Carbohydrates - the biochemistry of sugars (Part II).pdf

Carbohydrates (Part II) The Biochemistry of Sugars: Monosaccharides and disaccharides Heparin segment Dr Annie Godwin ([email protected])  CHAPTER 7 Carbohydrates and Glycobiology  Checklist: what we need to know Carbohydr...

Carbohydrates (Part II) The Biochemistry of Sugars: Monosaccharides and disaccharides Heparin segment Dr Annie Godwin ([email protected])  CHAPTER 7 Carbohydrates and Glycobiology  Checklist: what we need to know Carbohydrates: Part II Key terminology 1. Introduction to monosaccharides: Carbohydrate: A sugar understanding the chemistry of (monosaccharide) or one of its dimers (disaccharide) or polymers sugars, carbonyl groups and chiral (polysaccharide). centres. 2. Understand the open-chain and ring Monosaccharide: A carbohydrate consisting of a single sugar unit. forms of monosaccharides: hemiacetals or hemiketals. Disaccharide: A carbohydrate consisting of two covalently joined 3. Understand the structures and monosaccharide units. properties of disaccharides & the glycosidic bond. Polysaccharide: A linear or 4. Understand the biological function branched polymer of monosaccharide units linked by of polysaccharides. glycosidic bonds. Monosaccharides RECAP: Aldoses & Ketoses 1 1 Monosaccharide: A carbohydrate consisting 2 2 of a single sugar unit. 3 3 Aldose: A simple sugar in which the carbonyl 4 4 carbon atom is an aldehyde; that is, the 5 5 carbonyl carbon is at one end of the carbon 6 chain. 6 Ketose: A simple monosaccharide in which the carbonyl Glucose Fructose group is a ketone. an aldose sugar a ketose sugar Monosaccharides RECAP: Chemistry of sugars Chiral center: An atom with substituents arranged so that the molecule is non superposable on its mirror image. Enantiomers: Stereoisomers that are non- superposable mirror images of each other. Fischer Projection Epimers: Two stereoisomers differing in configuration at one asymmetric center in a compound having two or more asymmetric centers. Monosaccharides: straight vs cyclic structure Glucose, Galactose & Fructose are all isomers of one another (same chemical formula, a different structural formula). In aqueous solutions aldotetroses and monosaccharides with 5 or more carbon atoms occur predominantly as cyclic structures. Haworth perspective Glucose Fructose Galactose Cyclic structure: Hemiacetals and Hemiketals Aldehyde and ketone carbons are electrophilic. Alcohol oxygen atom is nucleophilic. When aldehydes are attacked by alcohols, hemiacetals form. When ketones are attacked by alcohols, hemiketals form. Formation of additional asymmetric carbon atom (anomeric carbon) – can exist in two stereoisomeric forms. REMEMBER When two or more substituents are shown in a molecule, they are designated R1/ R2. Cyclisation of Monosaccharides There can be multiple configurations of a ring structure. Two possible ring structures for Glucose exist: α-Glucose: the isomer of glucose our body is able to use. β-glucose: an isomer of glucose our body does not recognise. Notice the difference is the placement of the hydroxyl group on Carbon 1. Cyclisation of Monosaccharides Carbonyl carbon 6 membered ring Anomers: Two = pyranoses stereoisomers of a Hydroxyl group given sugar that 5 membered ring differ only in the = furanoses configuration about Aldopyranose is the carbonyl Nucleophilic attack more stable than (anomeric) carbon on anomeric carbon aldofuranose atom. C=O becomes C-OH Hemiacetal carbon. (Reducing end) α – OH down Mutarotation β – OH up Cyclisation of Monosaccharides Ketohexoses also occur in α- and β- anomeric forms. The hydroxyl group at C-5 (or C-6) reacts with the keto group at C- 2, forming a furanose (or pyranose) ring containing a hemiketal linkage. D-Fructose’s most common anomer: β-D-fructofuranose. Cyclisation of Monosaccharides Pentoses and hexoses readily undergo intramolecular cyclisation. The former carbonyl carbon becomes a new chiral center, called the anomeric carbon (= hemiacetal or hemiketal carbon). The former carbonyl oxygen becomes a hydroxyl group; the position of this group determines if the anomer is a or b. If the hydroxyl group is on the opposite side (trans) of the ring as the CH2OH moiety the configuration is a. If the hydroxyl group is on the same side (cis) of the ring as the CH2OH moiety, the configuration is b. The hemiacetal (or hemiketal) is still reactive – it can link to another monosaccharide.. From Monosaccharides to Disaccharides Two monosaccharides bond together (dehydration reaction) to form a carbohydrate called a disaccharide. A dehydration reaction is