Carbohydrates and Glycobiology Lecture Notes PDF

Chap 7. Carbohydrates and Glycobiology Crystal Zhang Glassford, Ph.D. Southern Adventist University Biochemistry I  Devotional thoughts Matthew 22:37 You shall love your God with all your heart, with all your soul, and with all your mind.  Carb...

Chap 7. Carbohydrates and Glycobiology Crystal Zhang Glassford, Ph.D. Southern Adventist University Biochemistry I  Devotional thoughts Matthew 22:37 You shall love your God with all your heart, with all your soul, and with all your mind.  Carbohydrates carbohydrates = aldehydes or ketones with at least two hydroxyl groups, or substances that yield such compounds on hydrolysis (polyhydroxy aldehydes or ketones) many carbohydrates have the empirical formula (CH2O)n  Classes of Carbohydrates monosaccharides = simple sugars, consist of a single polyhydroxy aldehyde or ketone unit – example: D-glucose oligosaccharides = short chains of monosaccharide units, or residues, joined by glycosidic bonds disaccharides = oligosaccharides with two monosaccharide units – example: sucrose (D-glucose and D-fructose) polysaccharides = sugar polymers with 10+ monosaccharide units – examples: cellulose (linear), glycogen (branched) 7.1 Monosaccharides and Disaccharides  The Two Families of Monosaccharides Are Aldoses and Ketoses aldose = carbonyl group at an end of the carbon chain (in an aldehyde group) ketose = carbonyl group at any other position (in a ketone group) trioses hexoses pentoses backbones of monosaccharides: unbranched carbon chains with single bonds linking all carbon atoms one of the carbon atoms is double-bonded to an oxygen atom to form a carbonyl group other carbon atoms are bonded to a hydroxyl group Monosaccharides Have Asymmetric Centers all monosaccharides (except dihydroxyacetone) contain 1+ chiral carbon atom – occur in optically active isomeric forms enantiomers = two different optical isomers that are mirror images in general, a molecule with n chiral centers can have 2n stereoisomers  Fischer Projection Formulas used to represent three- dimensional sugar structures on paper bonds drawn horizontally indicate bonds that project out of the plane of the paper bonds drawn vertically project behind the plane of the paper  D Isomers and L Isomers reference carbon = chiral center most distant from the carbonyl carbon two groups of stereoisomers: – D isomers = configuration at reference carbon is the same as D-glyceraldehyde on the right (dextro) in a projection formula most hexoses of living organisms – L isomers = configuration at reference carbon is the same as L-glyceraldehyde on the left (levo) in a projection formula  D-Aldoses * * * * * *those are the ones you need to know Fisher Projections  D-Ketoses *those are the ones you * need to know Fisher Projections *  Epimers epimers = two sugars that differ only in the configuration around one carbon atom carbons are numbered beginning at the end of the chain near the carbonyl group  The Common Monosaccharides Have Cyclic Structures in aqueous solution, aldotetroses and all monosaccharides with 5+ backbone carbon atoms occur as cyclic structures – covalent bond between the carbonyl group and the oxygen of a hydroxyl group  Hemiacetals and Hemiketals hemiacetals or hemiketals = derivatives formed by a general reaction between alcohols and aldehydes or ketones – product of the first alcohol molecule addition – a five- or six-membered ring forms if the —OH and carbonyl groups are on the same molecule acetal or ketal = product of the second alcohol molecule addition – forms a glycosidic bond Formation of Hemiacetals and Hemiketals  α and β Stereoisomeric Configurations reaction with the first alcohol molecule creates an additional chiral center (the carbonyl carbon) produces either of two stereoisomeric configurations: α and β anomers = isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or hemiketal carbon atom anomeric carbon = the carbonyl carbon atom Formation of the Two Cyclic Forms of D-Glucose reaction between the aldehyde group at C-1 and the hydroxyl group at C- 5 forms a hemiacetal linkage mutarotation = the interconversion of α and β anomers  Pyranoses and Furanoses pyranoses = six-membered ring compounds – form when the hydroxyl group at C-5 reacts with the keto group at C-1 furanoses = five-membered ring compounds – form when the hydroxyl group at C-5 reacts with the keto group at C-2  Haworth Perspective Formulas Haworth perspective formulas = more accurate representation of cyclic sugar structure than Fischer projections – six-membered ring is tilted to make its plane almost perpendicular to that of the paper – bonds closest to the reader are drawn thicker than those farther away Converting D-Hexose Fischer Projections to Haworth Perspective Formulas step 1: draw the six-membered ring (five carbons, and one oxygen at the upper right) step 2: number the carbons in a clockwise direction beginning with the anomeric carbon step 3: place the hydroxyl groups – hydroxyl groups on the right in a Fischer projection are placed pointing down and those on the left are placed pointing up step 4: place the terminal —CH2OH group – projects upward for the D enantiomer, downward for the L enantiomer step 5: place the anomeric hydroxyl group – for a β structure, the hydroxyl group is placed on the same side of the ring as C-6 – for an α structure, it is placed on the opposite side Organisms Contain a Variety of Hexose Derivatives Identifying hexose derivatives is required!  