sugars. On the other hand, all sugars whose farthest asymmetric carbon atoms from the carbonyl group having the same configuration as that of the asymmetric carbon atom of the L-glyceraldehyde are called L sugars. The D and L forms of a sugar are stereoisomers and mirror images of each other and are termed as enantiomers. All sugars are compared with D- and L-glyceraldehydes and thus glyceraldehyde is called the reference sugar. D sugars are most abundantly available in nature than the L sugars. L isomer of monosaccharide are also found in human body e.g. L-xylulose. Dr. KASHIF KHAN (IPS_UVAS) Page 19  Pharmaceutical Biochemistry II (Theory) Open chained form of D-glucose (Fischer projection) B: Haworth Projection Formulas Monosaccharides normally adopt a ring configuration. When a D-glucose adopts a six membered ring structure, a hemiacetal bond is formed between the aldehydic carbonyl group of carbon No 1 and hydroxyl group on carbon No 5 (aldehydes react readily with Alcohols to form hemiacetal). Cyclization of glucose thus result in the formation of ring structure, which is analogous to the structure of pyran, six membered ring containing five carbon and one oxygen atom. Sugars with a six membered pyran ring are designated as pyranose. Cyclization of D-glucose thus yields a cyclic hemiacetal, i.e. glucopyranose. Fructose, on the other hand, forms a five membered furan ring with four carbon and one oxygen atom. The linear form of D-fructose thus cyclize between carbonyl carbon of second carbon (C2) and alcoholic group of the fifth carbon (C5), and yield the hehiketal, i.e. fructofuranose (ketones can react with alcohols to form hemiketals). The smallest monosaccharide having the fructofuranose structure is ribose. The ring structure of sugar was proposed by Haworth and is also called Haworth structures. D-glucose is an aldohexose. The open chain structure of glucose was first suggested by Fischer (Fischer’s projection formula) in 1891. Dr. KASHIF KHAN (IPS_UVAS) Page 20  Pharmaceutical Biochemistry II (Theory) Dr. KASHIF KHAN (IPS_UVAS) Page 21  Pharmaceutical Biochemistry II (Theory) C: Conformational representation (Chair and boat forms D-glucose): Although, Haworth projections are convenient for display of monosaccharide structures. Sometimes glucose can also be representing in the form of chair and boot. Chair form of glucose is more stable. β-D-Glucose (Chair form) β-D-Glucose (boat form) Dr. KASHIF KHAN (IPS_UVAS) Page 22  Pharmaceutical Biochemistry II (Theory) Vant Hoff’s law All aldohexose have 4 asymmetric carbon atoms and according to Vant Hoff’s law (the number of possible optical isomers of a substance are equal to 2n where n is the number of asymmetric carbon atoms) they are expected to have 2 4 = 16 possible isomers (allose, altrose, glucose, mannose, gulose, idose, galactose, talose in D and L forms). However, in aqueous solutions many monosaccharides including glucose display the property of mutarotation. Due to this property these sugars behave as if they have an extra asymmetric carbon atom. The carbonyl carbon is responsible for this phenomenon. Due to this property, the number of possible isomers for aldohexose become 25 = 32 (16 isomers occurring in α and β forms). α and β forms usually occur in ring form and do not show aldehyde group. Dr. KASHIF KHAN (IPS_UVAS) Page 23  Pharmaceutical Biochemistry II (Theory) Chemical Properties of Carbohydrates with special reference to Glucose 1. Formation of Glycosides What are glycosides? Glycosides are molecules in which a sugar (carbohydrate) is bound to a non-sugar moiety (non-carbohydrate). In glycoside molecule, the sugar part is known as glycone and the non-sugar part is known as aglycone par. In the formation of glycosides, hydroxyl group (OH) of anomeric carbon of sugar part reacts with hydroxyl group of non sugars part through