Carbohydrates Carbohydrates are aldehyde or ketone compounds with multiple hydroxyl groups. They make up most of the organic matter on Earth and play extensive roles in all forms of life They serve as energy stores, fuels, & metabolic intermediates Ribose & deoxyribose sugars form part of the structural framework of RNA & DNA Polysaccharides are structural elements in the cell walls of bacteria and plants. Cellulose is the most abundant organic compound in the biosphere. Carbohydrates are linked to many proteins and lipids key role in mediating interactions among cells and with other elements
Monosaccharides Simplest carbohydrates Aldehydes or ketones with two or more hydroxyl groups Empirical formula, (C-H2O)n, literally a “carbon hydrate” Important fuel molecules as well as building blocks for nucleic acid Smallest monosaccharides are trioses (n = 3) Glyceraldehyde has 1 asymmetric C 2 stereoisomers of Glyceraldehyde •(D- & L-) •are enantiomers (mirror images of each other)
Monosaccharides Monosaccharides (simple sugar molecules) can be classified according to the number of carbon atoms in the chain. Those most commonly found in humans include the following: – 3 carbons: trioses (e.g., glyceraldehyde) – 4 carbons: tetroses (e.g., erythrose) – 5 carbons: pentoses (e.g., ribose, ribulose, xylose, xylulose) – 6 carbons: hexoses (e.g., glucose, galactose, mannose, fructose)
Stereoisomers Stereoisomers are isomeric molecules that have Same molecular formula and sequence of bonded atoms (constitution) But which differ only in the three-dimensional orientations of their atoms in space Two types Enantiomers Diastereomers
Enantiomers Enantiomers are two stereoisomers that are related to each other by a reflection: – they are mirror images of each other – which are non-superimposable – Human hands are a macroscopic example of stereoisomerism S enantiomer R enantiomer
Diastereomers Diastereomers are stereoisomers – that are not enantiomers – they are distinct molecules with the same structural arrangement of atoms that are • non-superimposible • Not mirror images of each other – epimers are diastereomers that differ in configuration of only one stereogenic center 1 2 3 (2S,3S)-tartaric acid (2R,3R)-tartaric acid (2R,3S)-tartaric acid 1 and 2 are enantiomers since they are mirror images 1and 3 are diastereomers 2 and 3 are diastereomers (epimers)
Monosaccharides Simple momosaccharides with more than 3 carbon atoms – have multiple asymmetric carbon atoms – exist as diastereomers – Symbol D and L designate the absolute configuration of the asymmetric carbon farthest from the aldehyde or keto group.
D-AldosesAldehyde groupNumberingDistal asymmetric center Epimers at C2
Pentoses and Hexoses cyclize to form Furanose and Pyranose Rings Sugars in solution exist predominantly as rings and not open chains Open chain forms cyclize into rings – Aldehyde reacts with an alcohol to form hemiacetal – Ketone reacts with an alcohol to form a hemiketal
Cyclization of aldoses: pyranose For aldoses, eg glucose – C-1 aldehyde in open chain reacts with the C-5 hydroxyl group to form an intramolecular hemiacetal – Resulting six membered ring: pyranose because it resembles pyran
Cyclization of ketoses: furanose For ketoses, eg Fructose – C-2 of keto group in open chain reacts with the C-5 hydroxyl group to form an intramolecular hemiketal – Resulting five membered ring: furanose because it resembles furanHaworth Projection•Carbon atoms not shown•Plane of ring is perpendicular to the plane of screen with heavy line towards you
Fructose ring structures C5 to C2 bond C6 to C2 bond
Nomenclature of cyclic hemiacetals and hemiketals Additional asymmetric center in cyclic forms – In glucose, C-1 is the anomeric center – In fructose (furanose form), C-2 is the anomeric center • α means OH gp attached to anomeric carbon is below the plane of the ring • β means OH gp attached to anomeric carbon is above the plane of the ring C5, D C2,
Confirmation of rings Pyranose and furanose rings are not planar Pyranose: chair and boat Furanose: puckered Pyranose : Chair form favored: Steric Reasons Substituents on the ring carbon atom have 2 orientations Axial Equatorial Furanose: Puckered or envelope form C-2 endo C-2 out of the plane on the same side as C-5 C-3 endo C-3 out of the plane on the same side as C-5
Reactions of Monosaccharides React with alcohol and amines to form adducts D-glucose reacts with methanol to form – methyl-α-D-glucopyranoside – methyl-β-D-glucopyranoside – Differ in configuration at anomeric C – New bond is called glycosidic bond (anomeric C and O of hydroxyl)
Reactions of Monosaccharides The anomeric carbon can be linked to the nitrogen atom of an amine to form an N-glycosidic bond
Reducing vs. Non reducing Sugars Reducing Sugars eg., glucose – React with Fehling’s solution – Free aldehyde group is oxidized Non Reducing Sugars eg., methyl glucopyranoside – Do not react with Fehling’s solution – Not readily interconverted to a form with free aldehyde gp
Oligosaccharides Oligosaccharides are built by the linkage of 2 or more monosaccharides by O-glycosidic bonds. – Maltose • Two D-glucose residues are joined by a glycosidic linkage between – the α-anomeric form of C-1 on one sugar and – the hydroxyl oxygen atom on the C-4 of the adjacent sugar.
