Carbohydrates PDF

Carbohydrates Structure, Function and Types  Carbohydrates are hydrates of carbon  Polyhydroxy aldehydes or ketones  Carbo are also called “Saccharides” - (Greek saccharon = sugar )  “hydrate of carbon” : composed of carbon and water and have a composition of (CH2O)n, )  Ratio - C: H: O...

Carbohydrates Structure, Function and Types  Carbohydrates are hydrates of carbon  Polyhydroxy aldehydes or ketones  Carbo are also called “Saccharides” - (Greek saccharon = sugar )  “hydrate of carbon” : composed of carbon and water and have a composition of (CH2O)n, )  Ratio - C: H: O is 1:2:1 eg: glucose - C6H12O6 / (CH2O)6 / C6(H2O) 6  Some carbohydrates also contain nitrogen, phosphorus or sulfur.  Widely distributed in both animal and plant tissues.  The most abundant constituents of living matter.  Biological importance of Carbohydrates 1. Source of energy Most commonly used - glucose. 2. Energy storing  In animals excess glucose stored as glycogen in liver and muscle / plants as starch  Starch - the major dietary carbohydrate for man  liver glycogen is used during fasting or starvation to replenish the blood glucose  Muscle, glycogen used to provide energy during exercise.  Biological importance of Carbohydrates 3. Structural function Plants : cellulose Arthropods : chitin Humans : proteoglycans, glycoproteins and glycolipids connective tissues /cell membranes Bacteria : peptidoglycans in cell membranes 4. important intermediates in various metabolic pathways eg. : Glucose-6-phosphate Glyceraldehydes – 3 – phosphate  Biological importance of Carbohydrates 5. Immunologically significant groups blood group antigens / cell surface antigens. 6. Receptor sites for hormone recognition Glycoprotein on the surface of liver /fat cells receptor for insulin. 7. Components of important compounds in the cells RNA /coenzymes - ribose & DNA - deoxyribose. 8. Medicinal importance Some antibiotics contain carbohydrates.  Classification of carbohydrates Three main groups : Monosaccharides | Disaccharides | Polysaccharides Monosaccharides Simplest sugars : can not be hydrolyzed further Disaccharides : Two monosaccharide units Oligosaccharides : 3-10 monosaccharide units Polysaccharides : Many molecules of monosaccharides  Common monosaccharides Galactose Glucose Hardly tastes sweet Mild sweet flavor Hydrolysis of lactose Known as blood sugar 1. Most have a sweet taste 2. Solids at room temperature 3. Extremely soluble in water Fructose Sweetest sugar Found in fruits and honey Added to soft drinks and deserts Importance of monosaccharides  Classification of carbohydrates Three main groups : Monosaccharides | disaccharides|polysccharides 1. Monosaccharides “Saccharide” – sakcharon- “sugar” Simple sugars / single polyhydroxy aldehyde or ketone unit Cannot be hydrolysed into smaller units Aldehydes - aldoses or ketones- ketoses Aldose Ketose Classification of monosaccharides C3 - Triose C4 - Tetrose C5 - Pentose C6 - Hexose Hexoses have different chemical composition Glucose Fructose Galactose Structure of glucose can be represented in three ways Straight Haworth Chair form chain form projection Isomerism  Identical molecular formula but different structure Structural isomerism Stereoisomerism. Structural isomerism Same formula but different structure- eg. glucose & fructose 6 CH2OH HOCH2 O CH2OH H H 5 O 4 1 OH H H HO OH OH 3 2 OH H H OH OH H Glucose (C6H12O6) Fructose (C6H12O6)  Stereoisomerism Same molecular formula & structure but different spatial arrangement of atoms The presence of asymmetric carbon atoms allow this. Asymmetric C atom is a C atom with 4 different groups attached to it Asymmetric C atom CHO CHO l l H – C – OH HO – C – H l l The spatial arrangement CH2OH of – OH is different. CH2OH In one it is on the right, Glyceraldehyde On the other it is on the (A triose) left.  