Carbohydrate Chemistry PDF

# Carbohydrate Chemistry ## Derivatives of Monosaccharide - The 5 major groups of monosaccharide derivatives: 1. **Sugar Phosphates** - **Glucose-6-Phosphate**: Phosphate attached to the 6th carbon of glucose. 2. **Sugar alcohols** - **Sorbitol**: Reduced form of glucose....

# Carbohydrate Chemistry ## Derivatives of Monosaccharide - The 5 major groups of monosaccharide derivatives: 1. **Sugar Phosphates** - **Glucose-6-Phosphate**: Phosphate attached to the 6th carbon of glucose. 2. **Sugar alcohols** - **Sorbitol**: Reduced form of glucose. 3. **Sugar acids** - **B-D-2-deoxyglucose**: Glucose missing the hydroxyl group at the 2nd carbon. 4. **Deoxy Sugars** - **B-D-2-glucosamine**: Amino group replaces the hydroxyl group at the 2nd carbon. 5. **Amino Sugars** - **B-D-glucuronic acid**: Glucose with a carboxylic acid group instead of the hydroxyl group at the 6th carbon. ## Sugar Phosphate 'ester bond' - Phosphorylation reactions are catalyzed by a family of enzymes called protein kinases that use adenosine triphosphate (ATP) as a phosphate donor. - 'Phosphate or Pi' ## Sugar acids - are produced by oxidation of carbonyl carbon, last hydroxyl carbon or both. 1. **Aldonic acids (C1):** oxidation of carbonyl carbon to carboxylic group gives aldonic acid. - e.g. glucose is oxidized to gluconic acid. 2. **Uronic acids (C6):** oxidation of last hydroxyl carbon gives uronic acid e.g. glucose is oxidized to glucuronic acid. 3. **Aldaric acids (C1 & C6):** These are dicarboxylic acids produced by oxidation of both carbonyl carbon and last hydroxyl carbon e.g. glucose is oxidized to glucaric acid. ## Sugar alcohols - Monosaccharides, both aldoses and ketoses may be reduced at carbonyl carbon, to the corresponding alcohol. 1. Glucose is reduced to glucitol (sorbitol). 2. Galactose is reduced to galactitol (dulcitol). 3. Mannose is reduced to mannitol. 4. Fructose is reduced to mannitol and sorbitol. ## Deoxy-sugars - Are sugars in which one of the hydroxyl groups has been replaced by a hydrogen atom i.e. one oxygen is missed. - Deoxyribose found in ATP & nucleic acid 'DNA'. - **L-Fucose (Fuc):** 6-Deoxygalactose or methyl pentose: occurring in glycoproteins. ## Amino sugars - In these sugars, the hydroxyl group attached to carbon number 2 is replaced by an amino or an acetyl-amino group. 'CH_3CO-NH-sugar' - Amino sugars are important components of glycoproteins, of certain glycol-sphingo-lipids, and of glycosaminoglycans (GAGs), and are also found in some antibiotics. The synthetic pathway of amino sugars is very active in connective tissues, where as much as 20% of glucose flows through this pathway. - The major amino sugars are the hexosamines glucosamine, galactosamine, and mannosamine, and the compound sialic acid (nine-carbon; 3C+6C). - **2-amino-glucose or glucosamine** - **N-acetyl-glucosamine or GluNac** - **Glucosamine** ## Amino Sugar acids - Are a condensation of amino sugars and some acids. They are occurring in glycoproteins. - **For Example: Sialic acid or N-Acetyl Neuraminic Acid** - **Neuraminic acid (NANA)/Sialic acid** ## Glycosidic Bonds - **Naming glycosidic bonds:** named according to the numbers of the connected C, and with regard to the position of the anomeric -OH group of the sugar involved in the bond. If this anomeric hydroxyl is in the a configuration, the linkage is an a-bond. If it is in the ß configuration, the linkage is a ß-bond. - **Maltose, for example, is synthesized by forming a glycosidic bond between C1 of A-glucose and C4 of glucose. The linkage is, therefore, an a(1→4) glycosidic bond.