Carbohydrates CARBOHYDRATES Monosaccharides Oligosaccharides Polysaccharides Glyconoconjugates ROLE OF

Carbohydrates

CARBOHYDRATES • • Monosaccharides Oligosaccharides Polysaccharides Glyconoconjugates

ROLE OF CARBOHYDRATES • • As a major energy source for living organisms As a means of transporting energy As a precursor for other biomolecules As a structural material

CARBOHYDRATES Carbohydrate compounds contain H, C & O with the composition : (CH 2 O)n (Hydrate of carbon) Carbohydrates : Consist of sugar Sugars : compound that contains alcohol and carbonyl functional group Carbonyl group : >C=o Adehyde aldose Ketone ketose

Classification of CARBOHYDRATES Carbohydrates: n MONOSACHARIDES n OLIGOSACHARIDES n POLYSACHARIDES

MONOSACCHARIDES Simple Carbohydrates

Monosaccharides : aldoses, ketoses Aldotriose Ketotriose Aldotetrose Ketotetrose Aldopentoses Aldohexose Ketopentose Ketohexose

MONOSACCHARIDES STEREOISOMERS n n n ISOMERS- compounds that have the same chemical formula e. g. fructose, glucose, mannose, and galactose are isomers of each other having formula of C 6 H 12 O 6. EPIMERS- refer to sugars whose configuration differ around one specific carbon atom e. g. glucose and galactose are C-4 epimers and glucose and mannose are C-2 epimers. ENANTIOMERS- a special type of isomerism found in pairs of structures that are mirror images of each other. The mirror images are termed as enantiomers and the two members are designated as D - and L- sugar. The vast majority of sugars in humans are D-sugars. CYCLIZATION OF SUGARS- most monosaccharides with 5 or more carbon atoms are predominately found in a ring form, where the aldehyde or ketone group has reacted with an alcoholic group on the same sugar group to form a hemiacetal or hemiketal ring. Pyranose ring: if the ring has 5 carbons and 1 oxygen. Furanose ring: if the ring is 5 -membered (4 carbons and 1 oxygen)

D- and LEnantiomers

FISHER AND HAWORTH FORMS OF SUGAR

REACTIONS IN MONOSACCHARIDES • • • Oxidation Reduction Isomerization Esterification Glycoside formation Mutarotation

REACTIONS IN MONOSACCHARIDES Oxidation and reduction in presence of oxidising agents, metal ions (Cu 2+) and enzymes, monosacchs undergo several oxidation reactions e. g. Oxidation of aldehyde group (R-CHO) yields aldonic acid; of terminal CH 2 OH (alcohol) yields uronic acid; and of both the aldehyde and CH 2 OH gives aldaric acid. The carbonyl groups in both aldonic and uronic can react with an OH group. n Reduction reduction of the aldehyde and ketone groups of monosacchs yield sugar alcohols (alditols) Sugar alcohols e. g. sorbitol, are used commercially in processing foods and pharmaceuticals. e molecule to form a cyclic ester lactone. n Mutarotation alfa and beta forms of sugars are readily interconverted when dissolved in water. n

REACTIONS 4. 5 6. ISOMERIZATION Monosaccharides undergo several types of isomerization e. g. D-glucose in alkaline solution for several hours containn Dmannose and D-fructose. The conversion of glucose to mannose is termed s epimerization. ESTERIFICATION Free OH groups of carbohydrates react with acids to form esters. This reaction an change the physical and chemical propteries of sugar. GLYCOSIDE FORMATIONHemiacetals and hemiketals reaction with alcohols to form the corressponding aceta or ketal (p. 210 of Text). On the contrary when a cyclic hemiacetal or hemiketal form of monosaccharide reacts with alcohol, the new linkage is called glycosidic linkage and the compound glycoside.

REDUCING SUGARS • • • All monosacchs are reducing sugars. They can be oxidised by weak oxidising agent such as Benedict’s reagent Benedict's reagent is a solution of copper sulfate, sodium hydroxide, and tartaric acid.