glycosidic linkage e.g. Amygdalin. This linkage is formed at anomeric carbon that can be of α or β configuration so the glycosides may α or β glycosides. The aglycone may be attached through –OH or –NH2 group forming O– or N– glycosides respectively. O-glycosides are more common in nature. Oligosaccharides and polysaccharides contain O-glycosidic bonds. N-glycosidic bonds occur in nucleotides and in glycoproteins. Dr. KASHIF KHAN (IPS_UVAS) Page 24  Pharmaceutical Biochemistry II (Theory) 2. Formation of Osazone What is Osazone? Osazone is yellowish, crystalline compound, produced as a result of heating sugars solutions with phenylhydrazine. Osazones are formed by those sugars which contain a free aldehyde or ketone group. For example one molecule of glucose reacts with three molecules of phenyl hydrazine to form glucosazone. On the other hand sucrose doesn’t possess free aldehyde or ketone group and thus cannot form Osazone until it is first hydrolyzed to monosaccharides. Dr. KASHIF KHAN (IPS_UVAS) Page 25  Pharmaceutical Biochemistry II (Theory) Glucosazone (x 250) Maltosazone (x 250) Galactosazone (x 160) Lactosazone (x 250) Figure showing different types of Osazone crystals 3. Formation of sugar alcohols The aldehyde or ketone group of both aldoses and ketoses can be reduced to form the corresponding polyhydroxy alcohols. Glucose reduces to form sorbitol and fructose reduces to form sorbitol and mannitol. Dr. KASHIF KHAN (IPS_UVAS) Page 26  Pharmaceutical Biochemistry II (Theory) Monosaccharides Corresponding Alcohol Glucose Sorbitol Mannose Mannitol Galactose Dulcitol Fructose Sorbitol & Mannitol Ribose Ribitol Glyceraldehyde Glycerol Dihydroxyacetone Glycerol Mannitol is frequently use in the patients of cerebral edema because it act as osmotic diuretic and decrease the water content of the body and thus decrease the brain swelling. Sorbitol is getting deposited in the lens of the eye especially in the patients of diabetes mellitus and contributes to the early cataract formation. Dr. KASHIF KHAN (IPS_UVAS) Page 27  Pharmaceutical Biochemistry II (Theory) 4. Formation of sugar acid Carbohydrates form the sugar acid on their oxidation. When glucose (aldoses) is oxidized under proper conditions, then it yields three types of sugar acids; namely gluconic acid, glucuronic acid, and glucaric acid. i. Gluconic acid is formed under mild conditions and due to oxidation at C-1. Gluconic acid is used in the formation of salts of different drugs e.g. antimalarial drugs. Glucuronic acid is formed by oxidation at C-6. Glucuronic acid is formed in the body. It is of great physiological importance because it is use in the body as detoxifying agent and inactivates the many substances like camphor, benzoic acid, steroid hormones and bilirubin etc. iii. Glucaric acid is formed via oxidation of glucose at C-1 & C-6. Dr. KASHIF KHAN (IPS_UVAS) Page 28  Pharmaceutical Biochemistry II (Theory) 5. Reducing Properties of sugar in alkaline solutions. Almost, all carbohydrates contain a free aldehyde or ketone group except sucrose. That is oxidized in alkaline pH. So, they are good reducing agents in an alkaline medium. They readily reduce oxidizing ions such as Ag+, Hg2+, Bi3+, Cu2+, and ferricyanide3+. \ This reaction is the basis for the Benedict’s test and Fehling’s test. 6. Action of acids on carbohydrates Monosaccharides are resistant to the action of hot diluted acids. Strong acids dehydrate all carbohydrates leading to the formation of furfural ring. These products condense with phenols to form characteristic colored products. Dr. KASHIF KHAN (IPS_UVAS) Page 29  Pharmaceutical Biochemistry II (Theory) This reaction is the basis of the color test, known as Molisch’s test for sugars. 