DisaccharidesTwo sugars joined by an O-glycosidic bond
Polysaccharides Larger polymeric oligosaccharides Play vital roles in energy storage and in maintaining the structural integrity of an organism. Homopolysaccharides : same monosaccharide – Starch – Glycogen – Cellulose – Chitin Heteropolysaccharides – Provide extracellular support – Bacterial cell wall – Cartilage and tendons
Polysaccharides: Glycogen Glycogen is highly branched polymer of glucose residues Most of the glucose units are linked by α-1,4- glycosidic bonds Branches are formed by α-1,6- glycosidic bonds Branches present about once in 10 units
Polysaccharides: Starch Two forms – Amylose • Unbranched :α-1,4- glycosidic bonds – Amylopectin • Branched; α-1,6- glycosidic bonds about every 30 units
Polysaccharides: Cellulose One of the most abundant organic compounds in the biosphere Plays structural role in plants Unbranched glucose polymer with β-1,4- glycosidic bonds Forms long straight chainsMammals lack cellulases and therefore cannot digest wood orvegetable fibers
Polysaccharide structure Structure is determined by the type of linkages – β-1,4-linkages • Straight chains • Optimal for structural purposes - α-1,4- linkages • Favor bent structure • Suitable for storage
Glycosaminoglycans:Anionic Polysaccharides Made of repeating disaccharide units Glucosamine or Galactosamine At least 1 of the sugars has a negatively charged carboxyl or sulfate group Forms proteoglycans with proteins Lubricants Structural component Mediate adhesion and bind factors stimulating cell proliferation
Enzymes: Oligosaccharide assembly Glycosyltrasferases: catalyze formation of glycosidic bonds Specific enzymes required – Specific to the sugars being linked Sugar to be added is in activated form – sugar nucleotide Proceeds with retention or inversion of configuration at glycosidic carbon atom
Human ABO Blood groups One type of blood group possess either of these structures A antigen B antigen O antigen These structures have a common oligosaccharide foundation termed O present in Oantigen A antigen has N-acetylgalactosamine addition (α-1,3- linkage to galactose moiety of Oantigen) B antigen has galactose addition (α-1,3- linkage to galactose moiety of O antigen) Specific glycosyltransferases add the extra monosaccharide to the O antigen.
Glycoproteins Carbohydrates covalently attached to proteins Small percentage of carbohydrates Components of cell membranes cell adhesion binding of sperm to egg Carbs linked to proteins through Aspargine (N-linked) Takes place in the lumen of ER and in Golgi complex Serine or threonine (O-linked) Takes place exclusively in the golgi complex
Golgi complex as sorting centerGolgi complex has 2 roles • Carbohydrate units of glycoproteins are modified • Major sorting center of the cell • Targets proteins to Lysosomes, Secretory vesicles, and Plasma membrane
Lectins: Specific carbohydrate-binding proteins• Ubiquitous • Animals, plants and microorganisms• Promote interactions between cells• In plants: can serve as potent insecticides• Binding specificities in plants is well characterized
Animal lectin Animal cell lectins facilitate cell-cell contactIn animal cell C-type lectins, Ca2+ ion links a mannose residue to the lectin
SelectinsC-type lectinsBind immune-system cells to the sites of injury Lymphocytes adhering to the lining of a lymph node
Influenza hemagglutinin•Viruses infect by binding to particular •Structures •Receptors: carbohydratesExample: Influenza virus •Binds to sialic acid residues on target cell surface through hemagglutinin • Once inside the cell, viral protein, neuraminidase, cleaves glycosidic bonds to sialic acid and frees the virus for infection. •Neuraminidase is a promising target for anti-influenza agents.