Isomerism of monosaccharides  Same chemical formula but have different structures Steroisomers : monosaccharides with asymmetric carbon atoms have pair of structures that are mirror images  Isomerism of monosaccharides  Orientation of the - H and – OH groups around the carbon atom present adjacent to the carbon atom of terminal primary alcohol group Right –D Left - L  Most of the monosaccharides in mammals - D configuration  Asymmetric C atom – rotates a beam of plane of polarized light  D and L : identical in all chemical and physical properties except the direction they rotate the plane of polarized light (optical isomerism / enatiomers). Right - dextrorotatory (+) Left - levorotatory (-)  Monosaccharides form epimers  Very closely related sugars / differ in configuration of a single carbon atom other than the anomeric carbon (carbonyl carbon)  Epimers of glucose - mannose and galactose Hemiacetal & hemiketal formation H H C O + R' OH R' O C OH R R aldehyde alcohol hemiacetal R R C O + "R OH "R O C OH R' R' ketone alcohol hemiketal  Glucose forms Cyclic Structures  In aqueous solutions glucose exists in non reactive, inert cyclic conformation > 99.99 / inertness - blood glucose  The aldehyde/keto group reacts with an alcohol group on the same sugar The carbon atom which is involved in hemiacetal or acetal formation - Anomeric Carbon  Hexoses form Cyclic Structures 5- membered 6- membered furanose pyranose D- glucofuranose D- glucose D- glucopyranose D- fructofuranose D- fructose D- fructopyranose  Cyclization produces anomers Cyclization of glucose produces a new asymmetric center at C1 called anomeric C (former carbonyl C) Isomeric forms that differ only in their configuration at hemiacetal/hemiketal/anomeric c atom : anomers α: OH below the ring (α-D-glucopyranose)  β : OH above the ring (β -D-glucopyranose)  Mutarotation 36% trace 64% Chemical properties of monosaccharides Heating with strong mineral acids (H2SO4, HCL) results in the loss of water from the sugar forming a furfural derivative The furfural can condense with a napthol, thymol, resorcinol to give coloured cpds. This is the basis of: Molisch’s test Seliwanoff’s test Bial’s Tollens – phloroglucinol – HCL test  In dilute alkaline medium, both aldoses and ketoses form enediols, which are reducing. This conversion is dependent on the availability of a “FREE” aldehyde or ketone group This is the basis of Benedict’s and Fehling’s test 1 1 H H – C – OH H – C =O ll 1l l H – C – OH C – OH H – C – OH l 2 l l 2C=O H – C – OH H – C – OH l l l H – C – OH H – C – OH H – C – OH l l l H – C – OH H –5 C – OH H – C – OH l 5l 5 H – C – OH l H – C – OH H – C – OH 6 l l 6 6l H – C – OH H H l H Aldose Enediol Ketose  Oxidation of Monosaccharides  Monosaccharides oxidized by mild oxidizing agents - Cu2+ (alkaline CuSO4 - Benedict’s reagent) to form a red-orange precipitate of copper(I) oxide (Cu2O).  Carbonyl carbon oxidized to a carboxylic group.  Sugars that undergo this reaction are called reducing sugars.  Sugar acids Oxidation of Ald. Carbon / hydroxyl carbon or both. Glucose is oxidized by hypobromous acid (HOBr) to gluconic acid , glucosaccharic acid & glucuronic acid Aldhyde 1 O H – C =O O H–C=O ll l ll l 1 C – OH H – C – OH C – OH H – C – OH l l l l H – C – OH H – C – OH H – C – OH H – C – OH l l l l H – C – OH H – C – OH H – C – OH H – C – OH l l l l H – C – OH H – C – OH H – C – OH H – C – OH 5 l l l l H – C – OH H – C – OH H – C – OH C – OH 5l 6l l H – C – OH ll H C – OH O 6l ll 1ry Alcohol. H O Glucose Gluconic acid Glucosaccharic acid Glucuronic acid  Sugar Alcohols Reduction of the carbonyl carbon produce polyhydroxy alcohols Glucose Sorbitol Mannose Mannitol Fructose Sorbitol Mannitol 1CH2OH 1CH2OH l 1 CH2OH l l 2C=O H – C – OH HO – C – H 2l l l 2 H – C – OH H – C – OH H – C – OH l l Reduction Reduction l H – C – OH H – C – OH H – C – OH l l 5 l 5 H – C – OH 5 H – C – OH H – C – OH l l l 6CH2OH 6CH2OH 6 CH2OH Sorbitol Fructose Mannitol  Glycosides formation A condensation reaction between a – OH group of a monosaccharide or monosaccharide residues and a second compound that may or may not be a another monosaccharides. 