IMPORTANT MONOSACCHARIDES • • • GLUCOSE FRUCTOSE GALACTOSE • D-Glucose: • D-glucose (dextrose) is the primary fuel in living cells especially in brain cells that have few or no mitochondria. • Cells such as eyeballs have limited oxygen supply and use large amount of glucose to generate energy • Dietary sources include plant starch, and the disaccharides lactose, maltose, and sucrose

Diabetes Mellitus • • • Characterized by high blood glucose levels that splills over into the urine These high glucose levels impairs the insulinstimulated glucose entry into cells and starve the cells of insulin. This leads to ketosis or high levels of ketone bodies (acids) that hinders the buffering capacity of the blood in the kidney, which controls blood p. H (by excreting excess H+ ions into the urine). The H+ excretion is accompanied by the excretion ammonia, sodium, potassium, and phosphate ions causing severe dehydration This leads to excessive thirst symptom of diabetes and life-threatening decrease in blood volume.

Important monosaccharides. Continued • FRUCTOSE u D-fructose (levulose) is often referred as fruit sugar and is found in some vegetables and honey u This molecule is an important member of ketose member of sugars u It is twice as sweet as sucrose (per gram basis) and is used as sweeting agent in processed food products u It is present in large amounts in male reproductive tract and is synthesised in the seminal vesicles.

Important Monosaccharides • GALACTOSE u is necessary to synthesize a variety of biomolecules (lactose-in mammalary glands, glycolipids, certain phospholipids, proteoglycans, and glycoproteins) u Galactose and glucose are epimers at carbon 4 and interconversion is catalysed by enzyme epimerase. u Medical problems – galactosemia (genetic disorder) where enzyme to metabolize galactose is missing; accumulation of galactose in the body can cause liver damage, cataracts, and severe mental retardation

MONOSACCHARIDE DERIVATIVES • URONIC ACIDS – formed when terminal CH 2 OH group of a mono sugar is oxidised u Important acids in animals – D-glucuronic acid and its epimer L-iduronic acid u In liver cells glucuronic acid combines with steroids, certain drugs, and bilirubin to improve water solubility therby helping the removal of waste products from the body u These acids are abundant in the connective tissue carbohydrate components.

Mono Sugar Derivatives n AMINO SUGARS u Sugars in which a hydroxyl group (common on carbon 2) is replaced by an amino group e. g. D-glucosamine and D-galactosamine u common constituents of complex carbohydrate molecule found attached to cellular proteins and lipids u Amino acids are often acetylated e. g. N-acetyl -glucosamine.

Mono sugar derivatives • DEOXYSUGARS u monosaccharides in which an - H has replaced an – OH group u Important sugars: L-fucose (formed from Dmannose by reduction reactions) and 2 -deoxy-Dribose u L-fucose – found among carbohydrate components of glycoproteins, such as those of the ABO blood group determinates on the surface of red blood cells u 2 -deoxyribose is the pentose sugar component of DNA.

GLYCOSIDES • • Monosaccharides can be linked by glycosidic bonds (joining of 2 hydroxyl groups of sugars by splitting out water molecule) to create larger structures. Disaccharides contain 2 monosaccharides e. g. lactose (galactose+glucose); maltose (glucose+glucose); sucrose (glucose+fructose) Oligosaccharides – 3 to 12 monosaccharides units e. g. glycoproteins Polysaccharides – more than 12 monosaccharides units e. g. glycogen (homopolysaccharide) having hundreds of sugar units; glycosaminoglycans (heteropolysaccharides) containing a number of different monosaccharides species.

DISACCHARIDES AND OLIGOSACCHARIDES

DISACCHARIDES AND OLIGOSACCHARIDES • • • Configurations: alpha or beta ( 1, 4, glycosidic bonds or linkages; other linkages 1, 1; 1, 2; 1, 3; 1, 6) Digestion aided by enzymes. Defficiency of any one enzyme causes unpleasant symptoms (fermentation) in colon produces gas (bloating of cramps). Most common defficiency, an ancestoral disorder, lactose intolerance caused by reduced synthesis of lactase.