** ## N- and O-glycosides - **Naming glycosidic bonds 'N- and O-glycosides':** These carbohydrates are attached to either the side-chain Oxygen (group is an -OH) of serine or threonine residues by **O-glycosidic** linkages or to the side chain nitrogen (an -NH_2 group) of Asparagine residues by **N-glycosidic** linkages. ## Disaccharide - The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond. - They subdivide based on presence or absence of free reducing group into: - **Reducing disaccharides** with free aldehyde or keto group - **Example:- Maltose and Lactose** - **Non reducing disaccharide** without free aldehyde or keto group - **Example:- Sucrose** - Hydrolysis of sucrose yields a mixture of glucose and fructose called "invert sugar" because fructose is strongly levorotatory and changes (inverts) the weaker dextrorotatory action of sucrose. ## Sucrose - It is commonly used table sugar and contributes some calories in the diet. - It contains one mole of glucose and one mole of fructose that are linked by a-(1-2) glycosidic linkage. It hydrolyzed into glucose and fructose by the enzyme Sucrase is also called as Invertase. It is a non reducing disaccharide. ## Maltose - It contains two moles of glucose units. - They linked by a-(1-4) glycosidic linkage. - It is a one of the reducing disaccharide, which has free functional group. - It hydrolyzed to two glucose by an enzyme called maltase. ## Isomaltose - It is also contains two moles of glucose. - They linked by a-(1-6) glycosidic linkage. - It is derived from the digestion of starch & glycogen. - It hydrolyzed to glucose in the intestinal tract by an enzyme called isomaltase. ## Lactose - It is present in the milk sugar. It is the source of carbohydrates in breast fed infants. - Its contains one mole of galactose and one mole of glucose that are linked by B-(1-4) glycosidic linkage. It is also a reducing disaccharide. - It hydrolyzed into galactose and glucose by the enzyme lactase in human and by B-D-galactosidase in bacteria. ## Polysaccharides - Polysaccharides are long chains of monosaccharides joined together by glycosidic bonds (linkages). Polysaccharides have been classified into two groups : - **(i) homopolysaccharides (also called homoglycans)** containing only one type of monosaccharide glycose units, and - **(ii) heteropolysaccharides (also called heteroglycans)** containing atheist two different monosaccharides (or glycose) units. Most heteropoly- saccharides do not contain more than two types of glycose units. These polysaccharides are formed due to condensation of many molecules of monosaccharides With simultaneous release of water molecules. Because each monosaccharide has several free hydroxyl groups that can be used for condensation with another monosaccharide: the number of possible structures of a polysaccharide involving the same monosaccharide units. can large. ## Homopolysaccharides - **Homopolysaccharides (homoglycans)** consist of same monosaccharide units (e.g. glucose, fructose, galactose, mannose. xylose, etc.). - Cellulose, glycogen, and starch are the best-known examples. However, they have very different properties. - **Glycogen** is found in animals While, **starch and cellulose** are in plants. - All of them are composed of only glucose residues. - While glycogen and starch are used for storing energy, **cellulose** makes the extracellular matrix (ECM) or cell wall in plants. - Different homopolysaccharides, their repeat units and the linkage type in each case. ## Homopolysaccharides: 1. Starch - **Starch:** a homopolymer composed of D-glucose units or (D-glucopyranose units) held by A- glycosidic bonds, and occurs in many plants. - **Composition of starch granule:** It consists of two polymeric (1) water soluble **amylose** (15 -20%) and (ii) water insoluble **amylopectin** (80-85%). - Starch consists of amylose and amylopectin in the ratio of 1: 4. - **Chemically, Amylose** is a linear polysaccharide linked by a(1-4) linkages while **amylopectin** is a branched polysaccharide [The linear linkage is a(1-4) while the branched linkage is a(1-6)]. - **Amylopectin:** Approx. 80 branches, One branch after every 24 to 30 D-Glucose units. ## Starch Hydrolysis - **Types of amylases:** 1. **a-amylase** an endoenzyme: is present in saliva and pancreatic secretion. 