BCH3033 Biochemistry 1 Chapter 7b PDF

BCH3033: Biochemistry 1 Chapter 7b 02.29.2024 Donella Beckwith, Ph.D. [email protected] 1 Aldonic and Uronic Acids aldose aldonic acids = form following oxidation of the carbonyl carbon of aldoses – aldehyde of an aldose is oxidized – In glucose, oxidation occurs at C1 uronic acids = form following...

BCH3033: Biochemistry 1 Chapter 7b 02.29.2024 Donella Beckwith, Ph.D. [email protected] 1 Aldonic and Uronic Acids aldose aldonic acids = form following oxidation of the carbonyl carbon of aldoses – aldehyde of an aldose is oxidized – In glucose, oxidation occurs at C1 uronic acids = form following oxidation at C-6 – the terminal –OH of an aldose or ketose is oxidized – both steps can happen directly from glucose under STRONG oxidation conditions both form stable intramolecular esters called lactones (cyclic versions of the acids above) 2 Polysaccharides most carbohydrates in nature occur as polysaccharides (Mr > 20,000) Can also be called glycans: – are carbohydrates linked by a glycosidic bond Differ from each other in: – the identity of their recurring monosaccharide units – chain length – type of bonds linking the units – degree of branching 3 Homopolysaccharides and Heteropolysaccharides homopolysaccharides = contain only a single monomeric sugar species – serve as storage forms and structural elements (Ex: animal exoskeletons) heteropolysaccharides = contain 2 or more kinds of monomers – provide extracellular support 4 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 5 Question Which statement is false regarding homopolysaccharides and heteropolysaccharides? A. Homopolysaccharides contain a single monomeric sugar species. B. Some homopolysaccharides serve as structural elements in animal exoskeletons. C. Heteropolysaccharides serve as storage forms of monosaccharides that are used as fuel. D. In animal tissues, the extracellular space is occupied by several types of heteropolysaccharides. 6 Some Homopolysaccharides Are Storage Forms of Fuel storage polysaccharides: – Starch: in plant cells – Glycogen: in animal cells Starch and glycogen molecules are heavily hydrated because they have many exposed hydroxyl groups available to hydrogen bond 7 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 8 Structure of Starch and Glycogen D-Glucose 9 Question What O-glycosidic bond is commonly found in amylose, amylopectin, and glycogen? A. B. C. D. (β14) (α16) (β16) (α14) 10 Question A glycogen molecule with 28 branches has how many nonreducing and reducing ends? A. B. C. D. 28 nonreducing ends and 28 reducing ends 29 nonreducing ends and 1 reducing end 1 nonreducing end and 29 reducing ends 1 nonreducing end and 1 reducing end 11 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 n 12 Question Even though amylose and cellulose are made of similar homopolysaccharide chains, they have very different properties. Why? A. The β-glycosidic linkage of glucose molecules in cellulose form interchain and intrachain hydrogen bonds that produce straight, stable fibers that exclude water. B. Cellulose is composed of galactose, while amylose is composed of glucose. C. The α-glycosidic linkage of glucose molecules in amylose causes it to form helices that exclude water. D. Amylose makes a linear polymer which cannot make 13 hydrogen bonds. Chitin chitin = linear homopolysaccharide composed of Nacetylglucosamine residues in (β1→4) linkage – acetylated amino group makes chitin more hydrophobic and water-resistant than cellulose Example: Spotted June beetle whose exoskeleton is made of chitin 14 Question Why are chitin and cellulose hydrophobic and essentially insoluble in an aqueous media? A. Because polymers of these molecules pack so tightly together, there is no geometric space left for water. B. Because they form many internal hydrogen bonds, they leave no sites for binding to water. C. Because there are no enzymes that can break the beta linkages. D. Because the linear polymer cannot make hydrogen bonds. 