1. If the second group is a hydroxyl an O-glycosidic bond is formed. 2. If the second group is an amine, and N-glycosidic bond is formed.  Ester formation  The primary or secondary alcohol groups in the sugar molecules form esters with acids.  The most important esters intermediatory metabolites in carbohydrate metabolism.  Amino sugars (Hexosamines) – OH group replaced by an amino group-amino sugars. eg: D – glucosamine, D – galactosamine , D – mannosamine CH2OH CH2OH H O H H O H H H OH H OH H OH OH OH O OH H NH2 H N C CH3 H -D-glucosamine -D-N-acetylglucosamine  Medical importance of monosaccharide i. In therapy  Glucose (dextrose) is used for intravenous feeding.  Dextrose (25% or 50%) can be injected intravenously ii. In diagnosis metabolic disturbances can be detected by estimation of urinary and blood levels of several sugars Glucose - diabetics Galactose - galactosaemia Fructose - fructose intolerance  Classification of carbohydrates 2.Disaccharides : Two monosaccharide units Sucrose = Glucose + fructose Maltose = Glucose + Glucose Lactose = Glucose + Galactose  Classification of carbohydrates 3. Oligosaccharides : 3-10 monosaccharide units The monomers of a disaccharide / polysaccharide are linked by “glycosidic bonds” When the bonding is through an oxygen atom, The glycosidic bond is called a “O” glycosidic bond. 6 CH 6 CH 2OH 2OH H H H 5 H 5 O O 4 1 4 1 H OH H OH OH O 3 2 OH 3 2 OH H OH H Glucose Glucose  Different types of glycosidic linkages Three naturally occurring glycosidic linkages: 1-4’ link: Anomeric carbon - oxygen on C4 of second sugar. 1-6’ link: Anomeric carbon - oxygen on C6 of second sugar. Reducing sugars 1-1,2’ link: Anomeric carbons of the two sugars are bonded. Non-reducing sugars  Maltose Consists of 2 glucose units in α (1-4) glycosidic bond. The anomeric C of one glucose is free. Hence it has reducing properties. 6 CH 6 CH 2OH 2OH H H H 5 H 5 O O 4 1 4 1 H OH H OH OH O 3 2 OH 3 2 OH H OH H a OH (below ring) of anomeric carbon associated with linkage 2 glucose units joined by “O-α (1-4)-glycosidic” bonds. This is maltose  Lactose The anomeric carbon of the bond comes from galactose. The anomeric carbon of glucose is free  give reducing properties. OH on anomeric C is above ring (β), hence β (1-4) 6 CH 2OH 6 CH 2OH H H 5 5 H O O 4 1 4 OH H O H 1 OH OH 3 2 H 3 2 OH H OH OH H Galactose Glucose Lactose  b (1-4) link  Sucrose with the α (1-2) link No potential aldehyde or keto group. Hence non reducing 6 CH 1 2OH O H HOCH2 H H 5 O 2 5 4 1 OH H O H HO OH 3 2 CH2OH 6 4 H OH OH H Glucose Fructose α (1-6 ) glycosidic linkage  Monosaccharides make polysaccharides Polymerization of several hundred simple sugar units. Also called glycans Differ in the length of chains / the degree of branching. Homopolysaccharides Contain only a single type of monomeric unit (eg. starch, amylose, amylopectin, cellulose, dextrins, glycogen, chitin). Heteropolysaccharides  Contain two or more different kinds of monomeric units. (eg. glycoproteins, glycolipids).  Polysaccharides Storage Structural Starch and Glycogen Cellulose, hemicellulose  Starch-composition Plants store sugar as starch / made of amylose (15 – 20%) and amylopectin (80 – 85%). Amylose  A glucose polymer with α(14) linkages. Soluble in boiling water. Unbranched polymer , 200 – 2000 glucose units Straight line / helix. Blue colour formed with iodine : due to the complex formed by iodine arranging themselves in the helix of amylose Glycemic index of a starchy food is a measure of its digestibility  Starch-composition Amylopectin  A glucose polymer with mainly α(14) linkages, but it also has branches formed by α(16) linkages.  