Important Sugars of Disaccharides are joined through an “oxygen bridge”. The carbonoxygen bonds are called glycosidic bonds. The most common disaccharides are lactose, sucrose and maltose. • • LACTOSE Disaccharide found in milk; composed of one molecule of galactose and glucose linked through beta(1, 4) glycosidic linkage; because of the hemiacetal group of the glucose component, lactose is a reducing sugar.

• MALTOSE • An intermediate product of starch hydrolysis. It is a disaccharide with an alfa(1, 4) glycosidic linkage between two D-glucose molecules. • SUCROSE • Common table sugar: cane sugar or beet sugar produced in the leaves and stems of plants; it is a disaccharide containing both alfaglucose and beta-fructose residues linked by alfa, beta (1, 2) glycosidic bond. • CELLOBIOSE • Degradation product of cellulose containing two molecules of glucose linked by a beta (1, 4) glycosidic bond; it does not occur freely in nature.

OLIGOSACCHARIDE SUGARS • • • Oligosaccharides are small polymers often found attached to polypeptides in glycoproteins and some glycolipids. They are attached to membrane and secretory proteins found in endoplasmic reticulum and golgi complex of various cells Two classes: N-linked and O-linked.

POLYSACCHARIDES

Polysaccharides • • • Composed of large number of monosaccharide units connected by glycosidic linkages Classified on the basis of their main monosaccharide components and the sequences and linkages between them, as well as the anomeric configuration of linkages, the ring size (furanose or pyranose), the absolute configuration (D- or L-) and any other substituents present. Polysaccharides are more hydrophobic if they have a greater number of internal hydrogen bonds, and as their hydrophobicity increases there is less direct interaction with water

Classification of Polisaccharides n Polisaccharides are divided into homopolysaccharides (e. g. Starch, glycogen, cellulose, and chitin) and heteropolysaccharides (glycoaminoglycans or GAGs).

HOMOSACCHARIDES • • • Found in abundance in nature Important examples: starch, glycogen, cellulose, and chitin Starch, glycogen, and cellulose all yield Dglucose when they are hydrolyzed Cellulose - primary component of plant cells Chitin – principal structural component of exoskeletons of arthropods and cell walls of many fungi; yield glucose derivative Nacetyl glucosamine when it is hydrolyzed.

STARCH • • • A naturally abundant nutrient carbohydrate, (C 6 H 10 O 5)n, found chiefly in the seeds, fruits, tubers, roots, and stem pith of plants, notably in corn, potatoes, wheat, and rice, and varying widely in appearance according to source but commonly prepared as a white amorphous tasteless powder. Any of various substances, such as natural starch, used to stiffen cloth, as in laundering. Two polysaccharides occur together in starch: amylose and amylopectin Amylose – unbranched chains of D-glucose residues linked with alpha(1, 4, )glycosidic bonds Amylopectin – a branched polymer containing both alpha (1, 4, ) and alpha(1, 6) glcosidic linkages; the alpha(1, 6) branch points may occur every 20 -25 glucose residues to prevent helix formation Starch digestion begins in the mouth; alfa-amylase in the saliva initiates hydrolysis of the gycosidic linkages.

GLYCOGEN • • • Glycogen is the storage form of glucose in animals and humans which is analogous to the starch in plants. Glycogen is synthesized and stored mainly in the liver and the muscles. Structurally, glycogen is very similar to amylopectin with alpha acetal linkages, however, it has even more branching and more glucose units are present than in amylopectin. The structure of glycogen consists of long polymer chains of glucose units connected by an alpha acetal linkage. The branches are formed by linking C # 1 to a C # 6 through an acetal linkages. In glycogen, the branches occur at intervals of 8 -10 glucose units, while in amylopectin the branches are separated by 1220 glucose units.