15 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 (glycosidic bonds) is limited by steric hindrance by substituents 16 Helical Structure of Starch and Glycogen Is the most stable three-dimensional structure for the (α1→4)-linked chains of starch and glycogen – six sugar residues per turn 17 Linear Structure of Cellulose most stable conformation is a straight, extended chain – each chair is turned 180° relative to its neighbors – each residue involved in 2 hydrogen bonds 18 Peptidoglycan Reinforces the Bacterial Cell Wall peptidoglycan = rigid component of bacterial cell walls – heteropolymer of alternating (β1→4)linked Nacetylglucosamine and N-acetylmuramic acid residues – cross-linked by short peptides 19 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 20 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 21 Types of Glycosaminoglycans hyaluronan (hyaluronic acid) = has 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 22 Question Which characteristic is NOT one that is true of glycosaminoglycans? A. B. C. D. found in extracellular matrix always contain sulfates are heteropolysaccharides are disaccharide repeat units 23 Question The glycosaminoglycan hyaluronan: A. is a homopolysaccharide. B. consists of alternating residues of D-glucuronic acid and Nacetylglucosamine. C. is covalently linked to specific proteins. D. is a much shorter polymer than heparin. 24 Heparan Sulfate/ Heparan contains variable, nonrandom arrangements of sulfated and nonsulfated sugars sulfated residues gives the molecule the ability to interact specifically with proteins 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 25 Glycoconjugate glycoconjugate = biologically active molecule consisting of an informational carbohydrate covalently linked to a protein or lipid 26 Proteoglycans proteoglycans = macromolecules of the cell surface or ECM consisting of 1 or more sulfated glycosaminoglycan chain(s) joined covalently to a membrane protein or secreted protein – major component of all extracellular matrices 27 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 28 Glycolipids and Glycosphingolipids glycolipids = are plasma membrane components in which the hydrophilic head groups are oligosaccharides glycosphingolipids = are a class of glycolipids with specific backbone structure – neurons are rich in glycosphingolipids – play a role in signal transduction 29 Question Which statement about glycoconjugates is false? A. The glycosaminoglycan chain of the proteoglycan can bind to extracellular proteins through electrostatic interactions. B. Glycolipids are found in specific organelles, such as Golgi complexes. C. Glycosphingolipids play a role in signal transduction. D. The oligosaccharide portions of glycoproteins are very heterogeneous. 30 Proteoglycans Are GlycosaminoglycanContaining Macromolecules of the Cell Surface and Extracellular Matrix proteoglycan unit is the “core protein” with covalently attached glycosaminoglycan(s) tetrasaccharide linker “bridge” connects a glycosaminoglycan to a Ser residue of the protein 31 Question Which statement about proteoglycans is false? A. B. C. D. They contain protein. They can affect ligand-receptor interactions. They are always extracellular. They contain glycosaminoglycans. 32 Heparan Sulfate Enhancement of the Binding of Thrombin to Antithrombin antithrombin binds to and inhibits the protease thrombin only in the presence of heparan sulfate both proteins are rich in Arg and Lys residues (positively charged) – interact electrostatically with the sulfates (negatively charged) of heparan sulfate Positively charged regions 33 Proteoglycan Aggregates proteoglycan aggregates = supramolecular assemblies of many core proteins all bound to a single molecule of hyaluronan aggrecan Mr~250,0002x106 aggrecan interacts strongly with collagen in the ECM of cartilage – contributes to strength and resilience of connective tissue 34 Fibronectin and Integrins fibronectin = has separate domains to bind fibrin, heparan sulfate, and collagen – contain the conserved RGD sequence (Arg– Gly–Asp) to bind integrins integrins = mediate signaling between cell interior and ECM molecules 35 Purpose of Interactions between Cells and the ECM interactions between cells and the ECM: – anchor cells to the ECM, providing the strength and elasticity of skin and joints – provide paths that direct the migration of cells in developing tissue – convey information in both directions across the plasma membrane 36 Glycoproteins Have Covalently Attached Oligosaccharides two types of attachments: – O-linked = a glycoside bond joins the anomeric carbon of a carbohydrate to the —OH of a Ser or Thr residue – N-linked = an N-glycosyl bond joins the anomeric carbon of a sugar to the amide nitrogen of an Asn residue 37 Question A laboratory is studying the binding properties