2. **ß-amylase** an exoenzyme is present in sprouted grains and malts. - Both of them hydrolyze only a-glycosidic linkage. - **Endoenzyme:** - **Alpha-Amylase** an endoenzyme, which hydrolyze interior A-(1→4) glucosidic linkages in amylose and amylopectin, and has very low activity against the bonds of terminal glucose units. Additionally, it cannot hydrolyze the Q-1,6 linkages in amylopectin. These linkages a -(1→6) can be hydrolyzed by isoamylases and pullulanases. - The resulting products of amylase acting on starch, referred to as dextrins, are Q-1,4-linked glucose dimers (maltose), Q-1,4-linked glucose trimers (maltotriose), and branched oligosaccharides of 6 to 8 glucose units that contain both A-1,6 and A-1,4 linkages (limit dextrins). - **Exo-enzymes:** - **Beta-amylases** are exo-enzymes that attack the substrate from the nonreducing end and hydrolyze A-(1→4) glucosidic linkages. - **Maltose** (disaccharide) molecules are detached from the non-reducing end during hydrolysis by beta-amylase. - In addition, glucan (14)-a-glucosidases hydrolyze A-(1→4)- and A-(1→6) glucosidic linkages from the nonreducing end, yielding d-glucose. - Whereas beta amylases have higher activity on poly-saccharides as compared to oligosaccharides, the reverse is the case for A-glucosidases. These exo-enzymes A-(1→4)-linked [and in some cases A-(1→6)-linked] oligosaccharides to glucose. - Note: Glucans are consist of oligosaccharides and polysaccharides. ## 2. Glycogen - Glycogen is the main storage polysaccharide occurring in animal cells, so it referred as animal starch. It is present in high concentration in liver, followed by muscle, brain etc. - Liver glycogen response to blood glucose (BG) levels: - BG - glycogen breakdown - BG - Muscle glycogen can be broken down for energy for the muscle. - Its structure is very similar to amylopectin, in that main chain linkages between D-glucose units are (14) and the linkages at branch points are (16). - Branch points occur more frequently in glycogen (about every 8 to 12 residues) than in amylopectin. ## 3. Cellulose - The main component of plant cell wall. - An unbranched polymer (a linear homopolysaccharide ) of glucose linked by B-(1-4) glycosidic linkages. 'Due to the presence of B linkages, cellulose chains fold quite differently than chains of D- glucose in the starches and glycogen' - Since humans lack an enzyme cellulase that can hydrolyse B-(1-4) glycosidic linkages, cellulose cannot be digested and absorbed. 'This enzyme are produced by many cellulolytic microorganisms'. - has no food value unlike starch. ## Importance of Cellulose - Cellulose, though not digested/hos great importance in human. - It is a major constituent of fiber, the non-digestible carbohydrate. - The functions of dietary fiber include: - decreasing the absorption of glucose and cholesterol from the intestine, - Aids intestinal mobility and prevent constipation. ## 4. Chitin - A linear homopolysaccharide, It is a polymer of units of N-acetyl glucosamine which is linked by ẞ(1-4) glycosidic bond. - It is similar to cellulose in both structure and function. - The only chemical difference from cellulose is the replacement of the hydroxyl group at C-2 with an acetylated amino group. - Chitin is the principal component of the hard exoskeletons of nearly a million species of Arthropods (insects and crabs). ## 5. Dextrans and Dextrins - Dextrans are bacterial and yeast polysaccharides made up of (16) -linked poly-D-glucose; all have (13) branches, and some also have (12) or (14) branches. - Dental plaque, formed by bacteria growing on the surface of teeth, is rich in dextrans. - Dextrins, When starch is partially hydrolysed by the action of acids or enzymes, it is broken down into a number of products of lower molecular weight known as dextrins. ## 6. Inulin - Inulin composed of 2 - 60 fructose molecules connected by ẞ-(2→1) glycoside bonds. - Inulin structure and functions Inulin as a reserve carbohydrate in many plants (in the in the roots of the artichoke, dandelion and in the bulbs of onion and garlic). - Acids hydrolyze of Inulin given to D-fructose; similarly it is also hydrolysed by the enzyme inulinase, which accompanies it in plants. It has no dietary importance in human beings as inulinase is absent in human. - **Biomedical