The length of linear units in amylopectin is only 25.  α(1->4) linkage (25) to α(1->6) linkage.  The branches produce a compact structure & provide multiple chain ends CH2OH CH2OH H O H H O H amylopectin H H OH H OH H 1 O OH O H OH H OH CH2OH CH2OH 6 CH2 CH2OH CH2OH H O H H O H H 5 O H H O H H O H H H H H H OH H OH H OH H 1 4 OH H OH H 4 O O O O OH OH 2 3 H OH H OH H OH H OH H OH  Glycogen  Glucose storage polymer in animals  Similar in structure to amylopectin. Both α(1→4) glycosidic linkages and α(1→6) branch points.  Highly branched : for every 8 to 12 glucose units.  Insoluble /contribute little to the osmolarity of cytosol  The highly branched structure permits rapid glucose release from glycogen stores, e.g., in muscle during exercise.  Red/brown colour - iodine CH2OH CH2OH H O O glycogen H H H H H OH H OH H 1 O OH O H OH H OH CH2OH CH2OH 6 CH2 CH2OH CH2OH H O H H O H H 5 O H H O H H O H H H H H H OH H OH H OH H 1 4 OH H OH H 4 O O O O OH OH 2 3 H OH H OH H OH H OH H OH  Cellulose  A major constituent of plant cell walls, consists of long linear/ unbranched chains of  - D – glucopyronose units linked by   (1 4) bonds, strengthened by cross linked hydrogen bonds CH2OH 6CH OH CH2OH CH2OH CH2OH 2 O 5 O O H O H O OH H H H H H H H H OH H 1 O 4 OH H 1 O OH H O OH H O OH H OH H H H H 2 H 3 H OH H OH H OH H OH H OH  Every other glucose is flipped over, due to β linkages.  Promotes intra-chain and inter-chain H-bonds and van der Waals interactions, cause cellulose chains to be straight & rigid, and pack with a crystalline arrangement in thick bundles - microfibrils.  Microfibrils are very strong.  Role - to impart strength and rigidity to plant cell walls, can withstand high hydrostatic pressure gradients. Osmotic swelling - prevented.  Cannot be digested by many mammals - absence of a hydrolase that attacks the  - linkages.  An important sources of “bulk” in the diet.  Stimulates intestine to contract / propel the food undergoing digestion in expulsion of feces. Homopolysaccharides - single monomers Chitin  Linear polysaccharide  Structural polysaccharide of invertebrates.  Exoskeletons of crustaceans and insects.  N – acetyl – D – glucosamine units joined by  (1 4) glycosidic bonds Glycoproteins  Glycoproteins  Heteropolysaccharides  Sugars are covalently attached to peptide back bone via amino sugars (N-acetylglucosamine and N- acetylgalactosamine)  Carbohydrate chain is relatively short , often branched  May/may not be negatively charged  Almost all the plasma proteins of humans, except albumin are glycoproteins.  Glycoprotein- structure two types of glycopeptide bonds. 1. N – Glycosyl linkage 2. O - Glycosyl linkage  Glycoprotein plays a major role in the body Structural molecules Collagen, elastin, fibrins, bone, matrix Lubricants /protective agents Mucins, mucous secretions, snake venous toxins Transport molecules for Transferrin Vitamins, Lipids, Minerals Immunologic molecules Immunoglobulins, histocompatibility antigens, Hormones Chorionic gonadotrophin, Thyrotrophin Enzymes Proteases, Nucleases Cell attachment Cell – cell Recognition sites Virus – cell/ cell-cell Membrane glycoproteins Bacterium – cell, Hormone receptors Glycoproteins - mucins  Glycoproteins - mucins O – linked glycoproteins in the secretion of mucous membrane / lubricative and protective properties. Multiple COO- group of N – acetylneuramic acid / negatively charged / repel each other and prevent folding Give an extended rod like conformation / forms a viscoelastic gel Other sugars sulphated / similar properties. Function 1. Protect the mucous membranes of the respiratory gastro- intestinal and other tracts by acting as a protective barrier on the epithelial surface 2. provide lubrication. 