of a glycoprotein on the plasma membrane. What amino acids should they analyze for the presence of branched heteropolysaccharides? A. B. C. D. Ser, Thr, and Tyr Ser, Thr, and Asn Trp, Tyr, and Phe Lys, His, and Arg 38 Examples of Glycoproteins mucins = secreted or membrane glycoproteins – can contain large numbers of O-linked oligosaccharide chains – present in most secretions proteins of the blood – examples: immunoglobulins (antibodies), folliclestimulating hormone, luteinizing hormone, and thyroid-stimulating hormone milk proteins – example: major whey protein α-lactalbumin 39 Glycomics glycomics = the systematic characterization of all carbohydrate components of a given cell or tissue, including those attached to proteins and to lipids The Biological Advantages of Adding Oligosaccharides to Proteins covalently attached oligosaccharides: – influence the folding and stability of the proteins – provide critical information about the targeting of newly synthesized proteins – allow specific recognition by other proteins 40 Question Glycoproteins: A. contain unbranched oligosaccharides. B. are sometimes intracellular. C. have oligosaccharides covalently attached to aspartate residues. D. are a small fraction of the total number of proteins in a human cell. 41 Glycolipids and Lipopolysaccharides Are Membrane Components gangliosides = membrane lipids of eukaryotic cells in which the polar head group is a complex oligosaccharide containing a sialic acid and other monosaccharide residues lipopolysaccharides = dominant surface feature of the outer membrane of gram-negative bacteria 42 Question Which of these is NOT a glycoconjugate? A. B. C. D. trehalose syndecan glypican glycosphingolipid 43 Question Oligosaccharides are: A. B. C. D. never found in mucins. classified as a N- or O-linked when found in gangliosides. found in bacterial lipopolysaccharides. never attached to hormones. 44 The Challenge of Glycobiology glycobiology = the study of the structure and function of glycoconjugates the challenge is to understand how cells use specific oligosaccharides to encode information about: – intracellular targeting of proteins – cell-cell interactions – cell differentiation and tissue development – extracellular signals 45 Oligosaccharide Structures Are Information-Dense branched structures, not found in nucleic acids or proteins, are common in oligosaccharides almost limitless variety of oligosaccharides due to differences in: – stereochemistry and position of glycosidic bonds – type and orientation of substituent groups – the number and type of branches 46 Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes lectins = bind carbohydrates with high specificity and with moderate to high affinity functions: – cell-cell recognition – signaling – adhesion – intracellular targeting of newly synthesized proteins 47 Selectins selectins = family of plasma membrane lectins that mediate cell-cell recognition and adhesion in a wide range of cellular processes – move immune cells through the capillary wall – mediate inflammatory responses – mediate the rejection of transplanted organs 48 Question Which statement about selectins is false? A. They mediate cell-cell recognition. B. They are involved in the movement of immune system cells. C. They can be involved in the process rejection of transplanted organs. D. They are intracellular. 49 Lectin-Carbohydrate Interactions Are Highly Specific and Often Multivalent subtle molecular complementarity allows interaction only with the lectin’s correct carbohydrate binding partners lectin multivalency = single lectin molecule has multiple carbohydrate binding domains increases effective affinity 50 Interactions of Sugar Residues Due to the Hydrophobic Effect many sugars have a more polar side and a less polar side affords specificity in binding between the sugar and the lectin and sometimes affords high affinity 51 Question Lectins: A. B. C. D. often bind their ligands via multiple weak interactions. bind their ligands with relatively low specificity. prevent viruses from binding to their target cells. are carbohydrates that bind to receptor proteins. 52 Important Sugars to be Familiar with for Exam 2 Structures in all projections: Fischer, Haworth, and Conformational (Chair), anomers Functional group differences Naming in polysaccharides Galactose (Gal) Glucose (Glu) N-acetylgalactosamine (GalNAc) N-acetylglucosamine (GlcNAc) 53