Aldonic and Uronic Acids aldonic acids = form following oxidation of the carbonyl carbon of aldoses uronic acids = form following oxidation at C-6 both form stable intramolecular esters called lactones  Phosphorylated Derivatives some sugar intermediates are phosphate esters – example: glucose 6-phosphate stable at neutral pH and bear a negative charge functions to trap sugar inside the cell because most cells do not have membrane transporters for phosphorylated sugars  Sugars That Are, or Can Form, Aldehydes Are Reducing Sugars reducing sugars = undergo a characteristic redox reaction where free aldehyde groups react with Cu2+ under alkaline condition – reduction of Cu2+ to Cu+ forms a brick-red precipitate ketoses that can tautomerize to form aldehydes are also reducing sugars  Formation of Maltose O-glycosidic bond = covalent linkage joining two monosaccharides – formed when a hydroxyl group of one sugar molecule reacts with the anomeric carbon of the other – readily hydrolyzed by acid formation of a glycosidic bond renders a sugar nonreducing reducing end = the end of a disaccharide or polysaccharide chain with a free anomeric Free anomeric carbon carbon Naming Reducing Oligosaccharides step 1: with the nonreducing end on the left, give the configuration (α or β) at the anomeric carbon joining the first unit to the second step 2: name the nonreducing residue using “furano” or “pyrano” step 3: indicate in parentheses the two carbon atoms joined by the glycosidic bond, with an arrow connecting the two numbers step 4: name the second residue and repeat for additional residues  Symbols and Abbreviations for Monosaccharides and Derivatives  Three Common Disaccharides lactose is a reducing disaccharide sucrose and trehalose are nonreducing sugars  Reducing sugar A reducing sugar is any sugar that is capable of acting as a reducing agent. In an alkaline solution, a reducing sugar forms some aldehyde or ketone, which allows it to act as a reducing agent, in Benedict's reagent, the sugar becomes a carboxylic acid. Ketoses must first tautomerize to aldoses before they can act as reducing sugars. The common dietary monosaccharides: – galactose, glucose and fructose are all reducing sugars. Disaccharides: - Nonreducing: sucrose and trehalose; have glycosidic bonds between their anomeric carbons and thus cannot convert to an open-chain form with an aldehyde group; they are stuck in the cyclic form. - Reducing: lactose and maltose; have only one of their two anomeric carbons involved in the glycosidic bond, while the other is free and can convert to an open-chain form with an aldehyde group. https://en.wikipedia.org/wiki/Reducing_sugar Learning objectives  7.2 Polysaccharides & 7.3-1 Glycoconjugates  Devotional thoughts Micah 7:18 Who is a God like You, pardoning iniquity and passing over the transgression of the remnant of His heritage? He does not retain His anger forever, because He delights in mercy.  Polysaccharides most carbohydrates in nature occur as polysaccharides (Mr > 20,000) also called glycans  Homopolysaccharides and Heteropolysaccharides homopolysaccharides = contain only a single monomeric sugar species – serve as storage forms and structural elements heteropolysaccharides = contain 2+ kinds of monomers – provide extracellular support Polysaccharides Generally Do Not Have Defined Lengths or Molecular Weights this distinction between proteins and polysaccharides is a consequence of the mechanisms of assembly there is no template for polysaccharide synthesis the program for polysaccharide synthesis is intrinsic to the enzymes that catalyze the polymerization of monomer units Some Homopolysaccharides Are Storage Forms of Fuel storage polysaccharides = starch in plant cells and glycogen in animal cells starch and glycogen molecules are heavily hydrated because they have many exposed hydroxyl groups available to hydrogen bond  Starch and Glycogen starch = contains two types of glucose polymer, amylose and amylopectin – amylose = long, unbranched chains of D-glucose residues connected by (α1→4) linkages – amylopectin = larger than amylose with (α1→4) linkages between glucose residues and highly branched due to (α1→6) linkages glycogen = polymer of (α1→4)-linked glucose subunits, with (α1→6)-linked branches – more extensively branched – more compact than starch  Structure of Starch and Glycogen Amylose (plants) and glycogen (animal) Amylopectin or glycogen Storage of Glucose as Polymers Avoids High Osmolarity hepatocytes in the fed state store glycogen equivalent to a glucose concentration of 0.4 M 0.4 M glucose in the cytosol would elevate the osmolarity – the resulting osmotic entry of water might rupture the cell Q: Why is it logical for sugars to be added to only one end of glycogen, making them excellent molecules for glucose storage? Answer: Because there are many nonreducing ends on one molecule, allowing rapid glucose storage and release. Some Homopolysaccharides Serve Structural Roles cellulose = tough, fibrous, water-insoluble substance – linear, unbranched homopolysaccharide, consisting of 10,000 to 