3. The high density of oligosaccharide chains block the approach of proteases  Glycoproteins - Collagen  Protein backbone - monosaccharides and disaccharides Covalently attached to hydroxylysine in glycosidic linkage.  Only protein contain glucose as the sugar.  Carbohydrate content of collagen varies according to the type and distributions.  Glycoproteins in human blood cells Human blood group antigens Many plasma membrane proteins - glycoproteins. Eg: Glycophorin, the human red cell membrane. Contains - 60% carbohydrate.  Carbohydrate chains facing out  Blood group recognition sites.  Specificity is determined by the nature of the sugar residues in major blood groups.  Glycoproteins determines the blood type Four main blood groups. A, B, AB and O- depending on the carbohydrate residues. Face outside the cell membrane. Antigens differ from one another only in the sugar residues in peripheral portion  Glycoproteins in bacterial cell wall Bacterial cell wall polysaccharide  bacterial cell wall - long parallel polysaccharide chains cross linked to each other at intervals by short polypeptide chains.  Polysaccharide chains - alternating monosaccharide units; N– acetyl glucosamine, N–acetyl muramic acid. linked by (1 4) linkages.  Attached to each N– acetyl muramic acid unit  Lectins Carbohydrate binding proteins / bind one or more specific sugars. Tools for probing the surface of cells/ lectins recognize specific sugars exposed on the surface membrane of cells. The binding of lectin to specific sugars - agglutinating of the cells. Agglutinate cancer cells/ Showing that cancerous transformation involve alteration of the cell surface sugars  Role of carbohydrates in glycoproteins 1. Modulate physiochemical properties (solubility, viscosity charge and denaturation) Oligosaccharides are hydrophilic and increases solubility of proteins Glycoproteins : high stability to heat, detergents, acids and bases.  Role of carbohydrates in glycoproteins 2.Protein folding conformation and stabilization of biological membranes  Carbohydrates are needed for folding and acquisition of the correct conformation of certain proteins and they also participate in subunit interactions.  The presence of carbohydrate is not always essential for the particular function of glycoprotein in which it occurs.  The carbohydrate of transmembrane, glycoproteins may help to orient and anchor these molecules in the lipid bilayer.  The carbohydrate of glycoproteins, protect these molecules against proteolysis from inside and outside the cell.  Role of carbohydrates in glycoproteins 3. Biological recognition immunological determination structures of blood groups, A, B, and AB and O act as acceptors for lectins / involved in cell adhesion. 4. Involved in biologic activity eg: hormone actions 5. Target proteins to specific sub cellular locations  Proteoglycans High MW chains linked covalently to a “core protein” containing 95% carbohydrates Component of extra cellular matrix  Proteoglycans Sugar chain is long and unbranched with repeating disaccharides  Repeating disaccharides: glycosaminoglycans  Glycosaminoglycans are heteropolysaccharides containing amino sugars (hexosamine) and uronic acids.  Glycosaminoglycans covalently linked to proteins  Proteoglycans structural features High MW chains linked covalently to a protein core 3 types of proteoglycan polysaccharide - polypeptide linkages 1. O – glycosidic bond / Xyl - Ser 2. O – glycosidic bond / GalNAC -Ser (Thr) 3. N – glycosylamine bond / GlcNAC - Asn. Types of polysaccharides distinguished by a. monosaccharides composition. b. glycosidic linkage. c. amount and location of their sulfate substituent.  