a condensation reaction, a chemical reaction in which two molecules combine to form one single molecule, losing a small molecule in the process. The bond between two monosaccharides is known as a glycosidic bond. Disaccharide Monosaccharide Monosaccharide  The Glycosidic Bond Two sugar molecules can be joined via a glycosidic bond between an anomeric carbon and a hydroxyl carbon. The glycosidic bond (an acetal) between monomers is less reactive than the hemiacetal at the second monomer. – A second monomer, with a hemiacetal, is reducing. – The anomeric carbon involved in the glycosidic linkage is nonreducing. For example, the disaccharide formed upon condensation of two glucose molecules via carbon 1 ® 4 bond is called maltose. This is a reducing sugar (still has a free hemiacetal). Sucrose Maltose Lactose The Glycosidic Bond Maltose = glucose + glucose Hemiacetal so second residue is a reducing sugar (wavy lines indicates the structure could be a or b). Condensation results in Glycosidic bond formation à disaccharide. Reversal: Hydrolysis yields original monosaccharides. 1 2 3 4 Naming disaccharides: (1) configuration of anomeric carbon, (2) nonreducing residue (inc. furano/ pyrano – describe the ring), (3) 2 carbon atoms joined by glycosidic bond (inc. arrow), (4) name second residue (inc. furano/ pyrano). Nonreducing Disaccharides Two sugar molecules can be also joined via a glycosidic bond between two anomeric carbons. No remaining The product has two hemiacetals, acetal groups and no so these are hemiacetals. non-reducing There are no reducing disaccharides. ends, this is a nonreducing sugar. Examples: trehalose, lactose, sucrose. Carbohydrates part II: Where are we up to? 1. Monosaccharides form internal hemiacetals or hemiketals, in which the aldehyde or ketone group join with the hydroxyl group of the same molecule creating a cyclic structure (represented by Haworth perspective formula). The carbonyl carbon atom, now the anomeric carbon can assume either of two configurations: α or β (anomers – interconvertible by mutarotation). The linear form is in equilibrium with the cyclic form. 2. A hydroxyl group from a second monosaccharide can add to the anomeric carbon of the first monosaccharide (glycosidic bond) to form an acetal (protects anomeric carbon from oxidation): condensation vs hydrolysis. 3. Nomenclature for disaccharides: order of monosaccharide units, the configuration at each anomeric carbon, the carbon atoms involved in the glycosidic linkage. Definitions Acetal: An organic molecule formed by the condensation of two alcohol molecules with an aldehyde molecule (stable molecule). Anomer: Two stereoisomers of a given sugar that differ only in the configuration about the carbonyl (anomeric) carbon atom. Anomeric carbon: The carbon atom in a sugar at the new stereocenter formed when a sugar cyclizes to form a hemiacetal. This is the carbonyl carbon of aldehydes and ketones. Condensation reaction: A reaction in which two molecules combine to form a larger molecule, producing a small molecule such as H2O as a by-product. Disaccharide: A carbohydrate consisting of two covalently joined monosaccharide units. Glycosidic bond: Bonds between a sugar and another molecule (typically an alcohol, purine, pyrimidine or sugar) through an intervening oxygen. Haworth perspective formulas: A method for representing cyclic chemical structures so as to define the configuration of each substituent group; commonly used for representing sugars. Hemiacetal/ Hemiketal: Formed when an alcohol oxygen atom adds to the carbonyl carbon of an aldehyde or a ketone following nucleophilic attack (unstable intermediate). Non-reducing sugar: A carbohydrate that cannot donate electrons to other molecules and therefore cannot act as a reducing agent or be oxidized in aqueous solution. Nucleophilic addition: Initial attack of a nucleophile (hydroxyl group) on the slightly positive carbon center of the carbonyl group. Reducing sugar: A sugar in which the carbonyl (anomeric) carbon is not involved in a glycosidic bond and can therefore undergo oxidation. Cyclic monosaccharides & Disaccharides (Quiz) 1. What type of reaction is involved in the cyclization of monosaccharides? 2. What anomer configurations are formed around the hemiacetal carbon? 3. If the hydroxyl group is on the ‘cis’ side of the ring what is the configuration? 4. What is the name of the bond between two monosaccharides? 5. What type of reaction is involved in the formation of disaccharides? 6. True or False: A Hemiacetal is more stable than an Acetal. 7. What is a nonreducing disaccharide?