15,000 D-glucose units – glucose residues have the β configuration – linked by (β1→4) glycosidic bonds – animals do not have the enzyme to hydrolyze (β1→4) glycosidic bonds  Chitin chitin = linear homopolysaccharide composed of N- acetylglucosamine residues in (β1→4) linkage – acetylated amino group makes chitin more hydrophobic and water-resistant than cellulose  Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding three-dimensional structures stabilized by weak interactions within or between molecules – hydrogen bonding is especially important due to the high number of hydroxyl groups in polysaccharides free rotation about both C—O bonds linking the residues is limited by steric hindrance by substituents Different Energetic Conformation of a Disaccharide bulkiness and electronic effects at the anomeric carbon place constraints on φ and ψ  Helical Structure of Starch and Glycogen most stable three- dimensional structure for the (α1→4)-linked chains of starch and glycogen – six residues/turn Shown as blue in iodine test amylopectin  Linear Structure of Cellulose most stable conformation is a straight, extended chain – each chair is turned 180° relative to its neighbors Q: most animals cannot use Found in cell walls of plants cellulose as fuel source. Explain why?  Peptidoglycan Reinforces the Bacterial Cell Wall peptidoglycan = rigid component of bacterial cell walls – heteropolymer of alternating (β1→4)- linked N- acetylglucosamine and N-acetylmuramic acid residues – cross-linked by short peptides  Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix extracellular matrix (ECM) = gel-like material in the extracellular space of tissues that holds cells together and provides a porous pathway for nutrient and O2 diffusion – composed of an interlocking meshwork of heteropolysaccharides (ground substance) and fibrous proteins basement membrane (specialized ECM) also contains heteropolysaccharides  Repeating Units of Glycosaminoglycans of ECM glycosaminoglycans = heteropolysaccharides in ECM – linear polymers composed of repeating disaccharide units – one monosaccharide is always either N-acetylglucosamine or N-acetylgalactosamine and the other is usually a uronic acid – unique to animals and bacteria – some contain esterified sulfate groups  Types of Glycosaminoglycans hyaluronan (hyaluronic acid) = alternating residues of D-glucuronic acid and N-acetylglucosamine chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate differ from hyaluronan in three respects: – generally much shorter polymers – covalently linked to specific proteins (proteoglycans) – one or both monomer units differ from hyaluronan provide viscosity, adhesiveness, and tensile strength to the extracellular matrix  Heparan Sulfate contains variable, nonrandom arrangements of sulfated and nonsulfated sugars sulfated residues gives the molecule the ability to interact specifically with proteins Heparin – highly sulfated, intracellular form of heparan sulfate produced primarily by mast cells – used as a therapeutic agent to inhibit coagulation of blood through its capacity to bind the protease inhibitor antithrombin  Structure and Roles of Some Polysaccharides Table 7-2 Structures and Roles of Some Polysaccharides Polymer Type Repeating unit Size (number of Roles/significance monosaccharide units) Starch: Homo- (𝛼1→4)Glc, 50-5,000 Energy storage: in plants Amylose linear Starch: Homo- (𝛼1→4)Glc, Up to 106 Energy storage: in plants Amylopectin with (𝛼1→6)Glc branches every 24-30 residues Glycogen Homo- (𝛼1→4)Glc, Up to 50,000 Energy storage: in bacteria and animal with (𝛼1→6)Glc cells branches every 8-12 residues Cellulose Homo- (𝛽1→4)Glc Up to 15,000 Structural: in plants, gives rigidity and strength to cell walls Chitin Homo- (𝛽1→4)GlcNAc Very large Structural: in insects, spiders, crustaceans, gives rigidity and strength to exoskeletons Dextran Homo- (𝛼1→6)Glc, Wide range Structural: in bacteria, extracellular with (𝛼1→3) adhesive branches Peptidoglycan Hetero-; peptides 4)Mur2Ac(𝛽1→4) Very large Structural: in bacteria, gives rigidity and attached GlcNAc (𝛽1 strength to cell envelope Hyaluronan (a glycosaminoglycan) Hetero-; acidic 4)GlcA(𝛽1→3) Up to 100,000 Structural: in vertebrates, extracellular GlcNAc (𝛽1 matrix of skin and connective tissue; viscosity and lubrication in joints  Glycoconjugate glycoconjugate = biologically active molecule consisting of an informational carbohydrate joined to a protein or lipid  Proteoglycans proteoglycans = macromolecules of the cell surface or ECM consisting of 1+ sulfated glycosaminoglycan chain(s) joined covalently to a membrane protein or secreted protein – major component of all extracellular matrices  Glycoproteins glycoproteins = have one or several oligosaccharides joined covalently to a protein – found on the outer face of the plasma membrane, in ECM, in blood, and in organelles (Golgi complexes, secretory granules, and lysosomes) – oligosaccharide portions are heterogenous and rich in information Glycolipids and Glycosphingolipids glycolipids = plasma membrane components in which the hydrophilic head groups are oligosaccharides glycosphingolipids = class of glycolipids with specific backbone structure – neurons are rich in glycosphingolipids – play a role in signal transduction Learning objectives