Glycosaminoglycans Six classes I. Hyaluronic acid II. Chondroitin sulfate III. Keratan sulfate I and II. IV. Heparin V. heparan sulfate VI. Dermatan sulfate.  Hyaluronic acid Bacteria and animal organisms / tissues Unsulfated Synovial fluid of joints Clear /Highly viscous solution Provide lubrication vitreous body of the eye Jelly like consistency to eye / glassy appearance In cartilage and tendons Tensile strength and elasticity Amino group of glucosamine is acetylated : eliminate the positive charge Contribute to compressibility  Chondroitin sulfate Cont….  Prominent component of cartilage  To maintain the neuronal shape  Associate tightly with hyaluronic acid with the aid of “link protein” to generate very large aggregates in connective tissue  GlaNAC carries a sulfate substituent in the 4 – or 6 – position  One sulfate substituent per disaccharide unit  Chondroitin sulfate  bind electrostatically each other and structural Cont…. components of matrix, collagen and elastin.  Chondritin sulphate binds to collagen and forms a cross- linked mesh giving strength and resilience to ECM  Holds the cells together and provide a porous pathway / act as a molecular sieve : for diffusion of nutrients and oxygen to individual cells  Some are polyanions and bind to polycatios which attracts water into ECM provide turgor  The structure and hydration of the ECM provide rigidity, combined with flexibility and compressibility, enabling tissue to withstand torsion and shock.  Keratan sulfate Keratan sulfate I – cornea keratan sulfate II - present along with chondroitin sulfate, attached to hyaluronic acid in loose connective tissue. In cartilage, bone and horny structures  Heparin  An important anticoagulant in blood  Stored in granules of mast cells / in intracellular  Most GlcN residues N – sulfated, few acetylated  90% of the uronic acid residues - IdUA  IdUA frequently sulfated  Protein molecule of heparin proteoglycan is unique, consisting exclusively serine and glycine residues  Heparin- functions Interactions with plasma proteins  synthesized and stored in mast cells, always in close proximity to blood vessels.  high negative charge density, interacts, strongly with several plasma components.  bind to blood clotting factors and to lipoprotein lipase present in capillary walls and cause release of triglyceride degrading enzyme into circulation.  Heparan sulfate Associated with plasma membranes. More acetylated of the GlcNAc residue, fewer N – sulfates. Act as receptors in cell growth and cell to cell communication Some cell surface heparan sulfate glycosaminoglycans - covalently linked to core proteins spanning the membrane  Dermatan sulfate  Widely distributed in skin, blood vessels, tendon and heart valves.  To maintain the overall shape of the eye  Resembles both chondroitin sulfates and heparin sulfate.  Formation - as in heparin and heapran sulfate.  Proteoglycans - functions  Provide the ground/packing substance of connective tissues  Ions draw a large quantities of water and occupy space causing swelling and stiffening the matrix  Produce a gel-like matrix that forms the body’s ground substance  Containing a large number of sulfate and carboxylate groups : gives a high density of negative charge  Induces a repulsion, forms a rod like helix / keep the carboxylic groups on alternative sides  Proteoglycans - functions  extended rod form in a solution and surrounded by a shell of water molecules  When compressed – water “squeezed out” and occupy a smaller volume and when compression released spring back to original volume due to the repulsion of the negative charges  Provides resilience, cushioning the impact between bones