7. Action of bases on carbohydrates Dilute basic solutions at low temperature can bring about re-arrangement of groups at the anomeric carbon atoms and its adjacent carbon atom. For example glucose can be changed to fructose and mannose. Higher concentration of bases can cause the further changes i.e. more carbon atoms show the rearrangement of the groups and even fragmentation and polymerization occur. 8. Esters formation Hydroxyl group of sugar can be esterifies with phosphates, acetates, propionates and stearates etc. Sugar phosphates are of great biological significance. Nucleoproteins of cells contain sugar phosphate in combination with various nitrogen bases. Dr. KASHIF KHAN (IPS_UVAS) Page 30  Pharmaceutical Biochemistry II (Theory) 9. Amino sugars formation A hydroxyl group of the monosaccharides can be replaced by an amino group (–NH2) forming an amino sugar e.g. example D-glucosamine, D-galactosamine, D-fructosamine. In all these –NH2 group is attached at C-2. These are present in nature. As they are derived by hexoses so they are also called hexosamine. Glucosamine is constituent of hyaluronic acid. Galactosamine is present in chondroitin. Mannosamine is an important constituent of mucoproteins. Aminosugars also occur in many antibiotics e.g. erythromycin. In most cases amino sugar is N-acetylated. 10. Fermentation Fermentation is the process of converting a larger complex molecule into simple molecules by means of enzymes. Some of the hexoses sugars are converted to ethanol and CO 2 by a group of enzymes called as zymases. Dr. KASHIF KHAN (IPS_UVAS) Page 31  Pharmaceutical Biochemistry II (Theory) C6H12O6 → 2(C2H5OH) + 2CO2 Glucose Ethanol Carbondioxide Glucose, fructose and mannose can be readily fermented by common baker yeast. Galactose is fermented to negligible amount. Importance of Carbohydrates 1. Carbohydrates are widely distributed in plants and animals and have important structural and metabolic roles. 2. In plants, carbohydrates are synthesized from carbon dioxide and water by photosynthesis and stored as starch or used to synthesize cellulose. 3. Animals can synthesize carbohydrate from lipid, glycerol and amino acids, but in most animal carbohydrate is derived from plants sources. 4. Most dietary carbohydrate is absorbed into the bloodstream as glucose, and other sugars are converted into glucose in the liver. Glucose is the major metabolic fuel of mammals and universal fuel of the fetus. 5. It is the precursor for synthesis of all the other carbohydrates in the body, including glycogen for storage; ribose and deoxyribose in nucleic acids; and galactose in lactose of milk. Glucose is also present in glycolipids and in glycoproteins. 6. Various diseases associated with carbohydrate metabolism include diabetes mellitus, galactosemia, glycogen storage diseases, and lactose intolerance. 7. Oligosaccharides are present in combination with proteins at all cell membranes. 8. These are also present in secreted proteins such as antibodies and blood clotting factors. 9. Complexes of carbohydrates with proteins act as receptors on cell membranes which are thus involved in molecular recognition. 10. Carbohydrate derivatives such as heparin are used in the development of nervous system. Dr. KASHIF KHAN (IPS_UVAS) Page 32  Pharmaceutical Biochemistry II (Theory) 11. Ribose is an integral part of high energy phosphate compounds i.e., ATP, GTP (guanosine triphosphate), UTP (uridine triphosphate) and CTP (cytidine triphosphate) and secondary messengers such as cAMP (cyclic adenosine monophosphate) and cGMP ((cyclic guanosine monophosphate). http://images.google.com.pk/imgres?imgurl=http://web.virginia.edu/Heidi/chapter7/Ima ges/8883n07_10.jpg&imgrefurl=http://web.virginia.edu/Heidi/chapter7/chp7.htm&usg= __0lZzP7dbaVYwo9wznnCVcE6W- PA=&h=419&w=516&sz=26&hl=en&start=4&tbnid=IVG2x07Ea-- zvM:&tbnh=106&tbnw=131&prev=/images%3Fq%3Dformation%2Bof%2Bglucaric% 2Bacid%26gbv%3D2%26hl%3Den%26safe%3Dactive Dr. KASHIF KHAN (IPS_UVAS) Page 33