CELLULOSE • • • Cellulose is found in plants as microfibrils (2 -20 nm diameter and 100 - 40 000 nm long). These form the structurally strong framework in the cell walls. Cellulose is mostly prepared from wood pulp Cellulose is a linear polymer of β-(1 4)-D-glucopyranose units in 4 C conformation. The fully equatorial conformation of β-linked 1 glucopyranose residues stabilizes the chair structure, minimizing its flexibility Cellulose has many uses as an anticake agent, emulsifier, stabilizer, dispersing agent, thickener, and gelling agent but these are generally subsidiary to its most important use of holding on to water. Water cannot penetrate crystalline cellulose but dry amorphous cellulose absorbs water becoming soft and flexible. Purified cellulose is used as the base material for a number of water-soluble derivatives e. g. Methyl cellulose, carbomethycellulose

CHITIN • Structure of the chitin molecule, showing two of the N-acetylglucosamine units that repeat to form long chains in beta-1, 4 linkage. • • • Chitin is unusual because it is a "natural polymer, " or a combination of elements that exists naturally on earth. Usually, polymers are man-made. Crabs, beetles, worms and mushrooms contain large amount of chitin. Chitin is a very firm material, and it help protect an insect against harm and pressure

HETEROPOLYSACCHARIDES • • Are high-molecular-weight carbohydrate polymers more than one kind of monosaccharide Important examples include glycosaminoglycans (GAGs) – the principle components of proteoglycans and murein, a major component of bacterial cell walls.

Glycosaminoglycans (GAGs) High-molecular-weight carbohydrate polymers • • Glycosaminoglycans forming the proteoglycans are the most abundant heteropolysaccharides in the body. They are long unbranched molecules containing a repeating disaccharide unit. Usually one sugar is an uronic acid (either D-glucuronic or L-iduronic) and the other is either Glc. NAc or Gal. NAc. One or both sugars contain sulfate groups (the only exception is hyaluronic acid). GAGs are highly negatively charged what is essential for their function.

Glycosaminoglycans (GAGs) Hyaluronic acid Occurence : synovial fluid, ECM of loose connective tissue Hyaluronic acid is unique among the GAGs because it does not contain any sulfate and is not found covalently attached to proteins. It forms non-covalently linked complexes with proteoglycans in the ECM. Hyaluronic acid polymers are very large (100 - 10, 000 k. D) and can displace a large volume of water.

Glycosaminoglycans (GAGs) • Hyaluronic acid (D-glucuronate + Glc. NAc) • Dermatan sulfate (L-iduronate + Glc. NAc sulfate) • Chondroitin sulfate (D-glucuronate + Gal. NAc sulfate) • Heparin and heparan sulfate (D-glucuronate sulfate + N-sulfo-Dglucosamine) • Keratan sulfate ( Gal + Glc. NAc sulfate)

GLYCOCONJUGATES

Glycoconjugates • • They are compounds that result from covalent linkages of carbohydrate molecules to both proteins and lipids. They have a profound effects on the functions of individual cells as weell as cell-cell interactions of multicellular organisms. Two classes of carbohydrate-protein conjugate: glycoproteins and proteoglycans. The glycolipids (oligosaccharide-containing lipid molecules) are found predominately on the outer surface of plasma membrane.

Glycoproteins • • Glycoprotein carbohydrate chains are highly diverse. They are formed by glycosylation and classified into two groups: 1. N-linked oligosaccharides 2. O-linked oligosaccharides The N-linked oligosaccharides have a minimum of 5 sugar residues N-linked attached to polypeptides by an N-glycosidic bond with a chain amide group of amino acid and asparagine O-linked oligosaccharides are generally short (1 -4 sugar residues) O-linked are attached to polypeptides by the side chain hydroxyl group of amino acids serine or threonine in polypeptide chains or hydroxyl groups of membrane lipids

Glycosylation • • • Glycosylation is the process or result of addition of saccharides to proteins and lipids The process plays an important role in the synthesis of membrane and secreted proteins Majority of proteins synthesized in the rough ER undergo glycosylation Two types of glycosylation exist: N-linked glycosylation to the amide nitrogen of asparagine side chains and O-linked glycosylation to the hydroxy oxygen of serine and threonine side chains. Glycosylation may play a role in cell-cell adhesion.