Importance:** - It is used in physiological investigation for determination of the rate of glomerular filtration rate (GFR). - It has been also used for estimation of body water (ECF) volume. ## Heteropolysaccharides - Heteropolysaccharides (heteroglycans) consist of more than one monosaccharides. Sometimes, the repeating unit is a disaccharide. - **Glycosaminoglycans (GAGs):** - GAGs are linear polymers of repeating disaccharide units [acidic sugar-amino sugar]n - The amino sugar (usually acetylated) is either D-glucosamine or D-galactosamine. The amino sugar may also be sulfated on carbon 4 or 6 or on a nonacetylated nitrogen. - The acidic sugar is either D-glucuronic acid or its C-5 epimer, L-iduronic acid. - GAGS are strongly negatively charged: carboxyl groups of acidic sugars & Sulfate groups. - **The important Glycosaminoglycans are:** - Hyal hyaluronic acid - Chondroitin 4-sulfate - Heparin - Dermatan sulfate and - Keratan sulfate ## Digestion and Absorption of Carbohydrates ### A. Digestion in Mouth - Digestion of carbohydrate starts at the mouth. In mouth, food undergoes mastication. During mastication, food comes in contact with saliva(secreted by salivary gland). Saliva contain salivary amylase (alpha-amylase called ptyalin). - **Action of salivary amylase:** - It requires Cl ion for activation and PH 6.7. - The enzyme hydrolyzes a-(1-4) glycosidic bonds at random deep inside polysaccharide (starch, glycogen). - Producing dextrins, maltotriose, maltose, and Isomaltose. ### B. Digestion in Stomach - Carbohydrate digestion halts temporarily in the stomach, because the high acidity (pH 1.2 to 3) inactivates salivary Q-amylase. - No enzymes are available in gastric juice of carbohydrate digestion. ### C. Further digestion of carbohydrates by pancreatic enzymes - occurs in the small intestine. When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic Q-amylase continues the process of starch digestion. - **pancreatic amylase.** It hydrolyzes the dextrin to mixture of maltose, isomaltose, limit dextrin. ### D. Final carbohydrate digestion by enzymes synthesized by the intestinal mucosal cells (a-glucosidases) - Final hydrolysis of di- and oligo-saccharides to monosaccharides is carried out by a-glucosidases on the surface of the small intestine (intestinal brush border enzyme). - **isomaltase** cleaves the a(1→6) bond in isomaltose and maltase cleaves maltose and maltotriose, each producing glucose, - **sucrase** cleaves sucrose producing glucose and fructose, - **lactase** (β-galactosidase) cleaves lactose producing galactose and glucose. ### E. Absorption of Carbohydrates - Monosaccharides are absorbed by carrier mediated transport. At least two types are known: - 1) sodium dependent glucose transporters (SGLT) 'Na* monosaccharide transporter'. - 2) sodium independent glucose transporters (GLUT) 'diffusion type monosaccharide transport system. - **Glucose transporters:** - Glucose is polar molecule so it can not pass through lipid bilayer there are 2 types of transporters for transport of glucose - 1) sodium dependent glucose transporters (SGLT): - Sodium dependent transporter this is a form of co-transport, because sodium binds first, which causes structural changes in the transporter which allows glucose or galactose) to bind. - Sodium is transported across cell membrane from high to concentration and glucose is transported against concentration into the cell, from here, ATP is used to pump sodium out via the Na+/K+ ATPase pump - 2) sodium independent glucose transporters (GLUT): These transporters are used for facilitated Diffusion GLUT (1-14) are numbered - - **FINAL PRODUCTS OF CARBOHYDRATE DIGESTION** - 80% glucose - 10% fructose - 10% galactose - The final result of the digestion of carbohydrates in the form of glucose is transported into the cell as a source of energy, while fructose and galactose is transported directly into the liver for conversion into glucose. - since only monosaccharides are able to pass through the plasma membrane at the site of absorption. Mouth and esophagus.